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Sample records for macromolecular host-guest complexes

  1. Mechanism of host-guest complexation by cucurbituril.

    Science.gov (United States)

    Márquez, César; Hudgins, Robert R; Nau, Werner M

    2004-05-12

    The factors affecting host-guest complexation between the molecular container compound cucurbit[6]uril (CB6) and various guests in aqueous solution are studied, and a detailed complexation mechanism in the presence of cations is derived. The formation of the supramolecular complex is studied in detail for cyclohexylmethylammonium ion as guest. The kinetics and thermodynamics of complexation is monitored by NMR as a function of temperature, salt concentration, and cation size. The binding constants and the ingression rate constants decrease with increasing salt concentration and cation-binding constant, in agreement with a competitive binding of the ammonium site of the guest and the metal cation with the ureido carbonyl portals of CB6. Studies as a function of guest size indicate that the effective container volume of the CB6 cavity is approximately 105 A(3). It is suggested that larger guests are excluded for two reasons: a high activation barrier for ingression imposed by the tight CB6 portals and a destabilization of the complex due to steric repulsion inside. For example, in the case of the nearly spherical azoalkane homologues 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH, volume ca. 96 A(3)) and 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO, volume ca. 110 A(3)), the former forms the CB6 complex promptly with a sizable binding constant (1300 M(-1)), while the latter does not form a complex even after several months at optimized complexation conditions. Molecular mechanics calculations are performed for several CB6/guest complexes. A qualitative agreement is found between experimental and calculated activation energies for ingression as a function of both guest size and state of protonation. The potential role of constrictive binding by CB6 is discussed.

  2. Carbohydrate-Based Host-Guest Complexation of Hydrophobic Antibiotics for the Enhancement of Antibacterial Activity.

    Science.gov (United States)

    Jeong, Daham; Joo, Sang-Woo; Shinde, Vijay Vilas; Cho, Eunae; Jung, Seunho

    2017-08-08

    Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of cyclodextrins, cyclosophoraoses, and some linear oligosaccharides, are generally used as host complexation agents in drug delivery systems. Many antibiotics with low bioavailability have some limitations to their clinical use due to their intrinsically poor aqueous solubility. Bioavailability enhancement is therefore an important step to achieve the desired concentration of antibiotics in the treatment of bacterial infections. Antibiotics encapsulated in a complexation-based drug delivery system will display improved antibacterial activity making it possible to reduce dosages and overcome the serious global problem of antibiotic resistance. Here, we review the present research trends in carbohydrate-based host-guest complexation of various hydrophobic antibiotics as an efficient delivery system to improve solubility, permeability, stability, and controlled release.

  3. SANS contrast variation on a dendrimer host-guest complex

    NARCIS (Netherlands)

    Kleppinger, R.; Mortensen, K.; Meijer, E.W.

    2002-01-01

    Small-angle neutron scattering (SANS) technique was used to study the configurational changes in an oligoethyleneoxy-functionalized poly(propyleneimine) dendrimer (host) when forming complexes with rose bengal (guest). Guinier fits to the scattering data recorded at max. contrast indicated a

  4. Host-guest complexes between cucurbit[n]urils and acetanilides having aminopropyl units.

    Science.gov (United States)

    Buaki-Sogo, Mireia; Montes-Navajas, Pedro; Alvaro, Mercedes; Garcia, Hermenegildo

    2013-06-01

    2-(Propylamino)acetamide of aniline (1a), and bis-2-(propylamino)acetamide of ortho- (1b) and para-(1c) phenylenediamine form host-guest complexes with CB[6], CB[7] and CB[8] as evidenced by the variations in the (1)H NMR spectroscopy chemical shifts and observation in MALDI-TOF-MS and ESI-MS of ions at the corresponding mass. Binding constants for the 1:1 complexes were estimated from fluorescence titrations and were in the range 10(5)-10(6)M(-1). Models based on molecular mechanics for these supramolecular complexes are provided. In spite of the different geometries arising from the ortho- or para-substitution, phenylenediamides form complexes of similar strength in which the hydrophobic alkyl chains are accommodated inside the host cavity. Formation of these host-guest complexes in the solid state was also achieved by modifying an aminopropyl silica with chloroacetanilides and preparing three silica having analogues of compounds 1a-c anchored to the solid particles. Titrations showed, however, that these solids can adsorb a large percentage of CBs by unselective interactions that are not related to the formation of inclusion complexes. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Hydrogen bonding assemblies in host guest complexes with 18-crown-6

    Science.gov (United States)

    Fonari, M. S.; Simonov, Yu. A.; Kravtsov, V. Ch.; Lipkowski, J.; Ganin, E. V.; Yavolovskii, A. A.

    2003-02-01

    Recent X-ray crystal structural data for two novel 1:2 host-guest complexes of 18-crown-6 with neutral organic molecules, thiaamide hydrazide of 2-aminobenzoic acid and thiaamide hydrazide of 4-amino-1,2,5-thiadiazole-3-carbonic acid are reported. The supramolecular structures of these two and five relative complexes are discussed from the point of view of participation of donor groups in coordination with the crown ether, and donor and acceptor groups in the self-assembly of the guest molecules. Guest molecules have incorporated amine and hydrazine moieties as proton donors and carbonyl oxygen and sulfur (in thiadiazole and in thiaamine moieties) as proton acceptors. The guest-guest interactions appeared to be crucial in the final architecture.

  6. Host-Guest Interaction of Cucurbit[8]uril with N-(3-Aminopropyl)cyclohexylamine: Cyclohexyl Encapsulation Triggered Ternary Complex.

    Science.gov (United States)

    Xia, Yu; Wang, Chuan-Zeng; Tian, Mengkui; Tao, Zhu; Ni, Xin-Long; Prior, Timothy J; Redshaw, Carl

    2018-01-15

    The host-guest interaction of a series of cyclohexyl-appended guests with cucurbit[8]uril (Q[8]) was studied by ¹H NMR spectroscopy, isothermal titration calorimetry (ITC), and X-ray crystallography. The X-ray structure revealed that two cycloalkane moieties can be simultaneously encapsulated in the hydrophobic cavity of the Q[8] host to form a ternary complex for the first time.

  7. Host-Guest Interaction of Cucurbit[8]uril with N-(3-Aminopropylcyclohexylamine: Cyclohexyl Encapsulation Triggered Ternary Complex

    Directory of Open Access Journals (Sweden)

    Yu Xia

    2018-01-01

    Full Text Available The host-guest interaction of a series of cyclohexyl-appended guests with cucurbit[8]uril (Q[8] was studied by 1H NMR spectroscopy, isothermal titration calorimetry (ITC, and X-ray crystallography. The X-ray structure revealed that two cycloalkane moieties can be simultaneously encapsulated in the hydrophobic cavity of the Q[8] host to form a ternary complex for the first time.

  8. Investigation of the host-guest complexation between 4-sulfocalix[4]arene and nedaplatin for potential use in drug delivery

    Science.gov (United States)

    Fahmy, Sherif Ashraf; Ponte, Fortuna; Abd El-Rahman, Mohamed K.; Russo, Nino; Sicilia, Emilia; Shoeib, Tamer

    2018-03-01

    Macromolecules including macrocyclic species have been reported to have the potential to encapsulate biologically active compounds such as drugs through host-guest complexation to increase their solubility, stability and bioavailability. In this paper the first experimental and theoretical investigation of the complexation between nedaplatin, a second generation antineoplastic drug, and p-4-sulfocalix[4]arene, a macromolecule possessing a bipolar amphiphilic structure with good biocompatibility and relatively low haemolytic toxicity for potential use as a drug delivery system is presented. Data from 1H NMR, UV, Job's plot analysis, HPLC and DFT calculations are detailed and suggest the formation of a 1:1 complex. The stability constant of the complex was experimentally estimated to be 3.6 × 104 M- 1 and 2.1 × 104 M- 1 which correspond to values of - 6.2 and - 5.9 kcal mol- 1, respectively for the free energy of complexation while the interaction free energy is calculated to be - 4.9 kcal mol- 1. The formed species is shown to be stabilised in solution through hydrogen bonding between the host and the guest which may allow for this strategy to be effective for potential use in drug delivery.

  9. Through-Space Paramagnetic NMR Effects in Host-Guest Complexes: Potential Ruthenium(III) Metallodrugs with Macrocyclic Carriers.

    Science.gov (United States)

    Chyba, Jan; Novák, Martin; Munzarová, Petra; Novotný, Jan; Marek, Radek

    2018-04-05

    The potential of paramagnetic ruthenium(III) compounds for use as anticancer metallodrugs has been investigated extensively during the past several decades. However, the means by which these ruthenium compounds are transported and distributed in living bodies remain relatively unexplored. In this work, we prepared several novel ruthenium(III) compounds with the general structure Na + [ trans-Ru III Cl 4 (DMSO)(L)] - (DMSO = dimethyl sulfoxide), where L stands for pyridine or imidazole linked with adamantane, a hydrophobic chemophore. The supramolecular interactions of these compounds with macrocyclic carriers of the cyclodextrin (CD) and cucurbit[ n]uril (CB) families were investigated by NMR spectroscopy, X-ray diffraction analysis, isothermal titration calorimetry, and relativistic DFT methods. The long-range hyperfine NMR effects of the paramagnetic guest on the host macrocycle are related to the distance between them and their relative orientation in the host-guest complex. The CD and CB macrocyclic carriers being studied in this account can be attached to a vector that attracts the drug-carrier system to a specific biological target and our investigation thus introduces a new possibility in the field of targeted delivery of anticancer metallodrugs based on ruthenium(III) compounds.

  10. Host-guest complexes of 2-hydroxypropyl-β-cyclodextrin/β-cyclodextrin and nifedipine: 1H NMR, molecular modeling, and dissolution studies

    Science.gov (United States)

    de Araújo, Márcia Valéria Gaspar; Vieira, João Victor Francisco; da Silva, Caroline W. P.; Barison, Andersson; Andrade, George Ricardo Santana; da Costa, Nivan Bezerra; Barboza, Fernanda Malaquias; Nadal, Jessica Mendes; Novatski, Andressa; Farago, Paulo Vitor; Zawadzki, Sônia Faria

    2017-12-01

    Nifedipine (NIF) is a hydrophobic drug widely used for treating cardiovascular diseases. This calcium channel blocker can present a higher apparent solubility by its inclusion into different cyclodextrins (CDs) as host-guest complexes. This paper focused on the structural investigation and dissolution behavior of inclusion complexes prepared with 2-hydroxypropyl-β-cyclodextrin (HPβCD) or β-cyclodextrin (βCD) and NIF. Drug amorphization was observed for HPβCD/NIF and βCD/NIF inclusion complexes by X-ray diffractometry (XRD). The sharp endothermic peak of NIF was not observed for these both host-guest complexes by differential scanning calorimetry (DSC). These results of XRD and DSC provide evidences of complexation between drug and the investigated CDs. 1H and saturation transfer difference nuclear magnetic resonance studies revealed the enhancement in the signal at 2.27 ppm for HPβCD/NIF and βCD/NIF inclusion complexes that corresponded to the methyl groups of NIF from the non-aromatic ring. This result suggested that non-aromatic ring of NIF was inserted into HPβCD and βCD cavities. Considering the mathematical simulations, it was observed that the inclusion process can occur in the both NH-in or NH-out forms. However, since it was used aqueous medium, it is possible to indicate that the obtained host-guest complexes HPβCD/NIF and βCD/NIF are in NH-in form which corresponded to the previous results obtained by 1H NMR experiments. Dissolution assays demonstrated that NIF inclusion complexes improved the drug release nevertheless without changing its biexponential release behavior. These host-guest complexes can be further used as feasible NIF carriers in solid dosage forms.

  11. A supramolecular photosensitizer system based on the host-guest complexation between water-soluble pillar[6]arene and methylene blue for durable photodynamic therapy.

    Science.gov (United States)

    Yang, Kui; Wen, Jia; Chao, Shuang; Liu, Jing; Yang, Ke; Pei, Yuxin; Pei, Zhichao

    2018-06-05

    A supramolecular photosensitizer system WP6-MB was synthesized based on water-soluble pillar[6]arene and the photosensitizer methylene blue (MB) via host-guest interaction. MB can complex with WP6 directly with a high complex constant without further modification. In particular, WP6-MB can reduce the dark toxicity of MB remarkably. Furthermore, it can efficiently overcome photobleaching and extend the time for singlet oxygen production of MB upon light irradiation, which is significant for durable photodynamic therapy.

  12. New dendrimer - Peptide host - Guest complexes: Towards dendrimers as peptide carriers

    DEFF Research Database (Denmark)

    Boas, Ulrik; Sontjens, S.H.M.; Jensen, Knud Jørgen

    2002-01-01

    Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions...... between the dendrimer outer shell tertiary amines and the C-terminal carboxylic acid of the peptide, and also through host-urea to peptide-amide hydrogen bonding. The hydrogen-bonding nature of the peptide dendrimer interactions was further confirmed by using Fourier transform IR spectroscopy, for which...... the NH- and CO-stretch signals of the peptide amide moieties shift towards lower wave-numbers upon complexation with the dendrimer. Spatial analysis of the complexes with NOESY spectroscopy generally shows close proximity of the N-terminal Boc group of the peptide to the peripheral adamantyl groups...

  13. New dendrimer - peptide host - guest complexes : towards dendrimers as peptide carriers

    NARCIS (Netherlands)

    Boas, U.; Sontjens, S.H.M.; Jensen, K.J.; Christensen, J.B.; Meijer, E.W.

    2002-01-01

    Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions

  14. Host-guest chemistry of dendrimer-drug complexes. 2. Effects of molecular properties of guests and surface functionalities of dendrimers.

    Science.gov (United States)

    Hu, Jingjing; Cheng, Yiyun; Wu, Qinglin; Zhao, Libo; Xu, Tongwen

    2009-08-06

    The host-guest chemistry of dendrimer-drug complexes is investigated by NMR techniques, including (1)H NMR and 2D-NOESY studies. The effects of molecular properties of drug molecules (protonation ability and spatial steric hindrance of charged groups) and surface functionalities of dendrimers (positively charged amine groups and negatively charged carboxylate groups) on the host-guest interactions are discussed. Different interaction mechanisms between dendrimers and drug molecules are proposed on the basis of NMR results. Primary amine- and secondary amine-containing drugs preferentially bind to negatively charged dendrimers by strong electrostatic interactions, whereas tertiary amine and quaternary ammonium-containing drugs have weak binding ability with dendrimers due to relatively low protonation ability of the tertiary amine group and serious steric hindrance of the quaternary ammonium group. Positively charged drugs locate only on the surface of negatively charged dendrimers, whereas negatively charged drugs locate both on the surface and in the interior cavities of positively charged dendrimers. The host-guest chemistry of dendrimer-drug complexes is promising for the development of new drug delivery systems.

  15. Self-assembly behavior of a linear-star supramolecular amphiphile based on host-guest complexation.

    Science.gov (United States)

    Wang, Juan; Wang, Xing; Yang, Fei; Shen, Hong; You, Yezi; Wu, Decheng

    2014-11-04

    A star polymer, β-cyclodextrin-poly(l-lactide) (β-CD-PLLA), and a linear polymer, azobenzene-poly(ethylene glycol) (Azo-PEG), could self-assemble into a supramolecular amphiphilic copolymer (β-CD-PLLA@Azo-PEG) based on the host-guest interaction between β-CD and azobenzene moieties. This linear-star supramolecular amphiphilic copolymer further self-assembled into a variety of morphologies, including sphere-like micelle, carambola-like micelle, naan-like micelle, shuttle-like lamellae, tube-like fiber, and random curled-up lamellae, by tuning the length of hydrophilic or hydrophobic chains. The variation of morphology was closely related to the topological structure and block ratio of the supramolecular amphiphiles. These self-assembly structures could disassemble upon an ultraviolet (UV) light irradiation.

  16. Host-guest chemistry of dendrimer-drug complexes. 4. An in-depth look into the binding/encapsulation of guanosine monophosphate by dendrimers.

    Science.gov (United States)

    Hu, Jingjing; Fang, Min; Cheng, Yiyun; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen

    2010-06-03

    In the present study, we investigated the host-guest chemistry of dendrimer/guanosine monophosphate (GMP) and present an in-depth look into the binding/encapsulation of GMP by dendrimers using NMR studies. (1)H NMR spectra showed a significant downfield shift of methylene protons in the outmost layer of the G5 dendrimer, indicating the formation of ion pairs between cationic amine groups of dendrimer and anionic phosphate groups of GMP. Chemical shift titration results showed that the binding constant between G5 dendrimer and GMP is 17,400 M(-1) and each G5 dendrimer has 107 binding sites. The binding of GMP to dendrimers prevents its aggregation in aqueous solutions and thereby enhances its stability. Nuclear Overhauser effect measurements indicated that a GMP binding and encapsulation balance occurs on the surface and in the interior of dendrimer. The binding/encapsulation transitions can be easily tailored by altering the surface and interior charge densities of the dendrimer. All these findings provide a new insight into the host-guest chemistry of dendrimer/guest complexes and may play important roles in the study of dendrimer/DNA aggregates by a "bottom-up" strategy.

  17. Transfer and control of molecular chirality in the 1 : 2 host-guest supramolecular complex consisting of Mg(II)bisporphyrin and chiral diols: the effect of H-bonding on the rationalization of chirality.

    Science.gov (United States)

    Ikbal, Sk Asif; Brahma, Sanfaori; Rath, Sankar Prasad

    2014-11-21

    A clear rationalization of the origin of chirality transfer from an optically active diol guest to an achiral Mg(ii)bisporphyrin host in a series of 1 : 2 host-guest supramolecular complexes has been reported here that has so far remained the most outstanding issue for the chirogenic process.

  18. Can we beat the biotin-avidin pair?: cucurbit[7]uril-based ultrahigh affinity host-guest complexes and their applications.

    Science.gov (United States)

    Shetty, Dinesh; Khedkar, Jayshree K; Park, Kyeng Min; Kim, Kimoon

    2015-12-07

    The design of synthetic, monovalent host-guest molecular recognition pairs is still challenging and of particular interest to inquire into the limits of the affinity that can be achieved with designed systems. In this regard, cucurbit[7]uril (CB[7]), an important member of the host family cucurbit[n]uril (CB[n], n = 5-8, 10, 14), has attracted much attention because of its ability to form ultra-stable complexes with multiple guests. The strong hydrophobic effect between the host cavity and guests, ion-dipole and dipole-dipole interactions of guests with CB portals helps in cooperative and multiple noncovalent interactions that are essential for realizing such strong complexations. These highly selective, strong yet dynamic interactions can be exploited in many applications including affinity chromatography, biomolecule immobilization, protein isolation, biological catalysis, and sensor technologies. In this review, we summarize the progress in the development of high affinity guests for CB[7], factors affecting the stability of complexes, theoretical insights, and the utility of these high affinity pairs in different challenging applications.

  19. Host-guest chemistry of dendrimer-drug complexes. 6. Fully acetylated dendrimers as biocompatible drug vehicles using dexamethasone 21-phosphate as a model drug.

    Science.gov (United States)

    Yang, Kun; Weng, Liang; Cheng, Yiyun; Zhang, Hongfeng; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen

    2011-03-17

    Fully acetylated poly(amidoamine) (PAMAM) dendrimer was proposed as a biocompatible drug vehicle using dexamethasone 21-phosphate (Dp21) as a model drug. NMR techniques including (1)H NMR and 2D NOE NMR were used to characterize the host-guest chemistry of acetylated dendrimer/Dp21 and cationic dendrimer/Dp21 complexes. The pH-dependent micellization, complexation, and inclusion behaviors of Dp21 were observed in the presence of acetylated and cationic PAMAM dendrimers. Acetylated dendrimer only encapsulates Dp21 at acidic conditions, while cationic dendrimer can host Dp21 at both acidic and neutral conditions. The orientation of Dp21 molecules in the dendrimer cavities depends on the quaternization degree of tertiary amine groups of dendrimer and the protonation ratio of phosphate group of Dp21. A distinctive pH-dependent release behavior of Dp21 from the acetylated and nonacetylated dendritic matrix was observed: Dp21 exhibits a much slower release rate from acetylated dendrimer at lower pH conditions and a much faster release rate from nonacetylated dendrimer with decreasing pH values. Cytotoxicity studies further confirmed the biocompatibility of acetylated dendrimers, which are much safer in the delivery of therapeutics for the treatment of various diseases than nonacetylated dendrimers. The dendrimer-drug binding and release mechanisms provide a new insight for the design and optimization of biocompatible dendrimer-based drug delivery systems. © 2011 American Chemical Society

  20. Structural elucidation of dendritic host-guest complexes by X-ray crystallography and molecular dynamics simulations

    NARCIS (Netherlands)

    Chang, T.; Pieterse, K.; Broeren, M.A.C.; Kooijman, H.; Spek, A.L.; Hilbers, P.A.J.; Meijer, E.W.

    2007-01-01

    The multiple monovalent binding of adamantyl-urea poly(propyleneimine) dendrimers with carboxylic acid-urea guests was investigated using molecular dynamics simulations and X-ray crystallography to better understand the structure and behavior of the dynamic multivalent complex in solution. The

  1. Host-guest chemistry of dendrimer-drug complexes: 7. Formation of stable inclusions between acetylated dendrimers and drugs bearing multiple charges.

    Science.gov (United States)

    Fang, Min; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen; Cheng, Yiyun

    2012-03-15

    Drug molecules bearing multiple charges usually form precipitates with cationic dendrimers, which presents a challenge during the preparation of dendrimer inclusions for these drugs. In the present study, fully acetylated polyamidoamine (PAMAM) dendrimers were proposed as stable vehicles for drug molecules bearing two negative charges such as Congo red and indocyanine green. NMR techniques including (1)H NMR and (1)H-(1)H NOESY were used to characterize the host-guest chemistry of acetylated dendrimer and these guest molecules. The cationic PAMAM dendrimer was found to form a precipitate with Congo red and indocyanine green, but the acetylated one avoided the formation of cross-linking structures in aqueous solutions. NOESY studies revealed the encapsulation of Congo red and indocyanine green within the interior cavities of PAMAM dendrimers at mild acidic conditions and acetylated dendrimers show much stronger ability to encapsulate the guest molecules than cationic ones. Also, UV-vis-NIR studies suggest that acetylated dendrimers significantly improve the photostability of indocyanine green and prevent the formation of indocyanine green J-aggregates in aqueous solutions. The present study provides a new insight into dendrimer-based host-guest systems, especially for those guest molecules bearing multiple charges. © 2012 American Chemical Society

  2. Host-Guest Complexes of Cyclodextrins and Nanodiamonds as a Strong Non-Covalent Binding Motif for Self-Assembled Nanomaterials.

    Science.gov (United States)

    Schibilla, Frauke; Voskuhl, Jens; Fokina, Natalie A; Dahl, Jeremy E P; Schreiner, Peter R; Ravoo, Bart Jan

    2017-11-13

    We report the inclusion of carboxy- and amine-substituted molecular nanodiamonds (NDs) adamantane, diamantane, and triamantane by β-cyclodextrin and γ-cyclodextrin (β-CD and γ-CD), which have particularly well-suited hydrophobicity and symmetry for an optimal fit of the host and guest molecules. We studied the host-guest interactions in detail and generally observed 1:1 association of the NDs with the larger γ-CD cavity, but observed 1:2 association for the largest ND in the series (triamantane) with β-CD. We found higher binding affinities for carboxy-substituted NDs than for amine-substituted NDs. Additionally, cyclodextrin vesicles (CDVs) were decorated with d-mannose by using adamantane, diamantane, and triamantane as non-covalent anchors, and the resulting vesicles were compared with the lectin concanavalin A in agglutination experiments. Agglutination was directly correlated to the host-guest association: adamantane showed lower agglutination than di- or triamantane with β-CDV and almost no agglutination with γ-CDV, whereas high agglutination was observed for di- and triamantane with γ-CDV. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Host-Guest Inclusion Complexes between Amlodipine Enantiomers in the Biphasic Recognition Chiral Extraction System using Tartaric Acid and β-Cyclodextrin Derivatives as Positive Confirmation by using their Enantioselective Extraction.

    Science.gov (United States)

    Al Azzam, Khaldun M; Abdallah, Hassan H; Halim, Hairul N Abdul; Ahmad, Maizatul Akmam; Shaibah, Hassan

    2015-01-01

    The current work reports an extended theoretical study from our previous experimental work for the enantioselective extraction of amlodipine enantiomers in a biphasic recognition chiral extraction system (BRCES) consisting of hydrophobic D-diisopropyl tartrate dissolved in organic phase (n-decanol) and hydrophilic hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous phase (acetate buffer) which preferentially recognize the R-enantiomer and S-enantiomer, respectively. The calculations were simulated using a semi-empirical PM3 method as a part of the Gaussian09 software package and were used to optimize the structures of the hosts, guests, and host-guest complexes in the gas phase without any restrictions. It was found that HP-β-CD has the strongest recognition ability among the three β-CD derivatives studied, namely HP-β-CD, hydroxyethyl-β-cyclodextrin (HE-β-CD), and methylated-β-cyclodextrin (Me-β-CD), due to the large interaction energies (Ecomp = -14.3025 kcal/ mol), while D-diisopropyl tartrate has the strongest ability among the four tartaric acid derivatives studied namely; L-diisopropyl tartrate, D-diisopropyl tartrate, L-diethyl tartrate, and D-diethyl tartrate (Ecomp = -5.9964 kcal/ mol). The computational calculations for the enantioselective partitioning of amlodipine enantiomers rationalized the reasons for the different behaviors for this extraction. The present theoretical results may be informative to scientists who are devoting themselves to developing models for their experimental parts or for enhancing the hydrophobic drug solubility in drug delivery systems.

  4. Host-Guest Inclusion Complexes between Amlodipine Enantiomers in the Biphasic Recognition Chiral Extraction System using Tartaric Acid and β-Cyclodextrin Derivatives as Positive Confirmation by using their Enantioselective Extraction

    Science.gov (United States)

    Al Azzam, Khaldun M.; Abdallah, Hassan H.; Halim, Hairul N. Abdul; Ahmad, Maizatul Akmam; Shaibah, Hassan

    2015-01-01

    The current work reports an extended theoretical study from our previous experimental work for the enantioselective extraction of amlodipine enantiomers in a biphasic recognition chiral extraction system (BRCES) consisting of hydrophobic D-diisopropyl tartrate dissolved in organic phase (n-decanol) and hydrophilic hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous phase (acetate buffer) which preferentially recognize the R-enantiomer and S-enantiomer, respectively. The calculations were simulated using a semi-empirical PM3 method as a part of the Gaussian09 software package and were used to optimize the structures of the hosts, guests, and host-guest complexes in the gas phase without any restrictions. It was found that HP-β-CD has the strongest recognition ability among the three β-CD derivatives studied, namely HP-β-CD, hydroxyethyl-β-cyclodextrin (HE-β-CD), and methylated-β-cyclodextrin (Me-β-CD), due to the large interaction energies (Ecomp = −14.3025 kcal/ mol), while D-diisopropyl tartrate has the strongest ability among the four tartaric acid derivatives studied namely; L-diisopropyl tartrate, D-diisopropyl tartrate, L-diethyl tartrate, and D-diethyl tartrate (Ecomp = −5.9964 kcal/ mol). The computational calculations for the enantioselective partitioning of amlodipine enantiomers rationalized the reasons for the different behaviors for this extraction. The present theoretical results may be informative to scientists who are devoting themselves to developing models for their experimental parts or for enhancing the hydrophobic drug solubility in drug delivery systems. PMID:26839848

  5. Switchable host-guest systems on surfaces.

    Science.gov (United States)

    Yang, Ying-Wei; Sun, Yu-Long; Song, Nan

    2014-07-15

    CONSPECTUS: For device miniaturization, nanotechnology follows either the "top-down" approach scaling down existing larger-scale devices or the "bottom-up' approach assembling the smallest possible building blocks to functional nanoscale entities. For synthetic nanodevices, self-assembly on surfaces is a superb method to achieve useful functions and enable their interactions with the surrounding world. Consequently, adaptability and responsiveness to external stimuli are other prerequisites for their successful operation. Mechanically interlocked molecules such as rotaxanes and catenanes, and their precursors, that is, molecular switches and supramolecular switches including pseudorotaxanes, are molecular machines or prototypes of machines capable of mechanical motion induced by chemical signals, biological inputs, light or redox processes as the external stimuli. Switching of these functional host-guest systems on surfaces becomes a fundamental requirement for artificial molecular machines to work, mimicking the molecular machines in nature, such as proteins and their assemblies operating at dynamic interfaces such as the surfaces of cell membranes. Current research endeavors in material science and technology are focused on developing either a new class of materials or materials with novel/multiple functionalities by shifting host-guest chemistry from solution phase to surfaces. In this Account, we present our most recent attempts of building monolayers of rotaxanes/pseudorotaxanes on surfaces, providing stimuli-induced macroscopic effects and further understanding on the switchable host-guest systems at interfaces. Biocompatible versions of molecular machines based on synthetic macrocycles, such as cucurbiturils, pillararenes, calixarenes, and cyclodextrins, have been employed to form self-assembled monolayers of gates on the surfaces of mesoporous silica nanoparticles to regulate the controlled release of cargo/drug molecules under a range of external stimuli

  6. Enhanced detection of explosives by turn-on resonance Raman upon host-guest complexation in solution and the solid state

    DEFF Research Database (Denmark)

    Witlicki, Edward H.; Bähring, Steffen; Johnsen, Carsten

    2017-01-01

    complexation occur via a mechanism of resonance between the 785 nm laser line and the strongly absorbing charge-transfer chromophore arising from the complex between electron-donating TTF-C[4]P and electron-accepting nitroaromatic explosives. The addition of chloride forms the Cl-·TTF-C[4]P complex resetting......The recognition of nitroaromatic explosives by a tetrakis-tetrathiafulvalene-calix[4]pyrrole receptor (TTF-C[4]P) yields a "turn on" and fingerprinting response in the resonance Raman scattering observed in solution and the solid state. Intensity changes in nitro vibrations with analyte...

  7. Host-guest complex of N-(2-chloroethyl), N-nitroso, N‧, N‧ -dicyclohexylsulfamid with β-cyclodextrin: Fluorescence, QTAIM analysis and structure-chemical reactivity

    Science.gov (United States)

    Bensouilah, Nadjia; Fisli, Hassina; Bensouilah, Hamza; Zaater, Sihem; Abdaoui, Mohamed; Boutemeur-Kheddis, Baya

    2017-10-01

    In this work, the inclusion complex of DCY/CENS: N-(2-chloroethyl), N-nitroso, N‧, N‧-dicyclohexylsulfamid and β-cyclodextrin (β-CD) is investigated using the fluorescence spectroscopy, PM3, ONIOM2 and DFT methods. The experimental part reveals that DCY/CENS forms a 1:1 stoichiometric ratio inclusion complex with β-CD. The constant of stability is evaluated using the Benesi-Hildebrand equation. The results of the theoretical optimization showed that the lipophilic fraction of molecule (cyclohexyl group) is inside of β-CD. Accordingly, the Nitroso-Chloroethyl moiety is situated outside the cavity of the macromolecule host. The favorable structure of the optimized complex indicates the existence of weak intermolecular hydrogen bonds and the most important van der Waals (vdW) interactions which are studied on the basis of Natural Bonding Orbital (NBO) analysis. The NBO is employed to compute the electronic donor-acceptor exchanges between drug and β-CD. Furthermore, a detailed topological charge density analysis based on the quantum theory of atoms in molecules (QTAIM), has been accomplished on the most favorable complex using B3LYP/6-31G(d) method. The presence of stabilizing intermolecular hydrogen bonds and van der Waals interactions in the most favorable complex is predicted. Also, the energies of these interactions are estimated with Espinosa's formula. The findings of this investigation reveal that the correlation between the structural parameters and the electronic density is good. Finally, and based on DFT calculations, the reactivity of the interesting molecule in free state was studied and compared with that in the complexed state using chemical potential, global hardness, global softness, electronegativity, electrophilicity and local reactivity descriptors.

  8. Experimental and theoretical investigations on Pd(II) host-guest compound: Deciphering the structural and electronic features of a potential bioactive complex

    Science.gov (United States)

    Sreejith, S. S.; Mohan, Nithya; Prathapachandra Kurup, M. R.

    2017-10-01

    A Pd(II) complex from N,N‧-bis(2-hydroxy-3-ethoxybenzylidene)butane-1,4-diamine salen-type ligand has been synthesized and characterised using single crystal XRD analysis, elemental analysis, IR and UV-Vis spectroscopic methods. Thermal profile of the compound is investigated using TG-DTG-DSC method. The quantification of intermolecular interactions and surface morphology has been done using Hirshfeld surface study mapped using various functions like dnorm, shape index and curvedness. ESP analysis is done to visualize the electrophilic and nucleophilic regions in the complex. Geometry optimization of the structure is done using DFT at B3LYP/def2-TZVP level of theory. Frontier orbital analysis reveals the kinetical stability and chemical inertness of the complex. A detailed charge distribution analysis is done using different analytical methods like Mulliken, Löwdin, NPA and AIM methods. Further bond order analysis and topological analysis are also done. Finally the bioactivity of the titled complex is checked using molecular docking method on both DNA and protein.

  9. Biosynthesis of ketomycin. (II) biomimetic model for beta-lactamase catalysis: host-guest interactions in cyclodextrin-penicillin inclusion complex

    International Nuclear Information System (INIS)

    Mak, H.W.

    1986-01-01

    The antibiotic ketomycin is formed from shikimic acid via chorismic acid and prephenic acid. Phenylalanine and 2',5'-dihydrophenylalanine derived from shikimic acid are not intermediates in the biosynthesis. Degradation of ketomycin derived from [1,6- 14 C]shikimic acid showed that prephenic acid is converted into ketomycin with stereospecific discrimination between the two enantiotopic edges of the ring, the pro-S-R edge giving rise to the C-2', C-3' side of the cyclohexane ring of ketomycin. The resistance of pathogenic bacteria to the action of β-lactam antibiotics is mainly ascribed to their ability to produce β-lactamase to cleave the β-lactam ring. It is essential to understand the molecular nature of β-lactamase-penicillin recognition for designing and formulating more effective β-lactam antibiotics. A biomimetic study of β-lactamase is therefore initiated. To meet the requirements of hydrophobic and serine protease characteristics of β-lactamase, α-cyclodextrin is chosen as a biomimetic model for β-lactamase. The structural specificity and the chemical dynamics of α-cyclodextrin-phenoxymethyl penicillin inclusion complex in solid state and in solution have been determined by IR and NMR spectroscopy. The spectral results strongly indicate that the phenyl portion of the phenoxymethyl penicillin forms a stable inclusion complex with the hydrophobic cavity of α-cyclodextrin in solution as well as in the solid state. Kinetic studies followed by 1 HNMR and HPLC analyses under alkaline condition have shown that the α-cyclodextrin mimics the catalytic function of serine of β-lactamase in the stereospecific hydrolysis of the β-lactam ring of phenoxymethyl penicillin

  10. Controlling the Host-Guest Interaction Mode through a Redox Stimulus.

    Science.gov (United States)

    Szalóki, György; Croué, Vincent; Carré, Vincent; Aubriet, Frédéric; Alévêque, Olivier; Levillain, Eric; Allain, Magali; Aragó, Juan; Ortí, Enrique; Goeb, Sébastien; Sallé, Marc

    2017-12-18

    A proof-of-concept related to the redox-control of the binding/releasing process in a host-guest system is achieved by designing a neutral and robust Pt-based redox-active metallacage involving two extended-tetrathiafulvalene (exTTF) ligands. When neutral, the cage is able to bind a planar polyaromatic guest (coronene). Remarkably, the chemical or electrochemical oxidation of the host-guest complex leads to the reversible expulsion of the guest outside the cavity, which is assigned to a drastic change of the host-guest interaction mode, illustrating the key role of counteranions along the exchange process. The reversible process is supported by various experimental data ( 1 H NMR spectroscopy, ESI-FTICR, and spectroelectrochemistry) as well as by in-depth theoretical calculations performed at the density functional theory (DFT) level. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Supramolecular chemistry at interfaces: host-guest interactions for fabricating multifunctional biointerfaces.

    Science.gov (United States)

    Yang, Hui; Yuan, Bin; Zhang, Xi; Scherman, Oren A

    2014-07-15

    CONSPECTUS: Host-guest chemistry can greatly improve the selectivity of biomolecule-ligand binding on account of recognition-directed interactions. In addition, functional structures and the actuation of supramolecular assemblies in molecular systems can be controlled efficiently through various host-guest chemistry. Together, these highly selective, strong yet dynamic interactions can be exploited as an alternative methodology for applications in the field of programmable and controllable engineering of supramolecular soft materials through the reversible binding between complementary components. Many processes in living systems such as biotransformation, transportation of matter, and energy transduction begin with interfacial molecular recognition, which is greatly influenced by various external stimuli at biointerfaces. Detailed investigations about the molecular recognition at interfaces can result in a better understanding of life science, and further guide us in developing new biomaterials and medicines. In order to mimic complicated molecular-recognition systems observed in nature that adapt to changes in their environment, combining host-guest chemistry and surface science is critical for fabricating the next generation of multifunctional biointerfaces with efficient stimuli-responsiveness and good biocompatibility. In this Account, we will summarize some recent progress on multifunctional stimuli-responsive biointerfaces and biosurfaces fabricated by cyclodextrin- or cucurbituril-based host-guest chemistry and highlight their potential applications including drug delivery, bioelectrocatalysis, and reversible adsorption and resistance of peptides, proteins, and cells. In addition, these biointerfaces and biosurfaces demonstrate efficient response toward various external stimuli, such as UV light, pH, redox chemistry, and competitive guests. All of these external stimuli can aid in mimicking the biological stimuli evident in complex biological environments

  12. Engineering responsive polymer building blocks with host-guest molecular recognition for functional applications.

    Science.gov (United States)

    Hu, Jinming; Liu, Shiyong

    2014-07-15

    CONSPECTUS: All living organisms and soft matter are intrinsically responsive and adaptive to external stimuli. Inspired by this fact, tremendous effort aiming to emulate subtle responsive features exhibited by nature has spurred the invention of a diverse range of responsive polymeric materials. Conventional stimuli-responsive polymers are constructed via covalent bonds and can undergo reversible or irreversible changes in chemical structures, physicochemical properties, or both in response to a variety of external stimuli. They have been imparted with a variety of emerging applications including drug and gene delivery, optical sensing and imaging, diagnostics and therapies, smart coatings and textiles, and tissue engineering. On the other hand, in comparison with molecular chemistry held by covalent bonds, supramolecular chemistry built on weak and reversible noncovalent interactions has emerged as a powerful and versatile strategy for materials fabrication due to its facile accessibility, extraordinary reversibility and adaptivity, and potent applications in diverse fields. Typically involving more than one type of noncovalent interactions (e.g., hydrogen bonding, metal coordination, hydrophobic association, electrostatic interactions, van der Waals forces, and π-π stacking), host-guest recognition refers to the formation of supramolecular inclusion complexes between two or more entities connected together in a highly controlled and cooperative manner. The inherently reversible and adaptive nature of host-guest molecular recognition chemistry, stemming from multiple noncovalent interactions, has opened up a new platform to construct novel types of stimuli-responsive materials. The introduction of host-guest chemistry not only enriches the realm of responsive materials but also confers them with promising new applications. Most intriguingly, the integration of responsive polymer building blocks with host-guest recognition motifs will endow the former with

  13. Atomic force microscopy imaging of macromolecular complexes.

    Science.gov (United States)

    Santos, Sergio; Billingsley, Daniel; Thomson, Neil

    2013-01-01

    This chapter reviews amplitude modulation (AM) AFM in air and its applications to high-resolution imaging and interpretation of macromolecular complexes. We discuss single DNA molecular imaging and DNA-protein interactions, such as those with topoisomerases and RNA polymerase. We show how relative humidity can have a major influence on resolution and contrast and how it can also affect conformational switching of supercoiled DNA. Four regimes of AFM tip-sample interaction in air are defined and described, and relate to water perturbation and/or intermittent mechanical contact of the tip with either the molecular sample or the surface. Precise control and understanding of the AFM operational parameters is shown to allow the user to switch between these different regimes: an interpretation of the origins of topographical contrast is given for each regime. Perpetual water contact is shown to lead to a high-resolution mode of operation, which we term SASS (small amplitude small set-point) imaging, and which maximizes resolution while greatly decreasing tip and sample wear and any noise due to perturbation of the surface water. Thus, this chapter provides sufficient information to reliably control the AFM in the AM AFM mode of operation in order to image both heterogeneous samples and single macromolecules including complexes, with high resolution and with reproducibility. A brief introduction to AFM, its versatility and applications to biology is also given while providing references to key work and general reviews in the field.

  14. Complex Macromolecular Architectures by Living Cationic Polymerization

    KAUST Repository

    Alghamdi, Reem D.

    2015-05-01

    Poly (vinyl ether)-based graft polymers have been synthesized by the combination of living cationic polymerization of vinyl ethers with other living or controlled/ living polymerization techniques (anionic and ATRP). The process involves the synthesis of well-defined homopolymers (PnBVE) and co/terpolymers [PnBVE-b-PCEVE-b-PSiDEGVE (ABC type) and PSiDEGVE-b-PnBVE-b-PSiDEGVE (CAC type)] by sequential living cationic polymerization of n-butyl vinyl ether (nBVE), 2-chloroethyl vinyl ether (CEVE) and tert-butyldimethylsilyl ethylene glycol vinyl ether (SiDEGVE), using mono-functional {[n-butoxyethyl acetate (nBEA)], [1-(2-chloroethoxy) ethyl acetate (CEEA)], [1-(2-(2-(t-butyldimethylsilyloxy)ethoxy) ethoxy) ethyl acetate (SiDEGEA)]} or di-functional [1,4-cyclohexanedimethanol di(1-ethyl acetate) (cHMDEA), (VEMOA)] initiators. The living cationic polymerizations of those monomers were conducted in hexane at -20 0C using Et3Al2Cl3 (catalyst) in the presence of 1 M AcOEt base.[1] The PCEVE segments of the synthesized block terpolymers were then used to react with living macroanions (PS-DPE-Li; poly styrene diphenyl ethylene lithium) to afford graft polymers. The quantitative desilylation of PSiDEGVE segments by n-Bu4N+F- in THF at 0 °C led to graft co- and terpolymers in which the polyalcohol is the outer block. These co-/terpolymers were subsequently subjected to “grafting-from” reactions by atom transfer radical polymerization (ATRP) of styrene to afford more complex macromolecular architectures. The base assisted living cationic polymerization of vinyl ethers were also used to synthesize well-defined α-hydroxyl polyvinylether (PnBVE-OH). The resulting polymers were then modified into an ATRP macro-initiator for the synthesis of well-defined block copolymers (PnBVE-b-PS). Bifunctional PnBVE with terminal malonate groups was also synthesized and used as a precursor for more complex architectures such as H-shaped block copolymer by “grafting-from” or

  15. Separation of radionuclides using host-guest materials

    International Nuclear Information System (INIS)

    Drabova, V.

    2014-01-01

    This thesis is focused on the development of complex procedure with using commercially available sorbents to separate anthropogenic actinides 237 Np, 241 Am, 238 Pu and 239 , 240 Pu and their determination in the liquid radioactive wastes by using alpha spectrometry. Abilities of using commercially available sorbent AnaLig(R)Pu-02 gel from IBC Advanced Technologies, Inc. were tested, this product belongs to host-guest materials based on molecular recognition technology. This material is capable of selectively capturing actinides in oxidation state IV. To adjust the oxidation state of 238 Pu and 239 , 240 Pu was used NaNO 2 . Pu(IV) forms in the medium of nitric acid complexes, [Np(NO 3 ) 6 ] - , which are captured on the column. For the second monitored radionuclide, neptunium is typical valence V, Np(V) in the concentrated nitric acid produces strong complexes, [Np(NO 3 ) 6 ] - , which are capable of the sorption on the column of AnaLig(R)Pu-02 gel. The most common state of americium in aqueous solutions is III. Whereas in this oxidation state, americium do not form complexes in 8 mol·dm -3 nitric acid is the result of the flow-through. On the base of experimental obtained results, solution of 0.1 mol·dm -3 NH 4 I in 9 mol·dm -3 HCl was selected for elution of plutonium. Neptunium was eluted from the column using 9 mol·dm -3 of HCl with addition of 0.5 cm 3 TiCl 3 . Optimizing conditions for the separation procedure was performed by using model solution of radioactive waste which was prepared according to the chemical composition of radioactive concentrate from NPP Mochovce and NPP Bohunice. The effect of the concentration of Fe 3+ , the effect of the concentration of the HCl, the effect of the concentration of the solution of NH 4 I and the effect of the volume of this solution to the yields of 238 Pu were studied. And also was studied the effect of 9 mol·dm -3 of HCl and the effect of volume of 15 % TiCl 3 to the yields of 237 Np. Sorbent DGA(R) Resin from

  16. Driving Forces Controlling Host-Guest Recognition in Supercritical Carbon Dioxide Solvent.

    Science.gov (United States)

    Ingrosso, Francesca; Altarsha, Muhannad; Dumarçay, Florence; Kevern, Gwendal; Barth, Danielle; Marsura, Alain; Ruiz-López, Manuel F

    2016-02-24

    The formation of supramolecular host-guest complexes is a very useful and widely employed tool in chemistry. However, supramolecular chemistry in non-conventional solvents such as supercritical carbon dioxide (scCO2 ), one of the most promising sustainable solvents, is still in its infancy. In this work, we explored a successful route to the development of green processes in supercritical CO2 by combining a theoretical approach with experiments. We were able to synthesize and characterize an inclusion complex between a polar aromatic molecule (benzoic acid) and peracetylated-β-cyclodextrin, which is soluble in the supercritical medium. This finding opens the way to wide, environmental friendly, applications of scCO2 in many areas of chemistry, including supramolecular synthesis, reactivity and catalysis, micro and nano-particle formation, molecular recognition, as well as enhanced extraction processes with increased selectivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Deciphering the perturbation effect of urea on the supramolecular host-guest interaction of biologically active hydrophobic molecule inside the nanocavity of cyclodextrins

    Energy Technology Data Exchange (ETDEWEB)

    Maity, Banibrata; Chatterjee, Aninda; Ahmed, Sayeed Ashique; Seth, Debabrata, E-mail: debabrata@iitp.ac.in

    2017-03-15

    The present work articulates the supramolecular interaction and the formation of host-guest complex between the biologically active hydrophobic coumarin derivative and cyclodextrins by using several spectroscopic, calorimetric and microscopic techniques. All the studies clearly revealed that in presence of cyclodextrins (CDs), coumarin forms 1:1 stoichiometric complex. From all the study, we have found that with gradual increasing the cavity diameter of the hosts, the binding efficiency of the complexes gradually increases. The small population of the non emissive twisted intramolecular charge transfer (TICT) state of coumarin molecule turns into highly emissive in presence of γ-CD owing to its greater cavity diameter. The emissive TICT band is not found in β-CD complex due to its comparative small hydrophilic exterior and less polar environment. The present finding also interpret the perturbation effect of urea on host-guest complexes. In the presence of urea, the TICT emissive band of γ-CD is completely diminished. From, {sup 1}H NMR study it was observed that –NEt{sub 2} moiety of 7-DCCAE molecule is deeply buried inside the hydrophobic cavity of the CDs and forms host-guest complexes. Isothermal titration calorimetry measurement also indicates the formation of 1:1 host-guest complexes.

  18. Macromolecular complexes of lysozyme with kappa carrageenan

    NARCIS (Netherlands)

    Antonov, Y.A.; Zhuravleva, I.L.; Cardinaels, R.; Moldenaers, P.

    2018-01-01

    We present a structural study of the complexation and binding of lysozyme (Lys) with kappa carrageenan (kCG) by means of turbidity measurements, phase analysis, dynamic and electrophoretic light scattering, differential scanning microcalorimetry (DSMC), confocal laser scanning (CLSM) microscopy,

  19. Criticality and Connectivity in Macromolecular Charge Complexation

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Jian; de Pablo, Juan J.

    2016-11-04

    We examine the role of molecular connectivity and architecture on the complexation of ionic macromolecules (polyelectrolytes) of finite size. A unified framework is developed and applied to evaluate the electrostatic correlation free energy for point-like, rod-like, and coil-like molecules. That framework is generalized to molecules of variable fractal dimensions, including dendrimers. Analytical expressions for the free energy, correlation length, and osmotic pressure are derived, thereby enabling consideration of the effects of charge connectivity, fractal dimension, and backbone stiffness on the complexation behavior of a wide range of polyelectrolytes. Results are presented for regions in the immediate vicinity of the critical region and far from it. A transparent and explicit expression for the coexistence curve is derived in order to facilitate analysis of experimentally observed phase diagrams.

  20. Radiation damage to nucleoprotein complexes in macromolecular crystallography

    International Nuclear Information System (INIS)

    Bury, Charles; Garman, Elspeth F.; Ginn, Helen Mary; Ravelli, Raimond B. G.; Carmichael, Ian; Kneale, Geoff; McGeehan, John E.

    2015-01-01

    Quantitative X-ray induced radiation damage studies employing a model protein–DNA complex revealed a striking partition of damage sites. The DNA component was observed to be far more resistant to specific damage compared with the protein. Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. In contrast, despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. Here a model protein–DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07–44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N 1 —C and sugar-phosphate C—O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses

  1. Host-Guest Interaction between Corona[n]arene and Bisquaternary Ammonium Derivatives for Fabricating Supra-Amphiphile.

    Science.gov (United States)

    Zeng, Lingda; Guo, Qing-Hui; Feng, Yuanning; Xu, Jiang-Fei; Wei, Yuhan; Li, Zhibo; Wang, Mei-Xiang; Zhang, Xi

    2017-06-13

    The interactions between a host, water-soluble corona[n]arene (S6-CAP), and a series of guests, bisquaternary ammonium derivatives (CnDAs), in water, were investigated. The host and guest can form 1:1 host-guest complex. Their binding constants decrease as the alkyl length of CnDAs increases, which can be tunable ranging from 10 3 to 10 6 M -1 . The binding processes are mainly entropy-driven, while the enthalpy changes also play an important role in enhancing the host-guest interactions. In addition, a supra-amphiphile was fabricated with S6-CAP and a normal surfactant bearing bisquaternary ammonium (C4R). The S6-CAP·C4R complex forms micellar aggregates in water, and the system possesses better assembling activity and dilution stability than its building block C4R. This study enriches the families of supra-amphiphiles with a new architecture, and employing such a supra-amphiphile in biofunctional materials is highly anticipated.

  2. Study on luminescence characteristics of blue OLED with phosphor-doped host-guest structure

    Science.gov (United States)

    Wang, Zhen; Liu, Fei; Zheng, Xin; Chen, Ai; Xie, Jia-feng; Zhang, Wen-xia

    2018-05-01

    In this study, we design and fabricate phosphor-doped host-guest structure organic light-emitting diodes (OLEDs), where the blue-ray iridium complex electrophosphorescent material FIrpic acts as object material. Properties of the device can be accommodated by changing the host materials, dopant concentration and thickness of the light-emitting layer. The study shows that the host material N,N'-dicarbazolyl-3,5-benzene (mCP) has a higher triplet excited state energy level, which can effectively prevent FIrpic triplet excited state energy backtracking to host material, thus the luminous efficiency is improved. When mCP is selected as the host material, the thickness of the light-emitting layer is 30 nm and the dopant concentration is 8 wt%, the excitons can be effectively confined in the light-emitting region. As a result, the maximum current efficiency and the maximum brightness of the blue device can reach 15.5 cd/A and 7 196.3 cd/m2, respectively.

  3. Thermosensitive Triterpenoid-Appended Polymers with Broad Temperature Tunability Regulated by Host-Guest Chemistry.

    Science.gov (United States)

    Hao, Jie; Gao, Yuxia; Li, Ying; Yan, Qiang; Hu, Jun; Ju, Yong

    2017-09-05

    Thermoresponsive water-soluble polymers are of great importance since they typically show a lower critical solution temperature (LCST) in aqueous media. In this research, the LCST change in broad temperature ranges of copolymers composed of natural glycyrrhetinic acid (GA)-based methacrylate and N,N'-dimethylacrylamides (DMAs) was investigated as a function of the concentration and the content of GA pendants. By complexation of GA pendants with β-cyclodextrin (β-CD), a side-chain polypseudorotaxane was obtained, which exhibited a significant increase in the LCST of copolymers. Moreover, the precisely reversible control of the LCST behavior was realized through adding a competing guest molecule, sodium 1-admantylcarboxylate. This work illustrates a simple and effective approach to endow water-soluble polymers with broad temperature tunability and helps us further understand the effect of a biocompatible host-guest complementary β-CD/GA pair on the thermoresponsive process. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. ComplexViewer: visualization of curated macromolecular complexes.

    Science.gov (United States)

    Combe, Colin W; Sivade, Marine Dumousseau; Hermjakob, Henning; Heimbach, Joshua; Meldal, Birgit H M; Micklem, Gos; Orchard, Sandra; Rappsilber, Juri

    2017-11-15

    Proteins frequently function as parts of complexes, assemblages of multiple proteins and other biomolecules, yet network visualizations usually only show proteins as parts of binary interactions. ComplexViewer visualizes interactions with more than two participants and thereby avoids the need to first expand these into multiple binary interactions. Furthermore, if binding regions between molecules are known then these can be displayed in the context of the larger complex. freely available under Apache version 2 license; EMBL-EBI Complex Portal: http://www.ebi.ac.uk/complexportal; Source code: https://github.com/MICommunity/ComplexViewer; Package: https://www.npmjs.com/package/complexviewer; http://biojs.io/d/complexviewer. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js. colin.combe@ed.ac.uk or juri.rappsilber@ed.ac.uk. © The Author 2017. Published by Oxford University Press.

  5. The complex portal--an encyclopaedia of macromolecular complexes.

    Science.gov (United States)

    Meldal, Birgit H M; Forner-Martinez, Oscar; Costanzo, Maria C; Dana, Jose; Demeter, Janos; Dumousseau, Marine; Dwight, Selina S; Gaulton, Anna; Licata, Luana; Melidoni, Anna N; Ricard-Blum, Sylvie; Roechert, Bernd; Skyzypek, Marek S; Tiwari, Manu; Velankar, Sameer; Wong, Edith D; Hermjakob, Henning; Orchard, Sandra

    2015-01-01

    The IntAct molecular interaction database has created a new, free, open-source, manually curated resource, the Complex Portal (www.ebi.ac.uk/intact/complex), through which protein complexes from major model organisms are being collated and made available for search, viewing and download. It has been built in close collaboration with other bioinformatics services and populated with data from ChEMBL, MatrixDB, PDBe, Reactome and UniProtKB. Each entry contains information about the participating molecules (including small molecules and nucleic acids), their stoichiometry, topology and structural assembly. Complexes are annotated with details about their function, properties and complex-specific Gene Ontology (GO) terms. Consistent nomenclature is used throughout the resource with systematic names, recommended names and a list of synonyms all provided. The use of the Evidence Code Ontology allows us to indicate for which entries direct experimental evidence is available or if the complex has been inferred based on homology or orthology. The data are searchable using standard identifiers, such as UniProt, ChEBI and GO IDs, protein, gene and complex names or synonyms. This reference resource will be maintained and grow to encompass an increasing number of organisms. Input from groups and individuals with specific areas of expertise is welcome. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Field-induced detrapping in disordered organic semiconducting host-guest systems

    NARCIS (Netherlands)

    Cottaar, J.; Coehoorn, R.; Bobbert, P.A.

    2010-01-01

    In a disordered organic semiconducting host-guest material, containing a relatively small concentration of guest molecules acting as traps, the charge transport may be viewed as resulting from carriers that are detrapped from the guest to the host. Commonly used theories include only detrapping due

  7. Nanoparticles functionalized with supramolecular host-guest systems for nanomedicine and healthcare.

    Science.gov (United States)

    Wu, Zilong; Song, Nan; Menz, Ryan; Pingali, Bharadwaj; Yang, Ying-Wei; Zheng, Yuebing

    2015-05-01

    Synthetic macrocyclic host compounds can interact with suitable guest molecules via noncovalent interactions to form functional supramolecular systems. With the synergistic integration of the response of molecules and the unique properties at the nanoscale, nanoparticles functionalized with the host-guest supramolecular systems have shown great potentials for a broad range of applications in the fields of nanoscience and nanotechnology. In this review article, we focus on the applications of the nanoparticles functionalized with supramolecular host-guest systems in nanomedicine and healthcare, including therapeutic delivery, imaging, sensing and removal of harmful substances. A large number of examples are included to elucidate the working mechanisms, advantages, limitations and future developments of the nanoparticle-supramolecule systems in these applications.

  8. Toward Improved Force-Field Accuracy through Sensitivity Analysis of Host-Guest Binding Thermodynamics

    Science.gov (United States)

    Yin, Jian; Fenley, Andrew T.; Henriksen, Niel M.; Gilson, Michael K.

    2015-01-01

    Improving the capability of atomistic computer models to predict the thermodynamics of noncovalent binding is critical for successful structure-based drug design, and the accuracy of such calculations remains limited by non-optimal force field parameters. Ideally, one would incorporate protein-ligand affinity data into force field parametrization, but this would be inefficient and costly. We now demonstrate that sensitivity analysis can be used to efficiently tune Lennard-Jones parameters of aqueous host-guest systems for increasingly accurate calculations of binding enthalpy. These results highlight the promise of a comprehensive use of calorimetric host-guest binding data, along with existing validation data sets, to improve force field parameters for the simulation of noncovalent binding, with the ultimate goal of making protein-ligand modeling more accurate and hence speeding drug discovery. PMID:26181208

  9. Porphyrinic supramolecular daisy chains incorporating pillar[5]arene-viologen host-guest interactions

    KAUST Repository

    Fathalla, Maher; Strutt, Nathan; Srinivasan, Sampath; Katsiev, Khabiboulakh; Hartlieb, Karel J.; Bakr, Osman; Stoddart, J. Fraser

    2015-01-01

    A porphyrin functionalised with pillar[5]arene and a viologen at its 5- and 15-meso positions assembles in a head-to-tail manner, producing linear supramolecular daisy chains in dichloromethane. At high concentrations, it forms an organogel which has been investigated by electron microscopy and rheological measurements, paving the way for the preparation of other functional supramolecular assemblies which harness viologen"⊂" pillararene host-guest interactions.

  10. Porphyrinic supramolecular daisy chains incorporating pillar[5]arene-viologen host-guest interactions

    KAUST Repository

    Fathalla, Maher

    2015-05-18

    A porphyrin functionalised with pillar[5]arene and a viologen at its 5- and 15-meso positions assembles in a head-to-tail manner, producing linear supramolecular daisy chains in dichloromethane. At high concentrations, it forms an organogel which has been investigated by electron microscopy and rheological measurements, paving the way for the preparation of other functional supramolecular assemblies which harness viologen"⊂" pillararene host-guest interactions.

  11. Incommensurate host-guest structures in compressed elements: Hume—Rothery effects as origin

    International Nuclear Information System (INIS)

    Degtyareva, V F

    2015-01-01

    Discovery of the incommensurate structure in the element Ba under pressure 15 years ago was followed by findings of a series of similar structures in other compressed elements. Incommensurately modulated structures of the host-guest type consist of a tetragonal host structure and a guest structure. The guest structure forms chains of atoms embedded in the channels of host atoms so that the axial ratio of these subcells along the c axis is not rational. Two types of the host-guest structures have been found so far: with the host cells containing 8 atoms and 16 atoms; in these both types the guest cells contain 2 atoms. These crystal structures contain a non-integer number of atoms in their unit cell: tI11* in Bi, Sb, As, Ba, Sr, Sc and tI19* in Na, K, Rb. We consider here a close structural relationship of these host-guest structures with the binary alloy phase Au 3 Cd 5 -tI32. This phase is related to the family of the Hume-Rothery phases that is stabilized by the Fermi sphere-Brillouin zone interaction. From similar considerations for alkali and alkaline-earth elements a necessary condition for structural stability emerges in which the valence electrons band overlaps with the upper core electrons and the valence electron count increases under compression. (paper)

  12. Defined Host-Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer.

    Science.gov (United States)

    Ostadhossein, Fatemeh; Misra, Santosh K; Mukherjee, Prabuddha; Ostadhossein, Alireza; Daza, Enrique; Tiwari, Saumya; Mittal, Shachi; Gryka, Mark C; Bhargava, Rohit; Pan, Dipanjan

    2016-08-22

    Signal transducer and activator of transcription factor 3 (STAT-3) is known to be overexpressed in cancer stem cells. Poor solubility and variable drug absorption are linked to low bioavailability and decreased efficacy. Many of the drugs regulating STAT-3 expression lack aqueous solubility; hence hindering efficient bioavailability. A theranostics nanoplatform based on luminescent carbon particles decorated with cucurbit[6]uril is introduced for enhancing the solubility of niclosamide, a STAT-3 inhibitor. The host-guest chemistry between cucurbit[6]uril and niclosamide makes the delivery of the hydrophobic drug feasible while carbon nanoparticles enhance cellular internalization. Extensive physicochemical characterizations confirm successful synthesis. Subsequently, the host-guest chemistry of niclosamide and cucurbit[6]uril is studied experimentally and computationally. In vitro assessments in human breast cancer cells indicate approximately twofold enhancement in IC 50 of drug. Fourier transform infrared and fluorescence imaging demonstrate efficient cellular internalization. Furthermore, the catalytic biodegradation of the nanoplatforms occur upon exposure to human myeloperoxidase in short time. In vivo studies on athymic mice with MCF-7 xenograft indicate the size of tumor in the treatment group is half of the controls after 40 d. Immunohistochemistry corroborates the downregulation of STAT-3 phosphorylation. Overall, the host-guest chemistry on nanocarbon acts as a novel arsenal for STAT-3 inhibition. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Paramagnetic NMR investigation of dendrimer-based host-guest interactions.

    Directory of Open Access Journals (Sweden)

    Fei Wang

    Full Text Available In this study, the host-guest behavior of poly(amidoamine (PAMAM dendrimers bearing amine, hydroxyl, or carboxylate surface functionalities were investigated by paramagnetic NMR studies. 2,2,6,6-Tetramethylpiperidinyloxy (TEMPO derivatives were used as paramagnetic guest molecules. The results showed that TEMPO-COOH significantly broaden the ¹H NMR peaks of amine- and hydroxyl-terminated PAMAM dendrimers. In comparison, no paramagnetic relaxation enhancement (PRE was observed between TEMPO-NH₂, TEMPO-OH and the three types of PAMAM dendrimers. The PRE phenomenon observed is correlated with the encapsulation of TEMPO-COOH within dendrimer pockets. Protonation of the tertiary amine groups within PAMAM dendrimers plays an important role during this process. Interestingly, the absence of TEMPO-COOH encapsulation within carboxylate-terminated PAMAM dendrimer is observed due to the repulsion of TEMPO-COO- anion and anionic dendrimer surface. The combination of paramagnetic probes and ¹H NMR linewidth analysis can be used as a powerful tool in the analysis of dendrimer-based host-guest systems.

  14. Energy-cascade organic photovoltaic devices incorporating a host-guest architecture.

    Science.gov (United States)

    Menke, S Matthew; Holmes, Russell J

    2015-02-04

    In planar heterojunction organic photovoltaic devices (OPVs), broad spectral coverage can be realized by incorporating multiple molecular absorbers in an energy-cascade architecture. Here, this approach is combined with a host-guest donor layer architecture previously shown to optimize exciton transport for the fluorescent organic semiconductor boron subphthalocyanine chloride (SubPc) when diluted in an optically transparent host. In order to maximize the absorption efficiency, energy-cascade OPVs that utilize both photoactive host and guest donor materials are examined using the pairing of SubPc and boron subnaphthalocyanine chloride (SubNc), respectively. In a planar heterojunction architecture, excitons generated on the SubPc host rapidly energy transfer to the SubNc guest, where they may migrate toward the dissociating, donor-acceptor interface. Overall, the incorporation of a photoactive host leads to a 13% enhancement in the short-circuit current density and a 20% enhancement in the power conversion efficiency relative to an optimized host-guest OPV combining SubNc with a nonabsorbing host. This work underscores the potential for further design refinements in planar heterojunction OPVs and demonstrates progress toward the effective separation of functionality between constituent OPV materials.

  15. A host-guest-recognition-based electrochemical aptasensor for thrombin detection.

    Science.gov (United States)

    Fan, Hao; Li, Hui; Wang, Qingjiang; He, Pingang; Fang, Yuzhi

    2012-05-15

    A sensitive electrochemical aptasensor for thrombin detection is presented based on the host-guest recognition technique. In this sensing protocol, a 15 based thrombin aptamer (ab. TBA) was dually labeled with a thiol at its 3' end and a 4-((4-(dimethylamino)phenyl)azo) benzoic acid (dabcyl) at its 5' end, respectively, which was previously immobilized on one Au electrode surface by AuS bond and used as the thrombin probe during the protein sensing procedure. One special electrochemical marker was prepared by modifying CdS nanoparticle with β-cyclodextrins (ab. CdS-CDs), which employed as electrochemical signal provider and would conjunct with the thrombin probe modified electrode through the host-guest recognition of CDs to dabcyl. In the absence of thrombin, the probe adopted linear structure to conjunct with CdS-CDs. In present of thrombin, the TBA bond with thrombin and transformed into its special G-quarter structure, which forced CdS-CDs into the solution. Therefore, the target-TBA binding event can be sensitively transduced via detecting the electrochemical oxidation current signal of Cd of CdS nanoparticles in the solution. Using this method, as low as 4.6 pM thrombin had been detected. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Supra-dendron Gelator Based on Azobenzene-Cyclodextrin Host-Guest Interactions: Photoswitched Optical and Chiroptical Reversibility.

    Science.gov (United States)

    Xie, Fan; Ouyang, Guanghui; Qin, Long; Liu, Minghua

    2016-12-12

    A novel amphiphilic dendron (AZOC 8 GAc) with three l-glutamic acid units and an azobenzene moiety covalently linked by an alkyl spacer has been designed. The compound formed hydrogels with water at very low concentration and self-assembled into chiral-twist structures. The gel showed a reversible macroscopic volume phase transition in response to pH variations and photo-irradiation. During the photo-triggered changes, although the gel showed complete reversibility in its optical absorptions, only an incomplete chiroptical property change was achieved. On the other hand, the dendron could form a 1:1 inclusion complex through a host-guest interaction with α-cyclodextrin (α-CD), designated as supra-dendron gelator AZOC 8 GAc/α-CD. The supra-dendron showed similar gelation behavior to that of AZOC 8 GAc, but with enhanced photoisomerization-transition efficiency and chiroptical switching capacity, which was completely reversible in terms of both optical and chiroptical performances. The self-assembly of the supra-dendron is a hierarchical or multi-supramolecular self-assembling process. This work has clearly illustrated that the hierarchical and multi-supramolecular self-assembling system endows the supramolecular nanostructures or materials with superior reversible optical and chiroptical switching. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Vibrational spectroscopic and quantum theoretical study of host-guest interactions in clathrates: I. Hofmann type clathrates

    Directory of Open Access Journals (Sweden)

    VLADIMIR M. PETRUSEVSKI

    2000-06-01

    Full Text Available Hofmann type clatharates are host-guest compounds with the general formula M(NH32M'(CN4·2G, in which M(NH32M'(CN4 is the host lattice and G is benzene, the guest molecule. In previous studies, host-guest interactions have been investigated by analyzing the RT and LNT vibrational (infrared, far infrared and Raman spectra of these clathrates. All the observed changes in the vibrational spectra of these clathrates are referred to a host-guest interaction originating from weak hydrogen bonding between the ammonia hydrogen atoms from the host lattice and the p electron cloud of the guest (benzene molecules. In order to obtain an insight into the relative importance of the local crystalline field vs. the anharmonicity effects on the spectroscopic properties of the guest species upon enclathration, as well as to explain the observed band shifts and splittings, several quantum theoretical approaches are proposed.

  18. Rational Design of Multifunctional Gold Nanoparticles via Host-Guest Interaction for Cancer-Targeted Therapy.

    Science.gov (United States)

    Chen, Wei-Hai; Lei, Qi; Luo, Guo-Feng; Jia, Hui-Zhen; Hong, Sheng; Liu, Yu-Xin; Cheng, Yin-Jia; Zhang, Xian-Zheng

    2015-08-12

    A versatile gold nanoparticle-based multifunctional nanocomposite AuNP@CD-AD-DOX/RGD was constructed flexibly via host-guest interaction for targeted cancer chemotherapy. The pH-sensitive anticancer prodrug AD-Hyd-DOX and the cancer-targeted peptide AD-PEG8-GRGDS were modified on the surface of AuNP@CD simultaneously, which endowed the resultant nanocomposite with the capability to selectively eliminate cancer cells. In vitro studies indicated that the AuNP@CD-AD-DOX/RGD nanocomposite was preferentially uptaken by cancer cells via receptor-mediated endocytosis. Subsequently, anticancer drug DOX was released rapidly upon the intracellular trigger of the acid microenvirenment of endo/lysosomes, inducing apoptosis in cancer cells. As the ideal drug nanocarrier, the multifunctional gold nanoparticles with the active targeting and controllable intracellular release ability hold the great potential in cancer therapy.

  19. Using lanthanoid complexes to phase large macromolecular assemblies

    International Nuclear Information System (INIS)

    Talon, Romain; Kahn, Richard; Durá, M. Asunción; Maury, Olivier; Vellieux, Frédéric M. D.; Franzetti, Bruno; Girard, Eric

    2011-01-01

    A lanthanoid complex, [Eu(DPA) 3 ] 3− , was used to obtain experimental phases at 4.0 Å resolution of PhTET1-12s, a large self-compartmentalized homo-dodecameric protease complex of 444 kDa. Lanthanoid ions exhibit extremely large anomalous X-ray scattering at their L III absorption edge. They are thus well suited for anomalous diffraction experiments. A novel class of lanthanoid complexes has been developed that combines the physical properties of lanthanoid atoms with functional chemical groups that allow non-covalent binding to proteins. Two structures of large multimeric proteins have already been determined by using such complexes. Here the use of the luminescent europium tris-dipicolinate complex [Eu(DPA) 3 ] 3− to solve the low-resolution structure of a 444 kDa homododecameric aminopeptidase, called PhTET1-12s from the archaea Pyrococcus horikoshii, is reported. Surprisingly, considering the low resolution of the data, the experimental electron density map is very well defined. Experimental phases obtained by using the lanthanoid complex lead to maps displaying particular structural features usually observed in higher-resolution maps. Such complexes open a new way for solving the structure of large molecular assemblies, even with low-resolution data

  20. So how do you know you have a macromolecular complex?

    International Nuclear Information System (INIS)

    Dafforn, Timothy R.

    2007-01-01

    Structures of protein complexes offer some of the most interesting insights into biological processes. In this article, the methods required to show that the complex observed is the physiological one are investigated. Protein in crystal form is at an extremely high concentration and yet retains the complex secondary structure that defines an active protein. The protein crystal itself is made up of a repeating lattice of protein–protein and protein–solvent interactions. The problem that confronts any crystallographer is to identify those interactions that represent physiological interactions and those that do not. This review explores the tools that are available to provide such information using the original crystal liquor as a sample. The review is aimed at postgraduate and postdoctoral researchers who may well be coming up against this problem for the first time. Techniques are discussed that will provide information on the stoichiometry of complexes as well as low-resolution information on complex structure. Together, these data will help to identify the physiological complex

  1. Coevolutionary constraints in the sequence-space of macromolecular complexes reflect their self-assembly pathways.

    Science.gov (United States)

    Mallik, Saurav; Kundu, Sudip

    2017-07-01

    Is the order in which biomolecular subunits self-assemble into functional macromolecular complexes imprinted in their sequence-space? Here, we demonstrate that the temporal order of macromolecular complex self-assembly can be efficiently captured using the landscape of residue-level coevolutionary constraints. This predictive power of coevolutionary constraints is irrespective of the structural, functional, and phylogenetic classification of the complex and of the stoichiometry and quaternary arrangement of the constituent monomers. Combining this result with a number of structural attributes estimated from the crystal structure data, we find indications that stronger coevolutionary constraints at interfaces formed early in the assembly hierarchy probably promotes coordinated fixation of mutations that leads to high-affinity binding with higher surface area, increased surface complementarity and elevated number of molecular contacts, compared to those that form late in the assembly. Proteins 2017; 85:1183-1189. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Extraction of cobalt ion from textile using a complexing macromolecular surfactant in supercritical carbon dioxide

    International Nuclear Information System (INIS)

    Chirat, Mathieu; Ribaut, Tiphaine; Clerc, Sebastien; Lacroix-Desmazes, Patrick; Charton, Frederic; Fournel, Bruno

    2013-01-01

    Cobalt ion under the form of cobalt nitrate is removed from a textile lab coat using supercritical carbon dioxide extraction. The process involves a macromolecular additive of well-defined architecture, acting both as a surfactant and a complexing agent. The extraction efficiency of cobalt reaches 66% when using a poly(1,1,2,2-tetrahydroperfluoro-decyl-acrylate-co-vinyl-benzylphosphonic diacid) gradient copolymer in the presence of water at 160 bar and 40 C. The synergy of the two additives, namely the copolymer and water which are useless if used separately, is pointed out. The potential of the supercritical carbon dioxide process using complexing macromolecular surfactant lies in the ability to modulate the complexing unit as a function of the metal as well as the architecture of the surface-active agent for applications ranging for instance from nuclear decontamination to the recovery of strategic metals. (authors)

  3. Host-guest interaction of styrene and ethylbenzene in MIL-53 studied by solid-state NMR.

    Science.gov (United States)

    Li, Shenhui; Li, Jing; Tang, Jing; Deng, Feng

    Solid-state NMR was utilized to explore the host-guest interaction between adsorbate and adsorbent at atomic level to understand the separation mechanism of styrene (St) and ethylbenzene (EB) in MIL-53(Al). 13 C- 27 Al double-resonance NMR experiments revealed that the host-guest interaction between St and MIL-53 was much stronger than that of EB adsorption. In addition, 13 C DIPSHIFT experiments suggested that the adsorbed St was less mobile than EB confined inside the MIL-53 pore. Furthermore, the host-guest interaction model between St, EB and MIL-53 was established on the basis of the spatial proximities information extracted from 2D 1 H- 1 H homo-nuclear correlation NMR experiments. According to the experimental observation from solid-state NMR, it was found that the presence of π-π interaction between St and MIL-53 resulted in the stronger host-guest interaction and less mobility of St. This work provides direct experimental evidence for understanding the separation mechanism of St and EB using MIL-53 as an adsorbent. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. The dominating macromolecular complex of human gallbladder bile

    NARCIS (Netherlands)

    Verschure, J.C.M.; Mijnlieff, P.F.

    The solutes of human gall bladder bile appear to exist mainly in the form of a complex macromolecule, formed around a nucleus of lipoprotein. The existence of this macromolecule was demonstrated by paper electrophoresis1, free electrophoresis and ultracentrifuge experiments. The molecular weight of

  5. Pressure-induced chemistry in a nitrogen-hydrogen host-guest structure

    Science.gov (United States)

    Spaulding, Dylan K.; Weck, Gunnar; Loubeyre, Paul; Datchi, Fréderic; Dumas, Paul; Hanfland, Michael

    2014-12-01

    New topochemistry in simple molecular systems can be explored at high pressure. Here we examine the binary nitrogen/hydrogen system using Raman spectroscopy, synchrotron X-ray diffraction, synchrotron infrared microspectroscopy and visual observation. We find a eutectic-type binary phase diagram with two stable high-pressure van der Waals compounds, which we identify as (N2)6(H2)7 and N2(H2)2. The former represents a new type of van der Waals host-guest compound in which hydrogen molecules are contained within channels in a nitrogen lattice. This compound shows evidence for a gradual, pressure-induced change in bonding from van der Waals to ionic interactions near 50 GPa, forming an amorphous dinitrogen network containing ionized ammonia in a room-temperature analogue of the Haber-Bosch process. Hydrazine is recovered on decompression. The nitrogen-hydrogen system demonstrates the potential for new pressure-driven chemistry in high-pressure structures and the promise of tailoring molecular interactions for materials synthesis.

  6. Selective Organic and Organometallic Reactions in Water-Soluble Host-Guest Supramolecular Systems

    Energy Technology Data Exchange (ETDEWEB)

    Pluth, Michael D.; Raymond, Kenneth N.; Bergman, Robert G.

    2008-02-16

    Inspired by the efficiency and selectivity of enzymes, synthetic chemists have designed and prepared a wide range of host molecules that can bind smaller molecules with their cavities; this area has become known as 'supramolecular' or 'host-guest' chemistry. Pioneered by Lehn, Cram, Pedersen, and Breslow, and followed up by a large number of more recent investigators, it has been found that the chemical environment in each assembly - defined by the size, shape, charge, and functional group availability - greatly influences the guest-binding characteristics of these compounds. In contrast to the large number of binding studies that have been carried out in this area, the exploration of chemistry - especially catalytic chemistry - that can take place inside supramolecular host cavities is still in its infancy. For example, until the work described here was carried out, very few examples of organometallic reactivity inside supramolecular hosts were known, especially in water solution. For that reason, our group and the group directed by Kenneth Raymond decided to take advantage of our complementary expertise and attempt to carry out metal-mediated C-H bond activation reactions in water-soluble supramolecular systems. This article begins by providing background from the Raymond group in supramolecular coordination chemistry and the Bergman group in C-H bond activation. It goes on to report the results of our combined efforts in supramolecular C-H activation reactions, followed by extensions of this work into a wider range of intracavity transformations.

  7. Mechanical measurement of hydrogen bonded host-guest systems under non-equilibrium, near-physiological conditions.

    Science.gov (United States)

    Naranjo, Teresa; Cerrón, Fernando; Nieto-Ortega, Belén; Latorre, Alfonso; Somoza, Álvaro; Ibarra, Borja; Pérez, Emilio M

    2017-09-01

    Decades after the birth of supramolecular chemistry, there are many techniques to measure noncovalent interactions, such as hydrogen bonding, under equilibrium conditions. As ensembles of molecules rapidly lose coherence, we cannot extrapolate bulk data to single-molecule events under non-equilibrium conditions, more relevant to the dynamics of biological systems. We present a new method that exploits the high force resolution of optical tweezers to measure at the single molecule level the mechanical strength of a hydrogen bonded host-guest pair out of equilibrium and under near-physiological conditions. We utilize a DNA reporter to unambiguously isolate single binding events. The Hamilton receptor-cyanuric acid host-guest system is used as a test bed. The force required to dissociate the host-guest system is ∼17 pN and increases with the pulling rate as expected for a system under non-equilibrium conditions. Blocking one of the hydrogen bonding sites results in a significant decrease of the force-to-break by 1-2 pN, pointing out the ability of the method to resolve subtle changes in the mechanical strength of the binding due to the individual H-bonding components. We believe the method will prove to be a versatile tool to address important questions in supramolecular chemistry.

  8. The synthesis and host-guest applications of synthetic receptor molecules

    Science.gov (United States)

    Osner, Zachary R.

    2011-12-01

    Host-guest chemistry involves the complimentary binding between two molecules. Host molecules have been synthesized to bind negative, positive, and neutral molecules such as proteins and enzymes, and have been used as optical sensors, electrochemical sensors, supramolecular catalysts, and in the pharmaceutical industry as anti-cancer agents.1 The field of nanoscience has exploited guest-host interactions to create optical sensors with colloidal gold and Dip-Pen nanolithography technologies. Gold nanoparticles, have been functionalized with DNA, and have been developed as a selective colorimetric detection system, that upon binding turns the solution from a red to blue in color.2 Cyclotriveratrylene (CTV) 1 is a common supramolecular scaffold that has been previously employed in guest-host chemistry, and the construction of CTV involves the cyclic trimerization of veratryl alcohol via the veratryl cation.3 Due to the rigid bowl shaped structure of CTV, CTV has been shown to act as a host molecule for fullerene-C60.4 Lectin binding receptor proteins are a specific class of proteins found in bacteria, viruses, plants, and animals that can bind to complimentary carbohydrates. It is these lectins that are believed to be responsible for cell-cell interactions and the formation of biofilms in pathenogenic bacteria.5 P. aeruginosa is a pathenogenic bacterium, shown to have a high resistance to many antibiotics, which can form biofilms in human lung tissue, causing respiratory tract infections in patients with compromised immune systems. 5 I will exploit guest-host interactions to create synthetic supramolecular and carbohydrate receptor molecules to that will be of use as biological sensing devices via self-assembled monolayers on solid surfaces and nanoparticle technologies. *Please refer to dissertation for references/footnotes.

  9. Polydisulfide Manganese(II) Complexes as Non-Gadolinium Biodegradable Macromolecular MRI Contrast Agents

    Science.gov (United States)

    Ye, Zhen; Jeong, Eun-Kee; Wu, Xueming; Tan, Mingqian; Yin, Shouyu; Lu, Zheng-Rong

    2011-01-01

    Purpose To develop safe and effective manganese(II) based biodegradable macromolecular MRI contrast agents. Materials and Methods In this study, we synthesized and characterized two polydisulfide manganese(II) complexes, Mn-DTPA cystamine copolymers and Mn-EDTA cystamine copolymers, as new biodegradable macromolecular MRI contrast agents. The contrast enhancement of the two manganese based contrast agents were evaluated in mice bearing MDA-MB-231 human breast carcinoma xenografts, in comparison with MnCl2. Results The T1 and T2 relaxivities were 4.74 and 10.38 mM−1s−1 per manganese at 3T for Mn-DTPA cystamine copolymers (Mn=30.50 kDa) and 6.41 and 9.72 mM−1s−1 for Mn-EDTA cystamine copolymers (Mn= 61.80 kDa). Both polydisulfide Mn(II) complexes showed significant liver, myocardium and tumor enhancement. Conclusion The manganese based polydisulfide contrast agents have a potential to be developed as alternative non-gadolinium contrast agents for MR cancer and myocardium imaging. PMID:22031457

  10. Proteome-wide dataset supporting the study of ancient metazoan macromolecular complexes

    Directory of Open Access Journals (Sweden)

    Sadhna Phanse

    2016-03-01

    Full Text Available Our analysis examines the conservation of multiprotein complexes among metazoa through use of high resolution biochemical fractionation and precision mass spectrometry applied to soluble cell extracts from 5 representative model organisms Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Strongylocentrotus purpuratus, and Homo sapiens. The interaction network obtained from the data was validated globally in 4 distant species (Xenopus laevis, Nematostella vectensis, Dictyostelium discoideum, Saccharomyces cerevisiae and locally by targeted affinity-purification experiments. Here we provide details of our massive set of supporting biochemical fractionation data available via ProteomeXchange (http://www.ebi.ac.uk/pride/archive/projects/PXD002319-http://www.ebi.ac.uk/pride/archive/projects/PXD002328, PPIs via BioGRID (185267; and interaction network projections via (http://metazoa.med.utoronto.ca made fully accessible to allow further exploration. The datasets here are related to the research article on metazoan macromolecular complexes in Nature [1]. Keywords: Proteomics, Metazoa, Protein complexes, Biochemical, Fractionation

  11. Theoretical exploration of the nanoscale host-guest interactions between [n]cycloparaphenylenes (n = 10, 8 and 9) and fullerene C₆₀: from single- to three-potential well.

    Science.gov (United States)

    Yuan, Kun; Zhou, Cai-Hua; Zhu, Yuan-Cheng; Zhao, Xiang

    2015-07-28

    The nanoscale host-guest interactions between [n]cycloparaphenylene ([n]CPP; n = 10, 8 and 9) nano-ring and fullerene C60 were explored theoretically. It is found that relatively small variations in the sizes of the [n]CPP host lead to very significant changes in encapsulation property toward the fullerene C60 guest. Expectedly, one stable inclusion-configuration of [10]CPP⊃C60 and one floating-configuration of [8]CPP⊃C60 are located on the potential surfaces of the two complexes, respectively. Unexpectedly, besides a floating-configuration (F-[9]CPP⊃C60), another stable inclusion-configuration (I-[9]CPP⊃C60) is also located on the potential surface of [9]CPP⊃C60 host-guest complex. Interaction energies and natural steric analysis show that these complexes are stabilized by balancing concave-convex π-π attractive and steric repulsive host-guest interactions. In contrast, the steric repulsive energy (Es) between host and guest of I-[9]CPP⊃C60 is as high as 233.12 kJ mol(-1), which is much larger than those in other complexes. The movements of C60 guest through the cavities of [n]CPP host (n = 10, 8 and 9) are simulated by calculating the energy profile, and the results interestingly reveal that the encapsulation of C60 by [10]CPP is in the manner of a single-potential well, by [8]CPP in the manner of a double-potential well, and by [9]CPP in the special manner of a three-potential well. We predict that the movement of C60 guest through the cavity of [9]CPP host should be experimentally observable owing to the relatively low energy barrier (<50 kJ mol(-1), M06-2X/6-31G(d)). Charge population analysis shows that an obvious charge transfer between host and guest takes place during the formation of I-[9]CPP⊃C60, which is different from those during the formation of [8]CPP⊃C60, [10]CPP⊃C60 and F-[9]CPP⊃C60. Additionally, the host-guest interaction regions were detected and visualized in real space based on the electron density and reduced density

  12. C1 Polymerization: a unique tool towards polyethylene-based complex macromolecular architectures

    KAUST Repository

    Wang, De

    2017-05-09

    The recent developments in organoborane initiated C1 polymerization (chain grows by one atom at a time) of ylides opens unique horizons towards well-defined/perfectly linear polymethylenes (equivalent to polyethylenes, PE) and PE-based complex macromolecular architectures. The general mechanism of C1 polymerization (polyhomologation) involves the formation of a Lewis complex between a methylide (monomer) and a borane (initiator), followed by migration/insertion of a methylene into the initiator and after oxidation/hydrolysis to afford OH-terminated polyethylenes. This review summarizes efforts towards conventional and newly discovered borane-initiators and ylides (monomers), as well as a combination of polyhomologation with other polymerization methods. Initial efforts dealing with C3 polymerization and the synthesis of the first C1/C3 copolymers are also given. Finally, some thoughts for the future of these polymerizations are presented.

  13. C1 Polymerization: a unique tool towards polyethylene-based complex macromolecular architectures

    KAUST Repository

    Wang, De; Zhang, Zhen; Hadjichristidis, Nikolaos

    2017-01-01

    The recent developments in organoborane initiated C1 polymerization (chain grows by one atom at a time) of ylides opens unique horizons towards well-defined/perfectly linear polymethylenes (equivalent to polyethylenes, PE) and PE-based complex macromolecular architectures. The general mechanism of C1 polymerization (polyhomologation) involves the formation of a Lewis complex between a methylide (monomer) and a borane (initiator), followed by migration/insertion of a methylene into the initiator and after oxidation/hydrolysis to afford OH-terminated polyethylenes. This review summarizes efforts towards conventional and newly discovered borane-initiators and ylides (monomers), as well as a combination of polyhomologation with other polymerization methods. Initial efforts dealing with C3 polymerization and the synthesis of the first C1/C3 copolymers are also given. Finally, some thoughts for the future of these polymerizations are presented.

  14. Host-Guest Recognition-Assisted Electrochemical Release: Its Reusable Sensing Application Based on DNA Cross Configuration-Fueled Target Cycling and Strand Displacement Reaction Amplification.

    Science.gov (United States)

    Chang, Yuanyuan; Zhuo, Ying; Chai, Yaqin; Yuan, Ruo

    2017-08-15

    In this work, an elegantly designed host-guest recognition-assisted electrochemical release was established and applied in a reusable electrochemical biosensor for the detection of microRNA-182-5p (miRNA-182-5p), a prostate cancer biomarker in prostate cancer, based on the DNA cross configuration-fueled target cycling and strand displacement reaction (SDR) amplification. With such a design, the single target miRNA input could be converted to large numbers of single-stranded DNA (S1-Trp and S2-Trp) output, which could be trapped by cucurbit[8]uril methyl viologen (CB-8-MV 2+ ) based on the host-guest recognition, significantly enhancing the sensitivity for miRNA detection. Moreover, the nucleic acids products obtained from the process of cycling amplification could be utilized sufficiently, avoiding the waste and saving the experiment cost. Impressively, by resetting a settled voltage, the proposed biosensor could release S1-Trp and S2-Trp from the electrode surface, attributing that the guest ion methyl viologen (MV 2+ ) was reduced to MV +· under this settled voltage and formed a more-stable CB-8-MV +· -MV +· complex. Once O 2 was introduced in this system, MV +· could be oxidized to MV 2+ , generating the complex of CB-8-MV 2+ for capturing S1-Trp and S2-Trp again in only 5 min. As a result, the simple and fast regeneration of biosensor for target detection was realized on the base of electrochemical redox-driven assembly and release, overcoming the challenges of time-consuming, burdensome operations and expensive experimental cost in traditional reusable biosensors and updating the construction method for a reusable bisensor. Furthermore, the biosensor could be reused for more than 10 times with a regeneration rate of 93.20%-102.24%. After all, the conception of this work provides a novel thought for the construction of effective reusable biosensor to detect miRNA and other biomarkers and has great potential application in the area requiring the release of

  15. Site-selective electroless nickel plating on patterned thin films of macromolecular metal complexes.

    Science.gov (United States)

    Kimura, Mutsumi; Yamagiwa, Hiroki; Asakawa, Daisuke; Noguchi, Makoto; Kurashina, Tadashi; Fukawa, Tadashi; Shirai, Hirofusa

    2010-12-01

    We demonstrate a simple route to depositing nickel layer patterns using photocross-linked polymer thin films containing palladium catalysts, which can be used as adhesive interlayers for fabrication of nickel patterns on glass and plastic substrates. Electroless nickel patterns can be obtained in three steps: (i) the pattern formation of partially quaterized poly(vinyl pyridine) by UV irradiation, (ii) the formation of macromolecular metal complex with palladium, and (iii) the nickel metallization using electroless plating bath. Metallization is site-selective and allows for a high resolution. And the resulting nickel layered structure shows good adhesion with glass and plastic substrates. The direct patterning of metallic layers onto insulating substrates indicates a great potential for fabricating micro/nano devices.

  16. Vibrational spectroscopic and gravimetric study of some Hofmann-CBA-Type Host and host-guest compounds

    International Nuclear Information System (INIS)

    Aytekin, M.A.

    2005-01-01

    In this study, similar to Hofmann type M(C 4 H 7 NH 2 ) 2 Ni(CN) 4 (M=Ni or Co) host and M(C 4 H 7 NH 2 ) 2 Ni(CN) 4 .nG (M=Ni or Co; G=benzene, 1,2-, 1,3-dichlorobenzene; n=the number of guest) hostguest compounds were obtained chemically. The infrared spectra of these compounds were recorded with FT-IR spectrometer in the spectroscopic region of 4000cm-1-400cm-1. From these spectra the vibrational wave numbers of ligand molecule, Ni(CN) 4 2 - ion and guest molecules were determined. The absorption and the liberation processes of the guest molecules in the host compounds were examined at room temperature by gravimetric method. Otherwise, it was seen that the molecular structure was supported by making instrumental analysis of host and some host-guest compounds. By analysing the structures of host and host-guest compounds were found to be similar to those of Hofmann type compounds, ligand molecule cyclobutylamine were coordinated to M metal atom from cyclobutylamine's nitrogen atom, the guest molecules were imprisoned in the structural cavities between the sheets

  17. Supramolecular Host-Guest System as Ratiometric Fe3+ Ion Sensor Based on Water-Soluble Pillar[5]arene.

    Science.gov (United States)

    Yao, Qianfang; Lü, Baozhong; Ji, Chendong; Cai, Yang; Yin, Meizhen

    2017-10-18

    Developing a specific, ratiometric, and reversible detection method for metal ions is significant to guard against the threat of metal-caused environmental pollution and organisms poisoning. Here a supramolecular host-guest system (WP5⊃G) based on water-soluble pillar[5]arene (WP5) and water-soluble quaternized perylene diimide derivative (G) was constructed. Morphological transformation was achieved during the process of adding WP5 into G aqueous solution, and a fluorescence "turn-off" phenomenon was observed which was caused by supramolecular photoinduced electron transfer (PET). Meanwhile, hydrophobic effect and electrostatic interaction played important roles in this supramolecular process, which was confirmed by isothermal titration calorimeter (ITC) and ζ potential experiments. Furthermore, the supramolecular host-guest system could be a "turn-on" fluorescent probe for Fe 3+ ion detection through the process of interdicting supramolecular PET. Moreover, the Fe 3+ ion detection showed specific, ratiometric, and reversible performances with a detection limit of 2.13 × 10 -7 M, which might have great potentials in biological and environmental monitoring.

  18. Smart protein biogate as a mediator to regulate competitive host-guest interaction for sensitive ratiometric electrochemical assay of prion

    Science.gov (United States)

    Yu, Peng; Zhang, Xiaohua; Zhou, Jiawan; Xiong, Erhu; Li, Xiaoyu; Chen, Jinhua

    2015-11-01

    A novel competitive host-guest strategy regulated by protein biogate was developed for sensitive and selective analysis of prion protein. The methylene blue (MB)-tagged prion aptamer (MB-Apt) was introduced to the multiwalled carbon nanotubes-β-cyclodextrins (MWCNTs-β-CD) composites-modified glassy carbon (GC) electrode through the host-guest interaction between β-CD and MB. In the absence of prion, MB-Apt could be displaced by ferrocenecarboxylic acid (FCA) due to its stronger binding affinity to β-CD, resulting in a large oxidation peak of FCA. However, in the presence of prion, the specific prion-aptamer interaction drove the formation of protein biogate to seal the cavity of β-CD, which hindered the guest displacement of MB by FCA and resulted in the oxidation peak current of MB (IMB) increased and that of FCA (IFCA) decreased. The developed aptasensor showed good response towards the target (prion protein) with a low detection limit of 160 fM. By changing the specific aptamers, this strategy could be easily extended to detect other proteins, showing promising potential for extensive applications in bioanalysis.

  19. A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging.

    Science.gov (United States)

    Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

    2016-04-01

    The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Methyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex

    Science.gov (United States)

    Piras, Anna Maria; Fabiano, Angela; Chiellini, Federica; Zambito, Ylenia

    2018-01-01

    Purpose The present study aimed to compare a novel cyclodextrin–polymer–drug complex in solution with a dispersed supramolecular nanosize system, made of the same complex, for ability to carry dexamethasone (DEX) across excised rat intestine. Results Methyl-β-cyclodextrin-quaternary ammonium chitosan conjugate (QA-Ch-MCD) was obtained by covalent grafting through a 10-atom spacer. The conjugate was characterized by 1H-NMR, resulting in 24.4% w/w of MCD content. Phase solubility profile analysis of the QA-Ch-MCD/DEX complex yielded an association constant of 14037 M−1, vs 4428 M−1 for the plain MCD/DEX complex. Nanoparticle (NP) dispersions resulted from ionotropic gelation of the QA-Ch-MCD/DEX complex by sodium tripolyphosphate, leading to 9.9%±1.4% drug loading efficiency. The mean diameter and zeta potential for NP were 299±32 nm (polydispersity index [PI] 0.049) and 11.5±1.1 mV, respectively. Those for QA-Ch-MCD/DEX were 2.7±0.4 nm (PI 0.048) and 6.7±0.6 mV. QA-Ch-MCD/DEX solutions and corresponding NP dispersions were compared in vitro for water-assisted transport through mucus, DEX permeation through excised rat intestine, and ex vivo mucoadhesivity. The complex showed higher mucoadhesion and lower transport rate through mucus; also, it provided faster drug permeation across excised rat intestine. Conclusion Carrier adhesion to mucus surface has played a most important role in favoring transepithelial permeation. Then, within the concerns of the present study, the use of NP seems not to provide any determinant advantage over using the simpler macromolecular complex. PMID:29731628

  1. Host-Guest Engineering of Layered Double Hydroxides towards Efficient Oxygen Evolution Reaction: Recent Advances and Perspectives

    Directory of Open Access Journals (Sweden)

    Jianming Li

    2018-05-01

    Full Text Available Electrochemical water splitting has great potential in the storage of intermittent energy from the sun, wind, or other renewable sources for sustainable clean energy applications. However, the anodic oxygen evolution reaction (OER usually determines the efficiency of practical water electrolysis due to its sluggish four-electron process. Layered double hydroxides (LDHs have attracted increasing attention as one of the ideal and promising electrocatalysts for water oxidation due to their excellent activity, high stability in basic conditions, as well as their earth-abundant compositions. In this review, we discuss the recent progress on LDH-based OER electrocatalysts in terms of active sites, host-guest engineering, and catalytic performances. Moreover, further developments and challenges in developing promising electrocatalysts based on LDHs are discussed from the viewpoint of molecular design and engineering.

  2. Organic light-emitting diodes for lighting: High color quality by controlling energy transfer processes in host-guest-systems

    Science.gov (United States)

    Weichsel, Caroline; Reineke, Sebastian; Furno, Mauro; Lüssem, Björn; Leo, Karl

    2012-02-01

    Exciton generation and transfer processes in a multilayer organic light-emitting diode (OLED) are studied in order to realize OLEDs with warm white color coordinates and high color-rendering index (CRI). We investigate a host-guest-system containing four phosphorescent emitters and two matrix materials with different transport properties. We show, by time-resolved spectroscopy, that an energy back-transfer from the blue emitter to the matrix materials occurs, which can be used to transport excitons to the other emitter molecules. Furthermore, we investigate the excitonic and electronic transfer processes by designing suitable emission layer stacks. As a result, we obtain an OLED with Commission Internationale de lÉclairage (CIE) coordinates of (0.444;0.409), a CRI of 82, and a spectrum independent of the applied current. The OLED shows an external quantum efficiency of 10% and a luminous efficacy of 17.4 lm/W at 1000 cd/m2.

  3. Synthesis and Self-Assembly of Amphiphilic Triblock Terpolymers with Complex Macromolecular Architecture

    KAUST Repository

    Polymeropoulos, George; Zapsas, George; Hadjichristidis, Nikolaos; Avgeropoulos, Apostolos

    2015-01-01

    Two star triblock terpolymers (PS-b-P2VP-b-PEO)3 and one dendritic-like terpolymer [PS-b-P2VP-b-(PEO)2]3 of PS (polystyrene), P2VP (poly(2-vinylpyridine)), and PEO (poly(ethylene oxide)), never reported before, were synthesized by combining atom transfer radical and anionic polymerizations. The synthesis involves the transformation of the -Br groups of the previously reported Br-terminated 3-arm star diblock copolymers to one or two -OH groups, followed by anionic polymerization of ethylene oxide to afford the star or dendritic structure, respectively. The well-defined structure of the terpolymers was confirmed by static light scattering, size exclusion chromatography, and NMR spectroscopy. The self-assembly in solution and the morphology in bulk of the terpolymers, studied by dynamic light scattering and transmission electron microscopy, respectively, reveal new insights in the phase separation of these materials with complex macromolecular architecture. © 2015 American Chemical Society.

  4. Synthesis and Self-Assembly of Amphiphilic Triblock Terpolymers with Complex Macromolecular Architecture

    KAUST Repository

    Polymeropoulos, George

    2015-11-25

    Two star triblock terpolymers (PS-b-P2VP-b-PEO)3 and one dendritic-like terpolymer [PS-b-P2VP-b-(PEO)2]3 of PS (polystyrene), P2VP (poly(2-vinylpyridine)), and PEO (poly(ethylene oxide)), never reported before, were synthesized by combining atom transfer radical and anionic polymerizations. The synthesis involves the transformation of the -Br groups of the previously reported Br-terminated 3-arm star diblock copolymers to one or two -OH groups, followed by anionic polymerization of ethylene oxide to afford the star or dendritic structure, respectively. The well-defined structure of the terpolymers was confirmed by static light scattering, size exclusion chromatography, and NMR spectroscopy. The self-assembly in solution and the morphology in bulk of the terpolymers, studied by dynamic light scattering and transmission electron microscopy, respectively, reveal new insights in the phase separation of these materials with complex macromolecular architecture. © 2015 American Chemical Society.

  5. Selectivity and stoichiometry boosting of beta-cyclodextrin in cationic/anionic surfactant systems: when host-guest equilibrium meets biased aggregation equilibrium.

    Science.gov (United States)

    Jiang, Lingxiang; Yu, Caifang; Deng, Manli; Jin, Changwen; Wang, Yilin; Yan, Yun; Huang, Jianbin

    2010-02-18

    Cationic surfactant/anionic surfactant/beta-CD ternary aqueous systems provide a platform for the coexistence of the host-guest (beta-CD/surfactant) equilibrium and the biased aggregation (monomeric/aggregated surfactants) equilibrium. We report here that the interplay between the two equilibria dominates the systems as follows. (1) The biased aggregation equilibrium imposes an apparent selectivity on the host-guest equilibrium, namely, beta-CD has to always selectively bind the major surfactant (molar fraction > 0.5) even if binding constants of beta-CD to the pair of surfactants are quite similar. (2) In return, the host-guest equilibrium amplifies the bias of the aggregation equilibrium, that is, the selective binding partly removes the major surfactant from the aggregates and leaves the aggregate composition approaching the electroneutral mixing stoichiometry. (3) This composition variation enhances electrostatic attractions between oppositely charged surfactant head groups, thus resulting in less-curved aggregates. In particular, the present apparent host-guest selectivity is of remarkably high values, and the selectivity stems from the bias of the aggregation equilibrium rather than the difference in binding constants. Moreover, beta-CD is defined as a "stoichiometry booster" for the whole class of cationic/anionic surfactant systems, which provides an additional degree of freedom to directly adjust aggregate compositions of the systems. The stoichiometry boosting of the compositions can in turn affect or even determine microstructures and macroproperties of the systems.

  6. The use of workflows in the design and implementation of complex experiments in macromolecular crystallography

    International Nuclear Information System (INIS)

    Brockhauser, Sandor; Svensson, Olof; Bowler, Matthew W.; Nanao, Max; Gordon, Elspeth; Leal, Ricardo M. F.; Popov, Alexander; Gerring, Matthew; McCarthy, Andrew A.; Gotz, Andy

    2012-01-01

    A powerful and easy-to-use workflow environment has been developed at the ESRF for combining experiment control with online data analysis on synchrotron beamlines. This tool provides the possibility of automating complex experiments without the need for expertise in instrumentation control and programming, but rather by accessing defined beamline services. The automation of beam delivery, sample handling and data analysis, together with increasing photon flux, diminishing focal spot size and the appearance of fast-readout detectors on synchrotron beamlines, have changed the way that many macromolecular crystallography experiments are planned and executed. Screening for the best diffracting crystal, or even the best diffracting part of a selected crystal, has been enabled by the development of microfocus beams, precise goniometers and fast-readout detectors that all require rapid feedback from the initial processing of images in order to be effective. All of these advances require the coupling of data feedback to the experimental control system and depend on immediate online data-analysis results during the experiment. To facilitate this, a Data Analysis WorkBench (DAWB) for the flexible creation of complex automated protocols has been developed. Here, example workflows designed and implemented using DAWB are presented for enhanced multi-step crystal characterizations, experiments involving crystal reorientation with kappa goniometers, crystal-burning experiments for empirically determining the radiation sensitivity of a crystal system and the application of mesh scans to find the best location of a crystal to obtain the highest diffraction quality. Beamline users interact with the prepared workflows through a specific brick within the beamline-control GUI MXCuBE

  7. C,N-2-[(Dimethylamino)methyl]phenylplatinum Complexes Functionalized with C60 as Macromolecular Building Blocks

    NARCIS (Netherlands)

    Koten, G. van; Meijer, M.D.; Wolf, E. de; Lutz, M.H.; Spek, A.L.; Klink, G.P.M. van

    2001-01-01

    The application of platinum(II) complexes based on the N,N-dimethylbenzylamine ligand (abbreviated as H-C,N) in macromolecular synthesis was demonstrated. Two cationic C,N-platinum moieties were linked with a 4,4'-bipyridine bridge, giving [{C6H4(CH2NMe2)-2-Pt(PPh3)}2(4,4'-bpy)](BF4)2 (2), the

  8. Spatial, Hysteretic, and Adaptive Host-Guest Chemistry in a Metal-Organic Framework with Open Watson-Crick Sites.

    Science.gov (United States)

    Cai, Hong; Li, Mian; Lin, Xiao-Rong; Chen, Wei; Chen, Guang-Hui; Huang, Xiao-Chun; Li, Dan

    2015-09-01

    Biological and artificial molecules and assemblies capable of supramolecular recognition, especially those with nucleobase pairing, usually rely on autonomous or collective binding to function. Advanced site-specific recognition takes advantage of cooperative spatial effects, as in local folding in protein-DNA binding. Herein, we report a new nucleobase-tagged metal-organic framework (MOF), namely ZnBTCA (BTC=benzene-1,3,5-tricarboxyl, A=adenine), in which the exposed Watson-Crick faces of adenine residues are immobilized periodically on the interior crystalline surface. Systematic control experiments demonstrated the cooperation of the open Watson-Crick sites and spatial effects within the nanopores, and thermodynamic and kinetic studies revealed a hysteretic host-guest interaction attributed to mild chemisorption. We further exploited this behavior for adenine-thymine binding within the constrained pores, and a globally adaptive response of the MOF host was observed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Host-Guest Interaction between Herbicide Oxadiargyl and Hydroxypropyl- β -Cyclodextrin

    Directory of Open Access Journals (Sweden)

    Sofia Benfeito

    2013-01-01

    Full Text Available In the face of a growing human population and increased urbanization, the demand for pesticides will simply rise. Farmers must escalate yields on increasingly fewer farm acres. However, the risks of pesticides, whether real or perceived, may force changes in the way these chemicals are used. Scientists are working toward pest control plans that are environmentally sound, effective, and profitable. In this context the development of new pesticide formulations which may improve application effectiveness, safety, handling, and storage can be pointed out as a solution. As a contribution to the area, the microencapsulation of the herbicide oxadiargyl (OXA in (2-hydroxypropyl-β-cyclodextrin (HP-β-CD was performed. The study was conducted in different aqueous media (ultrapure water and in different pH buffer solutions. In all cases an increment of the oxadiargyl solubility as a function of the HP-β-CD concentration that has been related to the formation of an inclusion complex was verified. UV-Vis and NMR experiments allowed concluding that the stoichiometry of the OXA/HP-β-CD complex formed is 1 : 1. The gathered results can be regarded as an important step for its removal from industrial effluents and/or to increase the stabilizing action, encapsulation, and adsorption in water treatment plants.

  10. Molecular recognition: Comparative study of a tunable host-guest system by using a fluorescent model system and collision-induced dissociation mass spectrometry on dendrimers

    DEFF Research Database (Denmark)

    Pittelkow, M.; Nielsen, C.B.; Broeren, A.C.

    2005-01-01

    Host-guest interactions between the periphery of adamantylurea-functionalized dendrimers (host) and ureido acetic acid derivatives (guest) were shown to be specific, strong and spatially well-defined. The binding becomes stronger when using phosphonic or sulfonic acid derivatives. In the present...... work we have quantified the binding constants for the host-guest interactions between two different host motifs and six different guest molecules. The host molecules, which resemble the periphery of a poly(propylene imine) dendrimer, have been fitted with an anthracene-based fluorescent probe. The two...... host motifs differ in terms of the length of the spacer between a tertiary amine and two ureido functionalities. The guest molecules all contain an acidic moiety (either a carboxylic acid, a phosphonic acid, or a sulfonic acid) and three of them also contain an ureido moiety capable of forming multiple...

  11. A concept for the removal of microplastics from the marine environment with innovative host-guest relationships.

    Science.gov (United States)

    Herbort, Adrian Frank; Schuhen, Katrin

    2017-04-01

    Environmental pollution caused by inert anthropogenic stressors such as microplastics in aquatic media is constantly increasing. Through the proliferating use of plastic products in daily life, more and more plastic particles enter waters as primary microplastics. Even though large scale plastic items such as plastic bottles and bags represent the highest percentage of plastic waste, their degeneration also generates microparticles and nanoparticles (secondary microplastics). Modern sewage treatment plants require innovative ideas in order to deal with this man-made problem. State-of-the-art technology offers approaches to minimise the amount of microplastics in aquatic systems. These technologies, however, are either insufficient or very costly, as well as time-consuming in both cases. The conceptual idea presented here is to apply innovative inorganic-organic hybrid silica gels which provide a cost-effective and straightforward approach. Currently, the synthesis of preorganised bioinspired compounds is advancing in order to produce functionalised hybrid silica gels in a further step. These gels have the ability to remove stressors such as microplastics from waste water. By means of the sol-gel process, bioinspired silane compounds are currently being permuted to macromolecules and examined with respect to their properties as fixation and filter material in order to remove the hydrophobic anthropogenic stressors sustainably. Here, the reproduction of biological systems plays a significant role. In particular in material sciences, this approach is becoming increasingly important. Among other concepts, new biomimetic molecules form the basis for the investigation of innovative host-guest relationships for anthropogenic stressors in the environment and their implementation in technical processes.

  12. The macromolecular complex of ICP and falcipain-2 from Plasmodium: preparation, crystallization and preliminary X-ray diffraction analysis

    International Nuclear Information System (INIS)

    Hansen, Guido; Schwarzloh, Britta; Rennenberg, Annika; Heussler, Volker T.; Hilgenfeld, Rolf

    2011-01-01

    The macromolecular complex of ICP (inhibitor of cysteine proteases) from P. berghei and falcipain-2 from P. falciparum has been prepared and crystallized, and a diffraction data set has been collected to a resolution of 2.6 Å. The malaria parasite Plasmodium depends on the tight control of cysteine-protease activity throughout its life cycle. Recently, the characterization of a new class of potent inhibitors of cysteine proteases (ICPs) secreted by Plasmodium has been reported. Here, the recombinant production, purification and crystallization of the inhibitory C-terminal domain of ICP from P. berghei in complex with the P. falciparum haemoglobinase falcipain-2 is described. The 1:1 complex was crystallized in space group P4 3 , with unit-cell parameters a = b = 71.15, c = 120.09 Å. A complete diffraction data set was collected to a resolution of 2.6 Å

  13. Macromolecular therapeutics.

    Science.gov (United States)

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Constructing irregular surfaces to enclose macromolecular complexes for mesoscale modeling using the discrete surface charge optimization (DISCO) algorithm.

    Science.gov (United States)

    Zhang, Qing; Beard, Daniel A; Schlick, Tamar

    2003-12-01

    Salt-mediated electrostatics interactions play an essential role in biomolecular structures and dynamics. Because macromolecular systems modeled at atomic resolution contain thousands of solute atoms, the electrostatic computations constitute an expensive part of the force and energy calculations. Implicit solvent models are one way to simplify the model and associated calculations, but they are generally used in combination with standard atomic models for the solute. To approximate electrostatics interactions in models on the polymer level (e.g., supercoiled DNA) that are simulated over long times (e.g., milliseconds) using Brownian dynamics, Beard and Schlick have developed the DiSCO (Discrete Surface Charge Optimization) algorithm. DiSCO represents a macromolecular complex by a few hundred discrete charges on a surface enclosing the system modeled by the Debye-Hückel (screened Coulombic) approximation to the Poisson-Boltzmann equation, and treats the salt solution as continuum solvation. DiSCO can represent the nucleosome core particle (>12,000 atoms), for example, by 353 discrete surface charges distributed on the surfaces of a large disk for the nucleosome core particle and a slender cylinder for the histone tail; the charges are optimized with respect to the Poisson-Boltzmann solution for the electric field, yielding a approximately 5.5% residual. Because regular surfaces enclosing macromolecules are not sufficiently general and may be suboptimal for certain systems, we develop a general method to construct irregular models tailored to the geometry of macromolecules. We also compare charge optimization based on both the electric field and electrostatic potential refinement. Results indicate that irregular surfaces can lead to a more accurate approximation (lower residuals), and the refinement in terms of the electric field is more robust. We also show that surface smoothing for irregular models is important, that the charge optimization (by the TNPACK

  15. An integrated native mass spectrometry and top-down proteomics method that connects sequence to structure and function of macromolecular complexes

    Science.gov (United States)

    Li, Huilin; Nguyen, Hong Hanh; Ogorzalek Loo, Rachel R.; Campuzano, Iain D. G.; Loo, Joseph A.

    2018-02-01

    Mass spectrometry (MS) has become a crucial technique for the analysis of protein complexes. Native MS has traditionally examined protein subunit arrangements, while proteomics MS has focused on sequence identification. These two techniques are usually performed separately without taking advantage of the synergies between them. Here we describe the development of an integrated native MS and top-down proteomics method using Fourier-transform ion cyclotron resonance (FTICR) to analyse macromolecular protein complexes in a single experiment. We address previous concerns of employing FTICR MS to measure large macromolecular complexes by demonstrating the detection of complexes up to 1.8 MDa, and we demonstrate the efficacy of this technique for direct acquirement of sequence to higher-order structural information with several large complexes. We then summarize the unique functionalities of different activation/dissociation techniques. The platform expands the ability of MS to integrate proteomics and structural biology to provide insights into protein structure, function and regulation.

  16. Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.

    Science.gov (United States)

    Orlandi, Cesare; Cao, Yan; Martemyanov, Kirill A

    2013-10-29

    In the mammalian retina, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision, and disruption of this process leads to congenital stationary night blindness in human patients. The ON-bipolar neurons use the metabotropic signaling cascade, initiated by the mGluR6 receptor, to generate depolarizing responses to light-induced changes in neurotransmitter glutamate release from the photoreceptor axonal terminals. Evidence for the identity of the components involved in transducing these signals is growing rapidly. Recently, the orphan receptor, GPR179, a member of the G protein-coupled receptor (GPCR) superfamily, has been shown to be indispensable for the synaptic responses of ON-bipolar cells. In our study, we investigated the interaction of GPR179 with principle components of the signal transduction cascade. We used immunoprecipitation and proximity ligation assays in transfected cells and native retinas to characterize the protein-protein interactions involving GPR179. The influence of cascade components on GPR179 localization was examined through immunohistochemical staining of the retinas from genetic mouse models. We demonstrated that, in mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression. These observations suggest that the mGluR6 signaling cascade is scaffolded as a macromolecular complex in which the interactions between the components ensure the optimal spatiotemporal characteristics of signal transduction.

  17. The costa of trichomonads: A complex macromolecular cytoskeleton structure made of uncommon proteins.

    Science.gov (United States)

    de Andrade Rosa, Ivone; Caruso, Marjolly Brigido; de Oliveira Santos, Eidy; Gonzaga, Luiz; Zingali, Russolina Benedeta; de Vasconcelos, Ana Tereza R; de Souza, Wanderley; Benchimol, Marlene

    2017-06-01

    The costa is a prominent striated fibre that is found in protozoa of the Trichomonadidae family that present an undulating membrane. It is composed primarily of proteins that have not yet been explored. In this study, we used cell fractionation to obtain a highly enriched costa fraction whose structure and composition was further analysed by electron microscopy and mass spectrometry. Electron microscopy of negatively stained samples revealed that the costa, which is a periodic structure with alternating electron-dense and electron-lucent bands, displays three distinct regions, named the head, neck and body. Fourier transform analysis showed that the electron-lucent bands present sub-bands with a regular pattern. An analysis of the costa fraction via one- and two-dimensional electrophoresis and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) allowed the identification of 54 hypothetical proteins. Fourteen of those proteins were considered to be major components of the fraction. The costa of T. foetus is a complex and organised cytoskeleton structure made of a large number of proteins which is assembled into filamentous structures. Some of these proteins exhibit uncharacterised domains and no function related according to gene ontology, suggesting that the costa structure may be formed by a new class of proteins that differ from those previously described in other organisms. Seven of these proteins contain prefoldin domains displaying coiled-coil regions. This propriety is shared with proteins of the striated fibres of other protozoan as well as in intermediate filaments. Our observations suggest the presence of a new class of the cytoskeleton filaments in T. foetus. We believe that our data could auxiliate in determining the specific locations of these proteins in the distinct regions that compose the costa, as well as to define the functional roles of each component. Therefore, our study will help in the better understanding of the

  18. Poly-N-Heterocyclic Carbene Ligands with Polyaromatic Linkers. Self-Assembly and Host-Guest Chemistry

    OpenAIRE

    Mejuto Nieblas, Carmen

    2017-01-01

    In summary, a series of polytopic ligands based on NHC and MIC ligands have been synthesized in this Doctoral Thesis by means of different synthetic routes that gave rise to systems with very sophisticated architectures. A large variety of metal complexes have been formed based on these salt precursors that allowed the preparation of homo and heteroleptic mono-, di- and tri-metal complexes with different geometries. The luminescence properties of various imidazolium salts, the catalytic activ...

  19. A facile metal-free "grafting-from" route from acrylamide-based substrate toward complex macromolecular combs

    KAUST Repository

    Zhao, Junpeng

    2013-01-01

    High-molecular-weight poly(N,N-dimethylacrylamide-co-acrylamide) was used as a model functional substrate to investigate phosphazene base (t-BuP 4)-promoted metal-free anionic graft polymerization utilizing primary amide moieties as initiating sites. The (co)polymerization of epoxides was proven to be effective, leading to macromolecular combs with side chains being single- or double-graft homopolymer, block copolymer and statistical copolymer. © 2013 The Royal Society of Chemistry.

  20. Novel photoluminescence enzyme immunoassay based on supramolecular host-guest recognition using L-arginine/6-aza-2-thiothymine-stabilized gold nanocluster.

    Science.gov (United States)

    Wang, Youmei; Lu, Minghua; Tang, Dianping

    2018-06-30

    A new photoluminescence (PL) enzyme immunoassay was designed for sensitive detection of aflatoxin B 1 (AFB 1 ) via an innovative enzyme substrate, 6-aza-2-thiothymine-stabilized gold nanocluster (AAT-AuNC) with L-arginine. The enzyme substrate with strong PL intensity was formed through supramolecular host-guest assembly between guanidine group of L-arginine and AAT capped on the surface of AuNC. Upon arginase introduction, the captured L-arginine was hydrolyzed into ornithine and urea, thus resulting in the decreasing PL intensity. Based on this principle, a novel competitive-type immunoreaction was first carried out on AFB 1 -bovine serum albumin (AFB 1 -BSA) conjugate-coated microplate, using arginase-labeled anti-AFB 1 antibody as the competitor. Under the optimum conditions, the PL intensity increased with the increment of target AFB 1 , and allowed the detection of the analyte at concentrations as low as 3.2 pg mL -1 (ppt). Moreover, L-arginine-AAT-AuNC-based PL enzyme immunoassay afforded good reproducibility and acceptable specificity. In addition, the accuracy of this methodology, referring to commercial AFB 1 ELISA kit, was evaluated to analyze naturally contaminated or spiked peanut samples, giving well-matched results between two methods, thus representing a useful scheme for practical application in quantitative monitoring of mycotoxins in foodstuff. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Microcalorimetric and spectrographic studies on host-guest interactions of {alpha}-, {beta}-, {gamma}- and M{beta}-cyclodextrin with resveratrol

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui; Xu, Xiangyu; Liu, Min [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China); Sun, Dezhi, E-mail: sundezhisdz@163.com [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China); Li, Linwei, E-mail: lilinwei@lcu.edu.cn [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China)

    2010-10-20

    Thermal effects of inclusion processes of {alpha}-, {beta}-, {gamma}- and M{beta}-cyclodextrin with resveratrol (RES) in aqueous solutions were determined by isothermal titration calorimetry (ITC) with nanowatt sensitivity at the temperature of 298.15 K. Standard enthalpy changes, stoichiometry and equilibrium constants of the inclusion complexes were derived from the direct calorimetric data utilizing nonlinear simulation. The thermodynamic parameters were discussed in the light of weak interactions between the host and the guest molecules combining with UV spectral message. The results indicate that all of the complexes formed in the aqueous solutions are in 1:1 stoichiometry. The binding processes of {alpha}-, {beta}- and M{beta}-cyclodextrin with the guest are mainly driven by enthalpy, while that of {gamma}-cyclodextrin with the drug is driven by both enthalpy and entropy.

  2. Smart SERS Hot Spots: Single Molecules Can Be Positioned in a Plasmonic Nanojunction Using Host-Guest Chemistry.

    Science.gov (United States)

    Kim, Nam Hoon; Hwang, Wooseup; Baek, Kangkyun; Rohman, Md Rumum; Kim, Jeehong; Kim, Hyun Woo; Mun, Jungho; Lee, So Young; Yun, Gyeongwon; Murray, James; Ha, Ji Won; Rho, Junsuk; Moskovits, Martin; Kim, Kimoon

    2018-04-04

    Single-molecule surface-enhanced Raman spectroscopy (SERS) offers new opportunities for exploring the complex chemical and biological processes that cannot be easily probed using ensemble techniques. However, the ability to place the single molecule of interest reliably within a hot spot, to enable its analysis at the single-molecule level, remains challenging. Here we describe a novel strategy for locating and securing a single target analyte in a SERS hot spot at a plasmonic nanojunction. The "smart" hot spot was generated by employing a thiol-functionalized cucurbit[6]uril (CB[6]) as a molecular spacer linking a silver nanoparticle to a metal substrate. This approach also permits one to study molecules chemically reluctant to enter the hot spot, by conjugating them to a moiety, such as spermine, that has a high affinity for CB[6]. The hot spot can accommodate at most a few, and often only a single, analyte molecule. Bianalyte experiments revealed that one can reproducibly treat the SERS substrate such that 96% of the hot spots contain a single analyte molecule. Furthermore, by utilizing a series of molecules each consisting of spermine bound to perylene bisimide, a bright SERS molecule, with polymethylene linkers of varying lengths, the SERS intensity as a function of distance from the center of the hot spot could be measured. The SERS enhancement was found to decrease as 1 over the square of the distance from the center of the hot spot, and the single-molecule SERS cross sections were found to increase with AgNP diameter.

  3. Carborane-beta-cyclodextrin complexes as a supramolecular connector for bioactive surfaces

    Czech Academy of Sciences Publication Activity Database

    Neirynck, P.; Schimer, Jiří; Jonkheijm, P.; Milroy, L. G.; Cígler, Petr; Brunsveld, L.

    2015-01-01

    Roč. 3, č. 4 (2015), s. 539-545 ISSN 2050-750X R&D Projects: GA MŠk(CZ) LH11027 Institutional support: RVO:61388963 Keywords : beta-cyclodextrine/carborane host-guest system * supramolecular chemistry * bioactive surfaces Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.872, year: 2015 http://pubs.rsc.org/en/content/articlepdf/2015/tb/c4tb01489h

  4. Inclusion complexation of tetrabutylammonium iodide by cyclodextrins

    Indian Academy of Sciences (India)

    Biswajit Datta

    Host-guest inclusion complex of an ionic solid (tetrabutyl ammonium iodide) with α- and β- cyclodextrin has been ... tions.2 CDs are cyclic oligomer of α-D-glucose having numerous of ... of locating at the interface of two phases (liquid–liquid.

  5. Synthesis of novel complexing macromolecular surfactants and study of their interactions with cobalt for the development of a decontamination process of textiles in dense CO2 medium

    International Nuclear Information System (INIS)

    Chirat, M.

    2012-01-01

    This study is about textile decontamination in dense CO 2 (liquid CO 2 or supercritical CO 2 ). The study is carried out in the framework of decontamination of textile used in the nuclear industry. The dense CO 2 offers an alternative to aqueous medium used in the current process which generates a huge quantity of contaminated aqueous effluent requiring a post-treatment. Cobalt is the targeted contamination and can be found as ionic species or particles. The cobalt extraction in dense CO 2 is achieved with an additive: a complexing CO 2 -philic/CO 2 -phobic macromolecular surfactant. Several types of additives were synthesized by controlled free radical polymerization: gradient copolymers made with CO 2 -philic groups (silicone-based or fluorinated moieties) and CO 2 -phobic complexing groups (aceto acetoxy, di-ethylphosphonate or phosphonic acid moieties). The copolymer behavior in dense CO 2 was determined by phase diagram measurements (cloud point method) and their self-assembly in dense CO 2 was investigated by small angle neutron scattering. The fluorinated copolymers were found advantageous in terms of solubility. Nevertheless, the silicone-based copolymers showed solubilities which are compatible with the process, therefore they are a good alternative to avoid fluorinated compounds which are unwanted in the conditioning of nuclear wastes. The study of cobalt complexation by the copolymers (UV-vis spectroscopy and inductively coupled plasma-mass spectroscopy) established relations between the type of complexing group and the affinity with the cobalt. The solubility of copolymer-cobalt complexes in dense CO 2 is similar to those of copolymers. Moreover, the self-assembly study of the complex revealed a low aggregation. Finally, the synthesized copolymers were used in particle or ionic decontamination processes. In the case of ionic decontamination process, a rate of 70% of decontamination was reached with the use of gradient copolymer poly(1

  6. Copolymers containing phosphorescent iridium(III) complexes obtained by free and controlled radical polymerization techniques

    NARCIS (Netherlands)

    Ulbricht, C.; Becer, C.R.; Winter, A.; Veldman, D.; Schubert, U.S.

    2008-01-01

    A methacrylate-functionalized phosphorescent Ir(III)-complex has been synthesized, characterized, and applied as a monomer in radical copolymerizations. Together with methyl methacrylate, the complex has been copolymerized under free radical polymerization conditions. Aiming for host-guest-systems,

  7. Practical macromolecular cryocrystallography

    Energy Technology Data Exchange (ETDEWEB)

    Pflugrath, J. W., E-mail: jim.pflugrath@gmail.com [Rigaku Americas Corp., 9009 New Trails Drive, The Woodlands, TX 77381 (United States)

    2015-05-27

    Current methods, reagents and experimental hardware for successfully and reproducibly flash-cooling macromolecular crystals to cryogenic temperatures for X-ray diffraction data collection are reviewed. Cryocrystallography is an indispensable technique that is routinely used for single-crystal X-ray diffraction data collection at temperatures near 100 K, where radiation damage is mitigated. Modern procedures and tools to cryoprotect and rapidly cool macromolecular crystals with a significant solvent fraction to below the glass-transition phase of water are reviewed. Reagents and methods to help prevent the stresses that damage crystals when flash-cooling are described. A method of using isopentane to assess whether cryogenic temperatures have been preserved when dismounting screened crystals is also presented.

  8. Macromolecular crystallization in microgravity

    International Nuclear Information System (INIS)

    Snell, Edward H; Helliwell, John R

    2005-01-01

    Density difference fluid flows and sedimentation of growing crystals are greatly reduced when crystallization takes place in a reduced gravity environment. In the case of macromolecular crystallography a crystal of a biological macromolecule is used for diffraction experiments (x-ray or neutron) so as to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal then the greater the molecular structure detail that can be extracted. It is this structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences, with major potential in understanding disease pathologies. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyse the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural advances. Finally, limitations and alternatives to microgravity and future directions for this research are covered. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry and mathematics meet to enable insight to the fundamentals of life. As the reader will see, there is a great deal of physics involved when the microgravity environment is applied to crystallization, some of it known, and undoubtedly much yet to

  9. Tuning of Magnetic Anisotropy in Hexairon(III) Rings by Host-Guest Interactions: An Investigation by High-Field Torque Magnetometry.

    Science.gov (United States)

    Cornia; Affronte; Jansen; Abbati; Gatteschi

    1999-08-01

    Full chemical control of magnetic anisotropy in hexairon(III) rings can be achieved by varying the size of the guest alkali metal ion. Dramatically different anisotropies characterize the Li(I) and Na(I) complexes of [Fe(6)(OMe)(12)(L)(6)] (L=1,3-propanedione derivatives; a schematic representation of the Li(I) complex is shown), as revealed by high-field torque magnetometry-Iron: (g), oxygen: o, carbon: o, Li(+): plus sign in circle.

  10. Optimizing Water Exchange Rates and Rotational Mobility for High-Relaxivity of a Novel Gd-DO3A Derivative Complex Conjugated to Inulin as Macromolecular Contrast Agents for MRI.

    Science.gov (United States)

    Granato, Luigi; Vander Elst, Luce; Henoumont, Celine; Muller, Robert N; Laurent, Sophie

    2018-02-01

    Thanks to the understanding of the relationships between the residence lifetime τ M of the coordinated water molecules to macrocyclic Gd-complexes and the rotational mobility τ R of these structures, and according to the theory for paramagnetic relaxation, it is now possible to design macromolecular contrast agents with enhanced relaxivities by optimizing these two parameters through ligand structural modification. We succeeded in accelerating the water exchange rate by inducing steric compression around the water binding site, and by removing the amide function from the DOTA-AA ligand [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(p-aminoanilide)] (L) previously designed. This new ligand 10[2(1-oxo-1-p-propylthioureidophenylpropyl]-1,4,7,10-tetraazacyclodecane-1,4,7-tetraacetic acid (L 1 ) was then covalently conjugated to API [O-(aminopropyl)inulin] to get the complex API-(GdL 1 )x with intent to slow down the rotational correlation time (τ R ) of the macromolecular complex. The evaluation of the longitudinal relaxivity at different magnetic fields and the study of the 17 O-NMR at variable temperature of the low-molecular-weight compound (GdL 1 ) showed a slight decrease of the τ M value (τM310 = 331 ns vs. τM310 = 450 ns for the GdL complex). Consequently to the increase of the size of the API-(GdL 1 )x complex, the rotational correlation time becomes about 360 times longer compared to the monomeric GdL 1 complex (τ R  = 33,700 ps), which results in an enhanced proton relaxivity. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

  11. In silico properties characterization of water-soluble γ-cyclodextrin bi-capped C60 complex

    DEFF Research Database (Denmark)

    Cao, Ruyin; Wu, Shanshan

    2015-01-01

    Cyclodextrin-related host-guest encapsulation is pivotal to modulate the solubility of C60, thereby promoting its potential therapeutic applications. Here we present a computational study on γ-cyclodextrin bi-capped C60 complex, probing characteristics for all the possible stoichiometry in aqueou...

  12. In situ macromolecular crystallography using microbeams.

    Science.gov (United States)

    Axford, Danny; Owen, Robin L; Aishima, Jun; Foadi, James; Morgan, Ann W; Robinson, James I; Nettleship, Joanne E; Owens, Raymond J; Moraes, Isabel; Fry, Elizabeth E; Grimes, Jonathan M; Harlos, Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S; Stuart, David I; Evans, Gwyndaf

    2012-05-01

    Despite significant progress in high-throughput methods in macromolecular crystallography, the production of diffraction-quality crystals remains a major bottleneck. By recording diffraction in situ from crystals in their crystallization plates at room temperature, a number of problems associated with crystal handling and cryoprotection can be side-stepped. Using a dedicated goniometer installed on the microfocus macromolecular crystallography beamline I24 at Diamond Light Source, crystals have been studied in situ with an intense and flexible microfocus beam, allowing weakly diffracting samples to be assessed without a manual crystal-handling step but with good signal to noise, despite the background scatter from the plate. A number of case studies are reported: the structure solution of bovine enterovirus 2, crystallization screening of membrane proteins and complexes, and structure solution from crystallization hits produced via a high-throughput pipeline. These demonstrate the potential for in situ data collection and structure solution with microbeams. © 2012 International Union of Crystallography

  13. Ultrafast energy transfer in dansylated POPAM--eosin complexes

    Science.gov (United States)

    Aumanen, Jukka; Lehtovuori, Viivi; Werner, Nicole; Richardt, Gabriele; van Heyst, Jeroen; Vögtle, Fritz; Korppi-Tommola, Jouko

    2006-12-01

    Excitation energy transfer (EET) in dendritic host-guest complexes has been studied. Three generations G2, G3 and G4 of dansyl substituted poly(propyleneamine) dendrimers (POPAM) were complexed with a fluorescent dye eosin in chloroform solution. Arrival of excitation from dansyls to eosin was monitored by femtosecond transient absorption spectroscopy. EET rates from the dansyls to eosin(s) are characterised by two time constants 1 ps and 6 ps independent of dendrimer generation. Relaxation processes in eosin were clearly faster when complexed with dendrimer than in solution. As several eosins are bound to G3 and G4 dendrimers, besides host-guest interaction, also eosin-eosin interactions may contribute to the faster relaxation observed in these complexes.

  14. Macromolecular crystallography using synchrotron radiation

    International Nuclear Information System (INIS)

    Bartunik, H.D.; Phillips, J.C.; Fourme, R.

    1982-01-01

    The use of synchrotron X-ray sources in macromolecular crystallography is described. The properties of synchrotron radiation relevant to macromolecular crystallography are examined. The applications discussed include anomalous dispersion techniques, the acquisition of normal and high resolution data, and kinetic studies of structural changes in macromolecules; protein data are presented illustrating these applications. The apparatus used is described including information on the electronic detectors, the monitoring of the incident beam and crystal cooling. (U.K.)

  15. Accurate characterization of weak macromolecular interactions by titration of NMR residual dipolar couplings: application to the CD2AP SH3-C:ubiquitin complex.

    Science.gov (United States)

    Ortega-Roldan, Jose Luis; Jensen, Malene Ringkjøbing; Brutscher, Bernhard; Azuaga, Ana I; Blackledge, Martin; van Nuland, Nico A J

    2009-05-01

    The description of the interactome represents one of key challenges remaining for structural biology. Physiologically important weak interactions, with dissociation constants above 100 muM, are remarkably common, but remain beyond the reach of most of structural biology. NMR spectroscopy, and in particular, residual dipolar couplings (RDCs) provide crucial conformational constraints on intermolecular orientation in molecular complexes, but the combination of free and bound contributions to the measured RDC seriously complicates their exploitation for weakly interacting partners. We develop a robust approach for the determination of weak complexes based on: (i) differential isotopic labeling of the partner proteins facilitating RDC measurement in both partners; (ii) measurement of RDC changes upon titration into different equilibrium mixtures of partially aligned free and complex forms of the proteins; (iii) novel analytical approaches to determine the effective alignment in all equilibrium mixtures; and (iv) extraction of precise RDCs for bound forms of both partner proteins. The approach is demonstrated for the determination of the three-dimensional structure of the weakly interacting CD2AP SH3-C:Ubiquitin complex (K(d) = 132 +/- 13 muM) and is shown, using cross-validation, to be highly precise. We expect this methodology to extend the remarkable and unique ability of NMR to study weak protein-protein complexes.

  16. Recent advances in macromolecular prodrugs

    DEFF Research Database (Denmark)

    Riber, Camilla Frich; Zelikin, Alexander N.

    2017-01-01

    Macromolecular prodrugs (MP) are high molar mass conjugates, typically carrying several copies of a drug or a drug combination, designed to optimize delivery of the drug, that is — its pharmacokinetics. From its advent several decades ago, design of MP has undergone significant development and es...

  17. Control of Macromolecular Architectures for Renewable Polymers: Case Studies

    Science.gov (United States)

    Tang, Chuanbing

    The development of sustainable polymers from nature biomass is growing, but facing fierce competition from existing petrochemical-based counterparts. Controlling macromolecular architectures to maximize the properties of renewable polymers is a desirable approach to gain advantages. Given the complexity of biomass, there needs special consideration other than traditional design. In the presentation, I will talk about a few case studies on how macromolecular architectures could tune the properties of sustainable bioplastics and elastomers from renewable biomass such as resin acids (natural rosin) and plant oils.

  18. In situ macromolecular crystallography using microbeams

    Energy Technology Data Exchange (ETDEWEB)

    Axford, Danny; Owen, Robin L.; Aishima, Jun [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Foadi, James [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Morgan, Ann W.; Robinson, James I. [University of Leeds, Leeds LS9 7FT (United Kingdom); Nettleship, Joanne E.; Owens, Raymond J. [Research Complex at Harwell, Rutherford Appleton Laboratory R92, Didcot, Oxfordshire OX11 0DE (United Kingdom); Moraes, Isabel [Imperial College, London SW7 2AZ (United Kingdom); Fry, Elizabeth E.; Grimes, Jonathan M.; Harlos, Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S. [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Stuart, David I. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Evans, Gwyndaf, E-mail: gwyndaf.evans@diamond.ac.uk [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

    2012-04-17

    A sample environment for mounting crystallization trays has been developed on the microfocus beamline I24 at Diamond Light Source. The technical developments and several case studies are described. Despite significant progress in high-throughput methods in macromolecular crystallography, the production of diffraction-quality crystals remains a major bottleneck. By recording diffraction in situ from crystals in their crystallization plates at room temperature, a number of problems associated with crystal handling and cryoprotection can be side-stepped. Using a dedicated goniometer installed on the microfocus macromolecular crystallography beamline I24 at Diamond Light Source, crystals have been studied in situ with an intense and flexible microfocus beam, allowing weakly diffracting samples to be assessed without a manual crystal-handling step but with good signal to noise, despite the background scatter from the plate. A number of case studies are reported: the structure solution of bovine enterovirus 2, crystallization screening of membrane proteins and complexes, and structure solution from crystallization hits produced via a high-throughput pipeline. These demonstrate the potential for in situ data collection and structure solution with microbeams.

  19. In situ macromolecular crystallography using microbeams

    International Nuclear Information System (INIS)

    Axford, Danny; Owen, Robin L.; Aishima, Jun; Foadi, James; Morgan, Ann W.; Robinson, James I.; Nettleship, Joanne E.; Owens, Raymond J.; Moraes, Isabel; Fry, Elizabeth E.; Grimes, Jonathan M.; Harlos, Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S.; Stuart, David I.; Evans, Gwyndaf

    2012-01-01

    A sample environment for mounting crystallization trays has been developed on the microfocus beamline I24 at Diamond Light Source. The technical developments and several case studies are described. Despite significant progress in high-throughput methods in macromolecular crystallography, the production of diffraction-quality crystals remains a major bottleneck. By recording diffraction in situ from crystals in their crystallization plates at room temperature, a number of problems associated with crystal handling and cryoprotection can be side-stepped. Using a dedicated goniometer installed on the microfocus macromolecular crystallography beamline I24 at Diamond Light Source, crystals have been studied in situ with an intense and flexible microfocus beam, allowing weakly diffracting samples to be assessed without a manual crystal-handling step but with good signal to noise, despite the background scatter from the plate. A number of case studies are reported: the structure solution of bovine enterovirus 2, crystallization screening of membrane proteins and complexes, and structure solution from crystallization hits produced via a high-throughput pipeline. These demonstrate the potential for in situ data collection and structure solution with microbeams

  20. Photophysical Properties and Photoinduced Electron Transfer Within Host-Guest Complexes of 5,10,15,20-Tetrakis(4-N-methylpyridyl)porphyrin with Water-soluble Calixarenes and Cyclodextrins

    Czech Academy of Sciences Publication Activity Database

    Lang, Kamil; Kubát, Pavel; Lhoták, P.; Mosinger, J.; Wagnerová, Dana Marie

    2001-01-01

    Roč. 74, č. 4 (2001), s. 558-565 ISSN 0031-8655 R&D Projects: GA ČR GA203/99/1163 Institutional research plan: CEZ:AV0Z4032918 Keywords : ammonium cations * porphyrin dimers * binding Subject RIV: CA - Inorganic Chemistry Impact factor: 2.146, year: 2001

  1. Host-Guest Inclusion Complexes between Amlodipine Enantiomers in Biphasic Recognition Chiral Extraction System using Tartaric Acid and β-Cyclodextrin Derivatives as Positive Confirmation Using of their Enantioselective Extraction

    OpenAIRE

    AZZAM, Khaldun; ABDALLAH, Hassan; HALIM, Hairul; AHMAD, Maizatul; SHAIBAH, Hassan

    2015-01-01

    The current work reports an extended theoretical study from our previous experimental work for the enantioselective extraction of amlodipine enantiomers in a biphasic recognition chiral extraction system (BRCES) consisting of hydrophobic D-diisopropyl tartrate dissolved in organic phase (n-decanol) and hydrophilic hydroxypropyl-?-cyclodextrin (HP-?-CD) in aqueous phase (acetate buffer) which preferentially recognize the R-enantiomer and S-enantiomer, respectively. The calculations were simula...

  2. Structure studies of macromolecular systems

    Czech Academy of Sciences Publication Activity Database

    Hašek, Jindřich; Dohnálek, Jan; Skálová, Tereza; Dušková, Jarmila; Kolenko, Petr

    2006-01-01

    Roč. 13, č. 3 (2006), s. 136 ISSN 1211-5894. [Czech and Slovak Crystallographic Colloquium. 22.06.2006-24.06.2006, Grenoble] R&D Projects: GA AV ČR IAA4050811; GA MŠk 1K05008 Keywords : structure * X-ray diffraction * synchrotron Subject RIV: CD - Macromolecular Chemistry http://www. xray .cz/ms/default.htm

  3. Isotope labeling for NMR studies of macromolecular structure and interactions

    International Nuclear Information System (INIS)

    Wright, P.E.

    1994-01-01

    Implementation of biosynthetic methods for uniform or specific isotope labeling of proteins, coupled with the recent development of powerful heteronuclear multidimensional NMR methods, has led to a dramatic increase in the size and complexity of macromolecular systems that are now amenable to NMR structural analysis. In recent years, a new technology has emerged that combines uniform 13 C, 15 N labeling with heteronuclear multidimensional NMR methods to allow NMR structural studies of systems approaching 25 to 30 kDa in molecular weight. In addition, with the introduction of specific 13 C and 15 N labels into ligands, meaningful NMR studies of complexes of even higher molecular weight have become feasible. These advances usher in a new era in which the earlier, rather stringent molecular weight limitations have been greatly surpassed and NMR can begin to address many central biological problems that involve macromolecular structure, dynamics, and interactions

  4. Isotope labeling for NMR studies of macromolecular structure and interactions

    Energy Technology Data Exchange (ETDEWEB)

    Wright, P.E. [Scripps Research Institute, La Jolla, CA (United States)

    1994-12-01

    Implementation of biosynthetic methods for uniform or specific isotope labeling of proteins, coupled with the recent development of powerful heteronuclear multidimensional NMR methods, has led to a dramatic increase in the size and complexity of macromolecular systems that are now amenable to NMR structural analysis. In recent years, a new technology has emerged that combines uniform {sup 13}C, {sup 15}N labeling with heteronuclear multidimensional NMR methods to allow NMR structural studies of systems approaching 25 to 30 kDa in molecular weight. In addition, with the introduction of specific {sup 13}C and {sup 15}N labels into ligands, meaningful NMR studies of complexes of even higher molecular weight have become feasible. These advances usher in a new era in which the earlier, rather stringent molecular weight limitations have been greatly surpassed and NMR can begin to address many central biological problems that involve macromolecular structure, dynamics, and interactions.

  5. Macromolecular systems for vaccine delivery.

    Science.gov (United States)

    MuŽíková, G; Laga, R

    2016-10-20

    Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.

  6. Collagen macromolecular drug delivery systems

    International Nuclear Information System (INIS)

    Gilbert, D.L.

    1988-01-01

    The objective of this study was to examine collagen for use as a macromolecular drug delivery system by determining the mechanism of release through a matrix. Collagen membranes varying in porosity, crosslinking density, structure and crosslinker were fabricated. Collagen characterized by infrared spectroscopy and solution viscosity was determined to be pure and native. The collagen membranes were determined to possess native vs. non-native quaternary structure and porous vs. dense aggregate membranes by electron microscopy. Collagen monolithic devices containing a model macromolecule (inulin) were fabricated. In vitro release rates were found to be linear with respect to t 1/2 and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and 14 C-inulin release rates were evaluated subcutaneously in rats

  7. Macromolecular crystallography research at Trombay

    International Nuclear Information System (INIS)

    Kannan, K.K.; Chidamrabam, R.

    1983-01-01

    Neutron diffraction studies of hydrogen positions in small molecules of biological interest at Trombay have provided valuable information that has been used in protein and enzyme structure model-building and in developing hydrogen bond potential functions. The new R-5 reactor is expected to provide higher neutron fluxes and also make possible small-angle neutron scattering studies of large biomolecules and bio-aggregates. In the last few years infrastructure facilities have also been established for macromolecular x-ray crystallography research. Meanwhile, the refinement of carbonic hydrases and lyysozyme structures have been carried out and interesting results obtained on protein dynamics and structure-function relationships. Some interesting presynaptic toxin phospholipases have also taken up for study. (author)

  8. Design and application of a C++ macromolecular class library.

    Science.gov (United States)

    Chang, W; Shindyalov, I N; Pu, C; Bourne, P E

    1994-01-01

    PDBlib is an extensible object oriented class library written in C++ for representing the 3-dimensional structure of biological macromolecules. PDBlib forms the kernel of a larger software framework being developed for assiting in knowledge discovery from macromolecular structure data. The software design strategy used by PDBlib, how the library may be used and several prototype applications that use the library are summarized. PDBlib represents the structural features of proteins, DNA, RNA, and complexes thereof, at a level of detail on a par with that which can be parsed from a Protein Data Bank (PDB) entry. However, the memory resident representation of the macromolecule is independent of the PDB entry and can be obtained from other back-end data sources, for example, existing relational databases and our own object oriented database (OOPDB) built on top of the commercial object oriented database, ObjectStore. At the front-end are several prototype applications that use the library: Macromolecular Query Language (MMQL) is based on a separate class library (MMQLlib) for building complex queries pertaining to macromolecular structure; PDBtool is an interactive structure verification tool; and PDBview, is a structure rendering tool used either as a standalone tool or as part of another application. Each of these software components are described. All software is available via anonymous ftp from cuhhca.hhmi.columbia.edu.

  9. Stochastic reaction-diffusion algorithms for macromolecular crowding

    Science.gov (United States)

    Sturrock, Marc

    2016-06-01

    Compartment-based (lattice-based) reaction-diffusion algorithms are often used for studying complex stochastic spatio-temporal processes inside cells. In this paper the influence of macromolecular crowding on stochastic reaction-diffusion simulations is investigated. Reaction-diffusion processes are considered on two different kinds of compartmental lattice, a cubic lattice and a hexagonal close packed lattice, and solved using two different algorithms, the stochastic simulation algorithm and the spatiocyte algorithm (Arjunan and Tomita 2010 Syst. Synth. Biol. 4, 35-53). Obstacles (modelling macromolecular crowding) are shown to have substantial effects on the mean squared displacement and average number of molecules in the domain but the nature of these effects is dependent on the choice of lattice, with the cubic lattice being more susceptible to the effects of the obstacles. Finally, improvements for both algorithms are presented.

  10. Status and prospects of macromolecular crystallography

    Indian Academy of Sciences (India)

    technique that could be completely automated in most cases. ... major challenge in macromolecular crystallography today is ... tial characterization of crystals in the home source and make a ... opportunities for a generation of structural biolo-.

  11. Macromolecular synthesis in algal cells

    International Nuclear Information System (INIS)

    Ishida, M.R.; Kikuchi, Tadatoshi

    1980-01-01

    The present paper is a review of our experimental results obtained previously on the macromolecular biosyntheses in the cells of blue-green alga Anacystis nidulans as a representative species of prokaryote, and also in those of three species of eukaryotic algae, i.e. Euglena gracilis strain Z, Chlamydomonas reinhardi, and Cyanidium caldarium. In these algal cells, the combined methods consisting of pulse-labelling using 32 P, 3 H- and 14 C-labelled precursors for macromolecules, of their chasing and of the use of inhibitors which block specifically the syntheses of macromolecules such as proteins, RNA and DNA in living cells were very effectively applied for the analyses of the regulatory mechanism in biosyntheses of macromolecules and of the mode of their assembly into the cell structure, especially organelle constituents. Rased on the results obtained thus, the following conclusions are reached: (1) the metabolic pool for syntheses of macromolecules in the cells of prokaryotic blue-green alga is limited to the small extent and such activities couple largely with the photosynthetic mechanism; (2) 70 S ribosomes in the blue-green algal cells are assembled on the surface of thylakoid membranes widely distributed in their cytoplasm; and (3) the cells of eukaryotic unicellular algae used here have biochemical characters specific for already differentiated enzyme system involving in transcription and translation machineries as the same as in higher organisms, but the control mechanism concerning with such macromolecule syntheses are different among each species. (author)

  12. The design of macromolecular crystallography diffraction experiments

    International Nuclear Information System (INIS)

    Evans, Gwyndaf; Axford, Danny; Owen, Robin L.

    2011-01-01

    Thoughts about the decisions made in designing macromolecular X-ray crystallography experiments at synchrotron beamlines are presented. The measurement of X-ray diffraction data from macromolecular crystals for the purpose of structure determination is the convergence of two processes: the preparation of diffraction-quality crystal samples on the one hand and the construction and optimization of an X-ray beamline and end station on the other. Like sample preparation, a macromolecular crystallography beamline is geared to obtaining the best possible diffraction measurements from crystals provided by the synchrotron user. This paper describes the thoughts behind an experiment that fully exploits both the sample and the beamline and how these map into everyday decisions that users can and should make when visiting a beamline with their most precious crystals

  13. Exploration of inclusion complexes of neurotransmitters with β-cyclodextrin by physicochemical techniques

    Science.gov (United States)

    Roy, Mahendra Nath; Saha, Subhadeep; Kundu, Mitali; Saha, Binoy Chandra; Barman, Siti

    2016-07-01

    Molecular assemblies of β-cyclodextrin with few of the most important neurotransmitters, viz., dopamine hydrochloride, tyramine hydrochloride and (±)-epinephrine hydrochloride in aqueous medium have been explored by reliable spectroscopic and physicochemical techniques as potential drug delivery systems. Job plots confirm the 1:1 host-guest inclusion complexes, while surface tension and conductivity studies illustrate the inclusion process. The inclusion complexes were characterized by 1H NMR spectroscopy and association constants have been calculated by using Benesi-Hildebrand method. Thermodynamic parameters for the formation of inclusion complexes have been derived by van't Hoff equation, which demonstrate that the overall inclusion processes are thermodynamically favorable.

  14. Automated data collection for macromolecular crystallography.

    Science.gov (United States)

    Winter, Graeme; McAuley, Katherine E

    2011-09-01

    An overview, together with some practical advice, is presented of the current status of the automation of macromolecular crystallography (MX) data collection, with a focus on MX beamlines at Diamond Light Source, UK. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Host-guest interaction on Bruny and Magnetic Islands, Australia

    OpenAIRE

    Moyle, Brent Don

    2017-01-01

    Islands are integral to the earth’s biodiversity, with their distinct environments offering a haven for a variety of threatened species of plants, wildlife and unique human cultures. Worldwide, tourism activity profoundly impacts upon destinations, but the impacts on islands are noticeably more acute due to their fragile environments and isolated communities. Research has found that tourism can impact island communities in a variety of ways, including economically, socially and environmentall...

  16. Reversible Guest Exchange Mechanisms in Supramolecular Host-GuestAssemblies

    Energy Technology Data Exchange (ETDEWEB)

    Pluth, Michael D.; Raymond, Kenneth N.

    2006-09-01

    Synthetic chemists have provided a wide array of supramolecular assemblies able to encapsulate guest molecules. The scope of this tutorial review focuses on supramolecular host molecules capable of reversibly encapsulating polyatomic guests. Much work has been done to determine the mechanism of guest encapsulation and guest release. This review covers common methods of monitoring and characterizing guest exchange such as NMR, UV-VIS, mass spectroscopy, electrochemistry, and calorimetry and also presents representative examples of guest exchange mechanisms. The guest exchange mechanisms of hemicarcerands, cucurbiturils, hydrogen-bonded assemblies, and metal-ligand assemblies are discussed. Special attention is given to systems which exhibit constrictive binding, a motif common in supramolecular guest exchange systems.

  17. Host-guest supramolecular nanosystems for cancer diagnostics and therapeutics.

    Science.gov (United States)

    Wang, Lei; Li, Li-li; Fan, Yun-shan; Wang, Hao

    2013-07-26

    Extensive efforts have been devoted to the construction of functional supramolecular nanosystems for applications in catalysis, energy conversion, sensing and biomedicine. The applications of supramolecular nanosystems such as liposomes, micelles, inorganic nanoparticles, carbon materials for cancer diagnostics and therapeutics have been reviewed by other groups. Here, we will focus on the recent momentous advances in the implementation of typical supramolecular hosts (i.e., cyclodextrins, calixarenes, cucurbiturils and metallo-hosts) and their nanosystems in cancer diagnostics and therapeutics. We discuss the evolutive process of supramolecular nanosystems from the structural control and characterization to their diagnostic and therapeutic function exploitation and even the future potentials for clinical translation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. The Joint Structural Biology Group beam lines at the ESRF: Modern macromolecular crystallography

    CERN Document Server

    Mitchell, E P

    2001-01-01

    Macromolecular crystallography has evolved considerably over the last decade. Data sets in under an hour are now possible on high throughput beam lines leading to electron density and, possibly, initial models calculated on-site. There are five beam lines currently dedicated to macromolecular crystallography: the ID14 complex and BM-14 (soon to be superseded by ID-29). These lines handle over five hundred projects every six months and demand is increasing. Automated sample handling, alignment and data management protocols will be required to work efficiently with this demanding load. Projects developing these themes are underway within the JSBG.

  19. Oxidation of aromatic alcohols on zeolite-encapsulated copper amino acid complexes

    Energy Technology Data Exchange (ETDEWEB)

    Ernst, S.; Teixeira Florencio, J.M. [Kaiserslautern Univ. (Germany). Dept. of Chemistry, Chemical Technology

    1998-12-31

    Copper complexes of the amino acids histidine, arginine and lysine have been introduced into the supercages of zeolite Y and, for the first time, into the large intracrystalline cavities of zeolites EMT and MCM-22. The resulting host/guest compounds are characterized by X-ray powder diffraction, UV/VIS-spectroscopy in the diffuse reflectance mode and by catalytic tests in the liquid-phase oxidation of aromatic alcohols (viz. benzyl alcohol, 2- and 3-methylbenzyl alcohol and 2,5-dimethylbenzyl alcohol) with tertiary-butylhydroperoxide as oxidant. It was observed that intracrystalline copper-amino acid complexes possess remarkable catalytic activity, yielding the corresponding aromatic aldehydes and acids. (orig.)

  20. Topology evolution in macromolecular networks

    NARCIS (Netherlands)

    Kryven, I.

    2014-01-01

    Governed by various intermolecular forces, molecular networks tend to evolve from simple to very complex formations that have random structure. This randomness in the connectivity of the basic units can still be captured employing distributional description of the state of the system; the evolution

  1. Macromolecular Networks Containing Fluorinated Cyclic Moieties

    Science.gov (United States)

    2015-12-12

    Briefing Charts 3. DATES COVERED (From - To) 17 Nov 2015 – 12 Dec 2015 4. TITLE AND SUBTITLE Macromolecular Networks Containing Fluorinated Cyclic... FLUORINATED CYCLIC MOIETIES 12 December 2015 Andrew J. Guenthner,1 Scott T. Iacono,2 Cynthia A. Corley,2 Christopher M. Sahagun,3 Kevin R. Lamison,4...Reinforcements Good Flame, Smoke, & Toxicity Characteristics Low Water Uptake with Near Zero Coefficient of Hygroscopic Expansion ∆ DISTRIBUTION A

  2. A primer in macromolecular linguistics.

    Science.gov (United States)

    Searls, David B

    2013-03-01

    Polymeric macromolecules, when viewed abstractly as strings of symbols, can be treated in terms of formal language theory, providing a mathematical foundation for characterizing such strings both as collections and in terms of their individual structures. In addition this approach offers a framework for analysis of macromolecules by tools and conventions widely used in computational linguistics. This article introduces the ways that linguistics can be and has been applied to molecular biology, covering the relevant formal language theory at a relatively nontechnical level. Analogies between macromolecules and human natural language are used to provide intuitive insights into the relevance of grammars, parsing, and analysis of language complexity to biology. Copyright © 2012 Wiley Periodicals, Inc.

  3. Distributed computing for macromolecular crystallography.

    Science.gov (United States)

    Krissinel, Evgeny; Uski, Ville; Lebedev, Andrey; Winn, Martyn; Ballard, Charles

    2018-02-01

    Modern crystallographic computing is characterized by the growing role of automated structure-solution pipelines, which represent complex expert systems utilizing a number of program components, decision makers and databases. They also require considerable computational resources and regular database maintenance, which is increasingly more difficult to provide at the level of individual desktop-based CCP4 setups. On the other hand, there is a significant growth in data processed in the field, which brings up the issue of centralized facilities for keeping both the data collected and structure-solution projects. The paradigm of distributed computing and data management offers a convenient approach to tackling these problems, which has become more attractive in recent years owing to the popularity of mobile devices such as tablets and ultra-portable laptops. In this article, an overview is given of developments by CCP4 aimed at bringing distributed crystallographic computations to a wide crystallographic community.

  4. Macromolecular nanotheranostics for multimodal anticancer therapy

    Science.gov (United States)

    Huis in't Veld, Ruben; Storm, Gert; Hennink, Wim E.; Kiessling, Fabian; Lammers, Twan

    2011-10-01

    Macromolecular carrier materials based on N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well-characterized drug delivery systems that have been extensively evaluated in the past two decades, both at the preclinical and at the clinical level. Using several different imaging agents and techniques, HPMA copolymers have been shown to circulate for prolonged periods of time, and to accumulate in tumors both effectively and selectively by means of the Enhanced Permeability and Retention (EPR) effect. Because of this, HPMA-based macromolecular nanotheranostics, i.e. formulations containing both drug and imaging agents within a single formulation, have been shown to be highly effective in inducing tumor growth inhibition in animal models. In patients, however, as essentially all other tumor-targeted nanomedicines, they are generally only able to improve the therapeutic index of the attached active agent by lowering its toxicity, and they fail to improve the efficacy of the intervention. Bearing this in mind, we have recently reasoned that because of their biocompatibility and their beneficial biodistribution, nanomedicine formulations might be highly suitable systems for combination therapies. In the present manuscript, we briefly summarize several exemplary efforts undertaken in this regard in our labs in the past couple of years, and we show that long-circulating and passively tumor-targeted macromolecular nanotheranostics can be used to improve the efficacy of radiochemotherapy and of chemotherapy combinations.

  5. Exploring inclusion complexes of ionic liquids with α- and β- cyclodextrin by NMR, IR, mass, density, viscosity, surface tension and conductance study

    Science.gov (United States)

    Barman, Biraj Kumar; Rajbanshi, Biplab; Yasmin, Ananya; Roy, Mahendra Nath

    2018-05-01

    The formation of the host-guest inclusion complexes of ionic liquids namely [BMIm]Cl and [HMIm]Cl with α-CD and β-CD were studied by means of physicochemical and spectroscopic methods. Conductivity and surface tension study were in good agreement with the 1H NMR and FT-IR studies which confirm the formation of the inclusion complexes. The Density and viscosity study also supported the formation of the ICs. Further the stoichiometry was determined 1:1 for each case and the association constants and thermodynamic parameters derived supported the most feasible formation of the [BMIm]Cl- β-CD inclusion complex.

  6. THESEUS: maximum likelihood superpositioning and analysis of macromolecular structures.

    Science.gov (United States)

    Theobald, Douglas L; Wuttke, Deborah S

    2006-09-01

    THESEUS is a command line program for performing maximum likelihood (ML) superpositions and analysis of macromolecular structures. While conventional superpositioning methods use ordinary least-squares (LS) as the optimization criterion, ML superpositions provide substantially improved accuracy by down-weighting variable structural regions and by correcting for correlations among atoms. ML superpositioning is robust and insensitive to the specific atoms included in the analysis, and thus it does not require subjective pruning of selected variable atomic coordinates. Output includes both likelihood-based and frequentist statistics for accurate evaluation of the adequacy of a superposition and for reliable analysis of structural similarities and differences. THESEUS performs principal components analysis for analyzing the complex correlations found among atoms within a structural ensemble. ANSI C source code and selected binaries for various computing platforms are available under the GNU open source license from http://monkshood.colorado.edu/theseus/ or http://www.theseus3d.org.

  7. Extracting trends from two decades of microgravity macromolecular crystallization history.

    Science.gov (United States)

    Judge, Russell A; Snell, Edward H; van der Woerd, Mark J

    2005-06-01

    Since the 1980s hundreds of macromolecular crystal growth experiments have been performed in the reduced acceleration environment of an orbiting spacecraft. Significant enhancements in structural knowledge have resulted from X-ray diffraction of the crystals grown. Similarly, many samples have shown no improvement or degradation in comparison to those grown on the ground. A complex series of interrelated factors affect these experiments and by building a comprehensive archive of the results it was aimed to identify factors that result in success and those that result in failure. Specifically, it was found that dedicated microgravity missions increase the chance of success when compared with those where crystallization took place as a parasitic aspect of the mission. It was also found that the chance of success could not be predicted based on any discernible property of the macromolecule available to us.

  8. Macromolecular organization of xyloglucan and cellulose in pea epicotyls

    International Nuclear Information System (INIS)

    Hayashi, T.; Maclachlan, G.

    1984-01-01

    Xyloglucan is known to occur widely in the primary cell walls of higher plants. This polysaccharide in most dicots possesses a cellulose-like main chain with three of every four consecutive residues substituted with xylose and minor addition of other sugars. Xyloglucan and cellulose metabolism is regulated by different processes; since different enzyme systems are probably required for the synthesis of their 1,4-β-linkages. A macromolecular complex composed of xyloglucan and cellulose only was obtained from elongating regions of etiolated pea stems. It was examined by light microscopy using iodine staining, by radioautography after labeling with [ 3 H]fructose, by fluorescence microscopy using a fluorescein-lectin (fructose-binding) as probe, and by electron microscopy after shadowing. The techniques all demonstrated that the macromolecule was present in files of cell shapes, referred to here as cell-wall ghosts, in which xyloglucan was localized both on and between the cellulose microfibrils

  9. Local analysis of strains and rotations for macromolecular electron microscopy maps

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Ramos, A.; Prieto, F.; Melero, R.; Martin-Benito, J.; Jonic, S.; Navas-Calvente, J.; Vargas, J.; Oton, J.; Abrishami, V.; Rosa-Trevin, J.L. de la; Gomez-Blanco, J.; Vilas, J.L.; Marabini, R.; Carazo, R.; Sorzano, C.O.S.

    2016-07-01

    Macromolecular complexes can be considered as molecular nano-machines that must have mobile parts in order to perform their physiological functions. The reordering of their parts is essential to execute their task. These rearrangements induce local strains and rotations which, after analyzing them, may provide relevant information about how the proteins perform their function. In this project these deformations of the macromolecular complexes are characterized, translating into a “mathematical language” the conformational changes of the complexes when they perform their function. Electron Microscopy (EM) volumes are analyzed using a method that uses B-splines as its basis functions. It is shown that the results obtained are consistent with the conformational changes described in their corresponding reference publications. (Author)

  10. A public database of macromolecular diffraction experiments.

    Science.gov (United States)

    Grabowski, Marek; Langner, Karol M; Cymborowski, Marcin; Porebski, Przemyslaw J; Sroka, Piotr; Zheng, Heping; Cooper, David R; Zimmerman, Matthew D; Elsliger, Marc André; Burley, Stephen K; Minor, Wladek

    2016-11-01

    The low reproducibility of published experimental results in many scientific disciplines has recently garnered negative attention in scientific journals and the general media. Public transparency, including the availability of `raw' experimental data, will help to address growing concerns regarding scientific integrity. Macromolecular X-ray crystallography has led the way in requiring the public dissemination of atomic coordinates and a wealth of experimental data, making the field one of the most reproducible in the biological sciences. However, there remains no mandate for public disclosure of the original diffraction data. The Integrated Resource for Reproducibility in Macromolecular Crystallography (IRRMC) has been developed to archive raw data from diffraction experiments and, equally importantly, to provide related metadata. Currently, the database of our resource contains data from 2920 macromolecular diffraction experiments (5767 data sets), accounting for around 3% of all depositions in the Protein Data Bank (PDB), with their corresponding partially curated metadata. IRRMC utilizes distributed storage implemented using a federated architecture of many independent storage servers, which provides both scalability and sustainability. The resource, which is accessible via the web portal at http://www.proteindiffraction.org, can be searched using various criteria. All data are available for unrestricted access and download. The resource serves as a proof of concept and demonstrates the feasibility of archiving raw diffraction data and associated metadata from X-ray crystallographic studies of biological macromolecules. The goal is to expand this resource and include data sets that failed to yield X-ray structures in order to facilitate collaborative efforts that will improve protein structure-determination methods and to ensure the availability of `orphan' data left behind for various reasons by individual investigators and/or extinct structural genomics

  11. Celebrating macromolecular crystallography: A personal perspective

    Directory of Open Access Journals (Sweden)

    Abad-Zapatero, Celerino

    2015-04-01

    Full Text Available The twentieth century has seen an enormous advance in the knowledge of the atomic structures that surround us. The discovery of the first crystal structures of simple inorganic salts by the Braggs in 1914, using the diffraction of X-rays by crystals, provided the critical elements to unveil the atomic structure of matter. Subsequent developments in the field leading to macromolecular crystallography are presented with a personal perspective, related to the cultural milieu of Spain in the late 1950’s. The journey of discovery of the author, as he developed professionally, is interwoven with the expansion of macromolecular crystallography from the first proteins (myoglobin, hemoglobin to the ‘coming of age’ of the field in 1971 and the discoveries that followed, culminating in the determination of the structure of the ribosomes at the turn of the century. A perspective is presented exploring the future of the field and also a reflection about the future generations of Spanish scientists.El siglo XX ha sido testigo del increíble avance que ha experimentado el conocimiento de la estructura atómica de la materia que nos rodea. El descubrimiento de las primeras estructuras atómicas de sales inorgánicas por los Bragg en 1914, empleando difracción de rayos X con cristales, proporcionó los elementos clave para alcanzar tal conocimiento. Posteriores desarrollos en este campo, que condujeron a la cristalografía macromolecular, se presentan aquí desde una perspectiva personal, relacionada con el contexto cultural de la España de la década de los 50. La experiencia del descubrimiento científico, durante mi desarrollo profesional, se integra en el desarrollo de la cristalografía macromolecular, desde las primeras proteínas (míoglobina y hemoglobina, hasta su madurez en 1971 que, con los posteriores descubrimientos, culmina con la determinación del la estructura del ribosoma. Asimismo, se explora el futuro de esta disciplina y se

  12. MMTF-An efficient file format for the transmission, visualization, and analysis of macromolecular structures.

    Directory of Open Access Journals (Sweden)

    Anthony R Bradley

    2017-06-01

    Full Text Available Recent advances in experimental techniques have led to a rapid growth in complexity, size, and number of macromolecular structures that are made available through the Protein Data Bank. This creates a challenge for macromolecular visualization and analysis. Macromolecular structure files, such as PDB or PDBx/mmCIF files can be slow to transfer, parse, and hard to incorporate into third-party software tools. Here, we present a new binary and compressed data representation, the MacroMolecular Transmission Format, MMTF, as well as software implementations in several languages that have been developed around it, which address these issues. We describe the new format and its APIs and demonstrate that it is several times faster to parse, and about a quarter of the file size of the current standard format, PDBx/mmCIF. As a consequence of the new data representation, it is now possible to visualize structures with millions of atoms in a web browser, keep the whole PDB archive in memory or parse it within few minutes on average computers, which opens up a new way of thinking how to design and implement efficient algorithms in structural bioinformatics. The PDB archive is available in MMTF file format through web services and data that are updated on a weekly basis.

  13. Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy.

    Science.gov (United States)

    Loquet, Antoine; Tolchard, James; Berbon, Melanie; Martinez, Denis; Habenstein, Birgit

    2017-09-17

    Supramolecular protein assemblies play fundamental roles in biological processes ranging from host-pathogen interaction, viral infection to the propagation of neurodegenerative disorders. Such assemblies consist in multiple protein subunits organized in a non-covalent way to form large macromolecular objects that can execute a variety of cellular functions or cause detrimental consequences. Atomic insights into the assembly mechanisms and the functioning of those macromolecular assemblies remain often scarce since their inherent insolubility and non-crystallinity often drastically reduces the quality of the data obtained from most techniques used in structural biology, such as X-ray crystallography and solution Nuclear Magnetic Resonance (NMR). We here present magic-angle spinning solid-state NMR spectroscopy (SSNMR) as a powerful method to investigate structures of macromolecular assemblies at atomic resolution. SSNMR can reveal atomic details on the assembled complex without size and solubility limitations. The protocol presented here describes the essential steps from the production of 13 C/ 15 N isotope-labeled macromolecular protein assemblies to the acquisition of standard SSNMR spectra and their analysis and interpretation. As an example, we show the pipeline of a SSNMR structural analysis of a filamentous protein assembly.

  14. Probing the hydration water diffusion of macromolecular surfaces and interfaces

    International Nuclear Information System (INIS)

    Ortony, Julia H; Cheng, Chi-Yuan; Franck, John M; Pavlova, Anna; Hunt, Jasmine; Han, Songi; Kausik, Ravinath

    2011-01-01

    We probe the translational dynamics of the hydration water surrounding the macromolecular surfaces of selected polyelectrolytes, lipid vesicles and intrinsically disordered proteins with site specificity in aqueous solutions. These measurements are made possible by the recent development of a new instrumental and methodological approach based on Overhauser dynamic nuclear polarization (DNP)-enhanced nuclear magnetic resonance (NMR) spectroscopy. This technique selectively amplifies 1 H NMR signals of hydration water around a spin label that is attached to a molecular site of interest. The selective 1 H NMR amplification within molecular length scales of a spin label is achieved by utilizing short-distance range (∼r -3 ) magnetic dipolar interactions between the 1 H spin of water and the electron spin of a nitroxide radical-based label. Key features include the fact that only minute quantities (<10 μl) and dilute (≥100 μM) sample concentrations are needed. There is no size limit on the macromolecule or molecular assembly to be analyzed. Hydration water with translational correlation times between 10 and 800 ps is measured within ∼10 A distance of the spin label, encompassing the typical thickness of a hydration layer with three water molecules across. The hydration water moving within this time scale has significant implications, as this is what is modulated whenever macromolecules or molecular assemblies undergo interactions, binding or conformational changes. We demonstrate, with the examples of polymer complexation, protein aggregation and lipid-polymer interaction, that the measurements of interfacial hydration dynamics can sensitively and site specifically probe macromolecular interactions.

  15. The role of macromolecular stability in desiccation tolerance

    NARCIS (Netherlands)

    Wolkers, W.F.

    1998-01-01

    The work presented in this thesis concerns a study on the molecular interactions that play a role in the macromolecular stability of desiccation-tolerant higher plant organs. Fourier transform infrared microspectroscopy was used as the main experimental technique to assess macromolecular

  16. Generalized Born Models of Macromolecular Solvation Effects

    Science.gov (United States)

    Bashford, Donald; Case, David A.

    2000-10-01

    It would often be useful in computer simulations to use a simple description of solvation effects, instead of explicitly representing the individual solvent molecules. Continuum dielectric models often work well in describing the thermodynamic aspects of aqueous solvation, and approximations to such models that avoid the need to solve the Poisson equation are attractive because of their computational efficiency. Here we give an overview of one such approximation, the generalized Born model, which is simple and fast enough to be used for molecular dynamics simulations of proteins and nucleic acids. We discuss its strengths and weaknesses, both for its fidelity to the underlying continuum model and for its ability to replace explicit consideration of solvent molecules in macromolecular simulations. We focus particularly on versions of the generalized Born model that have a pair-wise analytical form, and therefore fit most naturally into conventional molecular mechanics calculations.

  17. [Macromolecular aromatic network characteristics of Chinese power coal analyzed by synchronous fluorescence and X-ray diffraction].

    Science.gov (United States)

    Ye, Cui-Ping; Feng, Jie; Li, Wen-Ying

    2012-07-01

    Coal structure, especially the macromolecular aromatic skeleton structure, has a strong influence on coke reactivity and coal gasification, so it is the key to grasp the macromolecular aromatic skeleton coal structure for getting the reasonable high efficiency utilization of coal. However, it is difficult to acquire their information due to the complex compositions and structure of coal. It has been found that the macromolecular aromatic network coal structure would be most isolated if small molecular of coal was first extracted. Then the macromolecular aromatic skeleton coal structure would be clearly analyzed by instruments, such as X-ray diffraction (XRD), fluorescence spectroscopy with synchronous mode (Syn-F), Gel permeation chromatography (GPC) etc. Based on the previous results, according to the stepwise fractional liquid extraction, two Chinese typical power coals, PS and HDG, were extracted by silica gel as stationary phase and acetonitrile, tetrahydrofuran (THF), pyridine and 1-methyl-2-pyrollidinone (NMP) as a solvent group for sequential elution. GPC, Syn-F and XRD were applied to investigate molecular mass distribution, condensed aromatic structure and crystal characteristics. The results showed that the size of aromatic layers (La) is small (3-3.95 nm) and the stacking heights (Lc) are 0.8-1.2 nm. The molecular mass distribution of the macromolecular aromatic network structure is between 400 and 1 130 amu, with condensed aromatic numbers of 3-7 in the structure units.

  18. Complexation of imidazopyridine-based cations with a 24-crown-8 ether host: [2]pseudorotaxane and partially threaded structures.

    Science.gov (United States)

    Moreno-Olivares, Surisadai I; Cervantes, Ruy; Tiburcio, Jorge

    2013-11-01

    A new series of linear molecules derived from 1,2-bis(imidazopyridin-2-yl)ethane can fully or partially penetrate the cavity of the dibenzo-24-crown-8 macrocycle to produce a new family of host-guest complexes. Protonation or alkylation of the nitrogen atoms on the pyridine rings led to an increase in the guest total positive charge up to 4+ and simultaneously generated two new recognition sites (pyridinium motifs) that are in competition with the 1,2-bis(benzimidazole)ethane motif for the crown ether. The relative position of the pyridine ring and the chemical nature of the N-substituent determined the preferred motif and the host-guest complex geometry: (i) for linear guests with relatively bulky groups (i.e., a benzyl substituent), the 1,2-bis(benzimidazole)ethane motif is favored, leading to a fully threaded complex with a [2]pseudorotaxane geometry; (ii) for small substituents, such as -H and -CH3 groups, regardless of the guest shape, the pyridinium motifs are preferred, leading to external partially threaded complexes in a 2:1 host to guest stoichiometry.

  19. Variationally optimal selection of slow coordinates and reaction coordinates in macromolecular systems

    Science.gov (United States)

    Noe, Frank

    To efficiently simulate and generate understanding from simulations of complex macromolecular systems, the concept of slow collective coordinates or reaction coordinates is of fundamental importance. Here we will introduce variational approaches to approximate the slow coordinates and the reaction coordinates between selected end-states given MD simulations of the macromolecular system and a (possibly large) basis set of candidate coordinates. We will then discuss how to select physically intuitive order paremeters that are good surrogates of this variationally optimal result. These result can be used in order to construct Markov state models or other models of the stationary and kinetics properties, in order to parametrize low-dimensional / coarse-grained model of the dynamics. Deutsche Forschungsgemeinschaft, European Research Council.

  20. Complex macromolecular architectures: synthesis, characterization, and self-assembly

    National Research Council Canada - National Science Library

    Hadjichristidis, Nikos

    2011-01-01

    ...)s and gluco-polymers, star-branched and dendrimer-like hyperbranched polymers, cyclic polymers, dendrigraft polymers, rod-coil and helix-coil block copolymers are introduced chapter by chapter in the book...

  1. Macromolecular peroxo complexes of Vanadium(V) and ...

    Indian Academy of Sciences (India)

    Molybdenum(VI): Catalytic activities and biochemical relevance. NASHREEN S ISLAM∗ and ... already been identified as an important pathway for the action of inorganic drugs and .... chain or network. Physical incorporation of metals or.

  2. Sequential recovery of macromolecular components of the nucleolus.

    Science.gov (United States)

    Bai, Baoyan; Laiho, Marikki

    2015-01-01

    The nucleolus is involved in a number of cellular processes of importance to cell physiology and pathology, including cell stress responses and malignancies. Studies of macromolecular composition of the nucleolus depend critically on the efficient extraction and accurate quantification of all macromolecular components (e.g., DNA, RNA, and protein). We have developed a TRIzol-based method that efficiently and simultaneously isolates these three macromolecular constituents from the same sample of purified nucleoli. The recovered and solubilized protein can be accurately quantified by the bicinchoninic acid assay and assessed by polyacrylamide gel electrophoresis or by mass spectrometry. We have successfully applied this approach to extract and quantify the responses of all three macromolecular components in nucleoli after drug treatments of HeLa cells, and conducted RNA-Seq analysis of the nucleolar RNA.

  3. Macromolecular Crystal Growth by Means of Microfluidics

    Science.gov (United States)

    vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    We have performed a feasibility study in which we show that chip-based, microfluidic (LabChip(TM)) technology is suitable for protein crystal growth. This technology allows for accurate and reliable dispensing and mixing of very small volumes while minimizing bubble formation in the crystallization mixture. The amount of (protein) solution remaining after completion of an experiment is minimal, which makes this technique efficient and attractive for use with proteins, which are difficult or expensive to obtain. The nature of LabChip(TM) technology renders it highly amenable to automation. Protein crystals obtained in our initial feasibility studies were of excellent quality as determined by X-ray diffraction. Subsequent to the feasibility study, we designed and produced the first LabChip(TM) device specifically for protein crystallization in batch mode. It can reliably dispense and mix from a range of solution constituents into two independent growth wells. We are currently testing this design to prove its efficacy for protein crystallization optimization experiments. In the near future we will expand our design to incorporate up to 10 growth wells per LabChip(TM) device. Upon completion, additional crystallization techniques such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility for the International Space Station as well as on the ground.

  4. Fluid Physics and Macromolecular Crystal Growth in Microgravity

    Science.gov (United States)

    Helliwell, John R.; Snell, Edward H.; Chayen, Naomi E.; Judge, Russell A.; Boggon, Titus J.; Pusey, M. L.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    " is often historically used to describe these microgravity experiments. This is somewhat inaccurate as the field involves the study of many varied biological molecules including viruses, proteins, DNA, RNA and complexes of those structures. For this reason we use the term macromolecular crystal growth. In this chapter we review a series of diagnostic microgravity crystal growth experiments carried out principally using the European Space Agency (ESA) Advanced Protein Crystallization Facility (APCF). We also review related research, both experimental and theoretical, on the aspects of microgravity fluid physics that affect microgravity protein crystal growth. Our experiments have revealed some surprises that were not initially expected. We discuss them here in the context of practical lessons learnt and how to maximize the limited microgravity opportunities available.

  5. Free radical homopolymerization of a vinylferrocene/cyclodextrin complex in water

    Directory of Open Access Journals (Sweden)

    Helmut Ritter

    2010-06-01

    Full Text Available We report the radical initiated homopolymerization of a soluble vinylferrocene cyclodextrin-complex in water. Uncomplexed vinylferrocene 1 and the corresponding homopolymer are hydrophobic and completely insoluble in water. Complexation of 1 with methyl-β-cyclodextrin 2 results in clearly water-soluble structures due to incorporation of the ferrocene moiety into the cyclodextrin cavity. After free radical polymerization of the water-soluble complexed monomer, corresponding to polyvinylferrocene (PVFc, the water-soluble polymer is obtained due to the host guest interactions. Those polymeric complexes are stable in water up to about 90 °C. Above this temperature the polymer precipitates due to decomplexation. The complex was investigated by 1H NMR spectrometry, dynamic light scattering (DLS, differential scanning calorimetry (DSC, and lower critical solution temperature (LCST measurements.

  6. Self-Healing and Thermo-Responsive Dual-Crosslinked Alginate Hydrogels based on Supramolecular Inclusion Complexes

    Science.gov (United States)

    Miao, Tianxin; Fenn, Spencer L.; Charron, Patrick N.; Oldinski, Rachael A.

    2015-01-01

    β-cyclodextrin (β-CD), with a lipophilic inner cavity and hydrophilic outer surface, interacts with a large variety of non-polar guest molecules to form non-covalent inclusion complexes. Conjugation of β-CD onto biomacromolecules can form physically-crosslinked hydrogel networks upon mixing with a guest molecule. Herein describes the development and characterization of self-healing, thermo-responsive hydrogels, based on host-guest inclusion complexes between alginate-graft-β-CD and Pluronic® F108 (poly(ethylene glycol)-b-poly(propylene glycol)-b-poly(ethylene glycol)). The mechanics, flow characteristics, and thermal response were contingent on the polymer concentrations, and the host-guest molar ratio. Transient and reversible physical crosslinking between host and guest polymers governed self-assembly, allowing flow under shear stress, and facilitating complete recovery of the material properties within a few seconds of unloading. The mechanical properties of the dual-crosslinked, multi-stimuli responsive hydrogels were tuned as high as 30 kPa at body temperature, and are advantageous for biomedical applications such as drug delivery and cell transplantation. PMID:26509214

  7. Macromolecular query language (MMQL): prototype data model and implementation.

    Science.gov (United States)

    Shindyalov, I N; Chang, W; Pu, C; Bourne, P E

    1994-11-01

    Macromolecular query language (MMQL) is an extensible interpretive language in which to pose questions concerning the experimental or derived features of the 3-D structure of biological macromolecules. MMQL portends to be intuitive with a simple syntax, so that from a user's perspective complex queries are easily written. A number of basic queries and a more complex query--determination of structures containing a five-strand Greek key motif--are presented to illustrate the strengths and weaknesses of the language. The predominant features of MMQL are a filter and pattern grammar which are combined to express a wide range of interesting biological queries. Filters permit the selection of object attributes, for example, compound name and resolution, whereas the patterns currently implemented query primary sequence, close contacts, hydrogen bonding, secondary structure, conformation and amino acid properties (volume, polarity, isoelectric point, hydrophobicity and different forms of exposure). MMQL queries are processed by MMQLlib; a C++ class library, to which new query methods and pattern types are easily added. The prototype implementation described uses PDBlib, another C(++)-based class library from representing the features of biological macromolecules at the level of detail parsable from a PDB file. Since PDBlib can represent data stored in relational and object-oriented databases, as well as PDB files, once these data are loaded they too can be queried by MMQL. Performance metrics are given for queries of PDB files for which all derived data are calculated at run time and compared to a preliminary version of OOPDB, a prototype object-oriented database with a schema based on a persistent version of PDBlib which offers more efficient data access and the potential to maintain derived information. MMQLlib, PDBlib and associated software are available via anonymous ftp from cuhhca.hhmi.columbia.edu.

  8. Ca{sup 2+} ion sensing by a piperidin-4-one derivative and the effect of β-cyclodextrin complexation on the sensing

    Energy Technology Data Exchange (ETDEWEB)

    Sumithra, M.; Sivaraj, R.; Selvan, G. Tamil; Selvakumar, P. Mosae; Enoch, Israel V.M.V., E-mail: drisraelenoch@gmail.com

    2017-05-15

    In this paper, we report the turn-on fluorescence based Ca{sup 2+} ion sensing by an anthracene piperidin-4-one derivative. The compound is obtained using a simple two step synthesis. The compound is characterized using NMR and mass spectral methods. The host-guest complex formation of the compound with β-cyclodextrin is prepared and characterized using fluorescence and 2D ROESY spectroscopy. The compound forms the inclusion complex with a 1:1 stoichiometry. The structure of the host-guest complex is proposed. The Ca{sup 2+} ion selectivity of the compound in its free form and cyclodextrin-bound forms are studied. In both the forms, the piperidin-4-one derivative senses Ca{sup 2+} and in the case of the cyclodextrin encapsulated form it shows a better competitive binding of Ca{sup 2+} in the presence of other metal ions. - Highlights: •An anthracene iminoderivative of 3-methyl-2,6-diphenylpiperidin-4-one is synthesized. •The anthracene moiety of the compound is encapsulated by β-Cyclodextrin. •The compound senses Ca{sup 2+} ion both in water and β-CD media. •β-CD molecule does not interrupt the Ca{sup 2+} ion binding.

  9. Preparation, characterization, and thermal stability of β-cyclodextrin/soybean lecithin inclusion complex.

    Science.gov (United States)

    Wang, Xinge; Luo, Zhigang; Xiao, Zhigang

    2014-01-30

    β-Cyclodextrin (β-CD), which is widely used to increase the stability, solubility, and bioavailability of guests, can form host-guest inclusion complexes with a wide variety of organic molecules. In this study the β-CD/soybean lecithin inclusion complex was prepared. The effect of reaction parameters such as reaction temperature, reaction time and the molar ratio of β-CD/soybean lecithin on inclusion ratio were studied. The inclusion ratio of the product prepared under the optimal conditions of β-CD/soybean lecithin molar ratio 2:1, reaction temperature 60°C reaction time 2h was 40.2%. The results of UV-vis, DSC, XRD and FT-IR spectrum indicated the formation of inclusion complex. The thermal stability experiment indicated that the thermal stability of soybean lecithin in inclusion complex was significantly improved compared with free soybean lecithin. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. The Thermodynamics of Anion Complexation to Nonpolar Pockets.

    Science.gov (United States)

    Sullivan, Matthew R; Yao, Wei; Tang, Du; Ashbaugh, Henry S; Gibb, Bruce C

    2018-02-08

    The interactions between nonpolar surfaces and polarizable anions lie in a gray area between the hydrophobic and Hofmeister effects. To assess the affinity of these interactions, NMR and ITC were used to probe the thermodynamics of eight anions binding to four different hosts whose pockets each consist primarily of hydrocarbon. Two classes of host were examined: cavitands and cyclodextrins. For all hosts, anion affinity was found to follow the Hofmeister series, with associations ranging from 1.6-5.7 kcal mol -1 . Despite the fact that cavitand hosts 1 and 2 possess intrinsic negative electrostatic fields, it was determined that these more enveloping hosts generally bound anions more strongly. The observation that the four hosts each possess specific anion affinities that cannot be readily explained by their structures, points to the importance of counter cations and the solvation of the "empty" hosts, free guests, and host-guest complexes, in defining the affinity.

  11. Macromolecular crystallography beamline X25 at the NSLS

    Energy Technology Data Exchange (ETDEWEB)

    Héroux, Annie; Allaire, Marc; Buono, Richard; Cowan, Matthew L.; Dvorak, Joseph; Flaks, Leon; LaMarra, Steven; Myers, Stuart F.; Orville, Allen M.; Robinson, Howard H.; Roessler, Christian G.; Schneider, Dieter K.; Shea-McCarthy, Grace; Skinner, John M.; Skinner, Michael; Soares, Alexei S.; Sweet, Robert M.; Berman, Lonny E., E-mail: berman@bnl.gov [Brookhaven National Laboratory, PO Box 5000, Upton, NY 11973-5000 (United States)

    2014-04-08

    A description of the upgraded beamline X25 at the NSLS, operated by the PXRR and the Photon Sciences Directorate serving the Macromolecular Crystallography community, is presented. Beamline X25 at the NSLS is one of the five beamlines dedicated to macromolecular crystallography operated by the Brookhaven National Laboratory Macromolecular Crystallography Research Resource group. This mini-gap insertion-device beamline has seen constant upgrades for the last seven years in order to achieve mini-beam capability down to 20 µm × 20 µm. All major components beginning with the radiation source, and continuing along the beamline and its experimental hutch, have changed to produce a state-of-the-art facility for the scientific community.

  12. Macromolecular crystallography beamline X25 at the NSLS

    International Nuclear Information System (INIS)

    Héroux, Annie; Allaire, Marc; Buono, Richard; Cowan, Matthew L.; Dvorak, Joseph; Flaks, Leon; LaMarra, Steven; Myers, Stuart F.; Orville, Allen M.; Robinson, Howard H.; Roessler, Christian G.; Schneider, Dieter K.; Shea-McCarthy, Grace; Skinner, John M.; Skinner, Michael; Soares, Alexei S.; Sweet, Robert M.; Berman, Lonny E.

    2014-01-01

    A description of the upgraded beamline X25 at the NSLS, operated by the PXRR and the Photon Sciences Directorate serving the Macromolecular Crystallography community, is presented. Beamline X25 at the NSLS is one of the five beamlines dedicated to macromolecular crystallography operated by the Brookhaven National Laboratory Macromolecular Crystallography Research Resource group. This mini-gap insertion-device beamline has seen constant upgrades for the last seven years in order to achieve mini-beam capability down to 20 µm × 20 µm. All major components beginning with the radiation source, and continuing along the beamline and its experimental hutch, have changed to produce a state-of-the-art facility for the scientific community

  13. NMR studies of inclusion complexes formed by (R)-α-lipoic acid with α-, β-, and γ-cyclodextrins

    International Nuclear Information System (INIS)

    Ikeda, Hiroshi; Ikuta, Naoko; Nakata, Daisuke; Ishida, Yoshiyuki; Terao, Keiji

    2015-01-01

    The structures of inclusion complexes of (R)-α-lipoic acid with α-, β-, and γ-cyclodextrin (CD) were constructed using restraints derived from ROESY spectra and MMFF94 molecular mechanics calculations. (R)-α-lipoic acid and α-CD generate a single stable inclusion complex, in which the 1,2-dithiolane ring of the (R)-α-lipoic acid is oriented toward the secondary hydroxy side of the α-CD. NMR data suggests that β-CD produces two kinds of inclusion complexes with α-lipoic acid. Finally, γ-CD yields 1:1 and 1:2 host/guest complexes with (R)-α-lipoic acid. The estimated structure of the 1:1 γ-CD inclusion complex has the 1,2-dithiolane ring oriented toward the primary hydroxy side of the γ-CD. (author)

  14. Analytical model for macromolecular partitioning during yeast cell division

    International Nuclear Information System (INIS)

    Kinkhabwala, Ali; Khmelinskii, Anton; Knop, Michael

    2014-01-01

    Asymmetric cell division, whereby a parent cell generates two sibling cells with unequal content and thereby distinct fates, is central to cell differentiation, organism development and ageing. Unequal partitioning of the macromolecular content of the parent cell — which includes proteins, DNA, RNA, large proteinaceous assemblies and organelles — can be achieved by both passive (e.g. diffusion, localized retention sites) and active (e.g. motor-driven transport) processes operating in the presence of external polarity cues, internal asymmetries, spontaneous symmetry breaking, or stochastic effects. However, the quantitative contribution of different processes to the partitioning of macromolecular content is difficult to evaluate. Here we developed an analytical model that allows rapid quantitative assessment of partitioning as a function of various parameters in the budding yeast Saccharomyces cerevisiae. This model exposes quantitative degeneracies among the physical parameters that govern macromolecular partitioning, and reveals regions of the solution space where diffusion is sufficient to drive asymmetric partitioning and regions where asymmetric partitioning can only be achieved through additional processes such as motor-driven transport. Application of the model to different macromolecular assemblies suggests that partitioning of protein aggregates and episomes, but not prions, is diffusion-limited in yeast, consistent with previous reports. In contrast to computationally intensive stochastic simulations of particular scenarios, our analytical model provides an efficient and comprehensive overview of partitioning as a function of global and macromolecule-specific parameters. Identification of quantitative degeneracies among these parameters highlights the importance of their careful measurement for a given macromolecular species in order to understand the dominant processes responsible for its observed partitioning

  15. Modified gum Arabic hydrogels as matrices for controlled release of curcumin supramolecular complexes

    International Nuclear Information System (INIS)

    Gerola, Adriana P.; Silva, Danielle C.; Rubira, Adley F.; Muniz, Edvani C.

    2015-01-01

    Modified gum Arabic (GA) hydrogels show a pH-responsive behavior making them excellent matrices to be used for oral administration of drugs. Our goal is to study the behavior of those matrices in simulated gastric and intestinal fluids. In this work we will present how the methacrylation degree of GA, by using glycidyl methacrylate, can affect the properties of these hydrogels for controlled release. The drug used in this work is the curcumin (Cur). Cur is associated with numerous pharmacological activities, but their application is limited by the low water solubility. We will present some studies involving the formation of host-guest complexes between Cur and natural cyclodextrins. Both modified GA and hydrogels were characterized by different techniques. The kinetics release of Cur complex-containing modified GA hydrogels was studied to have an insight on the release mechanism and rate constants. Toxicity studies on undifferentiated and differentiated Caco-2 were also carried out. (author)

  16. Supra-molecular inclusion complexation of ionic liquid 1-butyl-3-methylimidazolium octylsulphate with α- and β-cyclodextrins

    Science.gov (United States)

    Banjare, Manoj Kumar; Behera, Kamalakanta; Satnami, Manmohan L.; Pandey, Siddharth; Ghosh, Kallol K.

    2017-12-01

    Host-guest complexation between ionic liquid (IL) 1-butyl-3-methylimidazolium octylsulphate [Bmim][OS] and cyclodextrins (α- and β- CDs) have been studied. Surface tension, conductivity measurements revealed the formation of 1:1 (M) stoichiometry for inclusion complexes (ICs) and further confirmed by UV-Visible and FT-IR results. The nature of the complexes has been established using interfacial and thermodynamic parameters. The aggregation number, Stern-Volmer constants, association constants were obtained from fluorescence quenching and Benesi-Hildebrand methods. The critical micelle concentration (cmc) and association constants of [Bmim][OS] are higher for β-CD as compared to α-CD. FT-IR spectra indicated that CDs and [Bmim][OS] could from ICs with stoichiometry 1:1 (M).

  17. A new paradigm for macromolecular crystallography beamlines derived from high-pressure methodology and results

    Energy Technology Data Exchange (ETDEWEB)

    Fourme, Roger, E-mail: roger.fourme@synchrotron-soleil.fr [Synchrotron SOLEIL, BP 48, Saint Aubin, 91192 Gif-sur-Yvette (France); Girard, Eric [IBS (UMR 5075 CEA-CNRS-UJF-PSB), 41 rue Jules Horowitz, 38027 Grenoble Cedex (France); Dhaussy, Anne-Claire [CRISMAT, ENSICAEN, 6 Boulevard du Maréchal Juin, 14000 Caen (France); Medjoubi, Kadda [Synchrotron SOLEIL, BP 48, Saint Aubin, 91192 Gif-sur-Yvette (France); Prangé, Thierry [LCRB (UMR 8015 CNRS), Université Paris Descartes, Faculté de Pharmacie, 4 avenue de l’Observatoire, 75270 Paris (France); Ascone, Isabella [ENSCP (UMR CNRS 7223), 11 rue Pierre et Marie Curie, 75231 Paris Cedex 05 (France); Mezouar, Mohamed [ESRF, BP 220, 38043 Grenoble (France); Kahn, Richard [IBS (UMR 5075 CEA-CNRS-UJF-PSB), 41 rue Jules Horowitz, 38027 Grenoble Cedex (France)

    2011-01-01

    Macromolecular crystallography at high pressure (HPMX) is a mature technique. Shorter X-ray wavelengths increase data collection efficiency on cryocooled crystals. Extending applications and exploiting spin-off of HPMX will require dedicated synchrotron radiation beamlines based on a new paradigm. Biological structures can now be investigated at high resolution by high-pressure X-ray macromolecular crystallography (HPMX). The number of HPMX studies is growing, with applications to polynucleotides, monomeric and multimeric proteins, complex assemblies and even a virus capsid. Investigations of the effects of pressure perturbation have encompassed elastic compression of the native state, study of proteins from extremophiles and trapping of higher-energy conformers that are often of biological interest; measurements of the compressibility of crystals and macromolecules were also performed. HPMX results were an incentive to investigate short and ultra-short wavelengths for standard biocrystallography. On cryocooled lysozyme crystals it was found that the data collection efficiency using 33 keV photons is increased with respect to 18 keV photons. This conclusion was extended from 33 keV down to 6.5 keV by exploiting previously published data. To be fully exploited, the potential of higher-energy photons requires detectors with a good efficiency. Accordingly, a new paradigm for MX beamlines was suggested, using conventional short and ultra-short wavelengths, aiming at the collection of very high accuracy data on crystals under standard conditions or under high pressure. The main elements of such beamlines are outlined.

  18. Crowding-facilitated macromolecular transport in attractive micropost arrays.

    Science.gov (United States)

    Chien, Fan-Tso; Lin, Po-Keng; Chien, Wei; Hung, Cheng-Hsiang; Yu, Ming-Hung; Chou, Chia-Fu; Chen, Yeng-Long

    2017-05-02

    Our study of DNA dynamics in weakly attractive nanofabricated post arrays revealed crowding enhances polymer transport, contrary to hindered transport in repulsive medium. The coupling of DNA diffusion and adsorption to the microposts results in more frequent cross-post hopping and increased long-term diffusivity with increased crowding density. We performed Langevin dynamics simulations and found maximum long-term diffusivity in post arrays with gap sizes comparable to the polymer radius of gyration. We found that macromolecular transport in weakly attractive post arrays is faster than in non-attractive dense medium. Furthermore, we employed hidden Markov analysis to determine the transition of macromolecular adsorption-desorption on posts and hopping between posts. The apparent free energy barriers are comparable to theoretical estimates determined from polymer conformational fluctuations.

  19. Diffusion accessibility as a method for visualizing macromolecular surface geometry.

    Science.gov (United States)

    Tsai, Yingssu; Holton, Thomas; Yeates, Todd O

    2015-10-01

    Important three-dimensional spatial features such as depth and surface concavity can be difficult to convey clearly in the context of two-dimensional images. In the area of macromolecular visualization, the computer graphics technique of ray-tracing can be helpful, but further techniques for emphasizing surface concavity can give clearer perceptions of depth. The notion of diffusion accessibility is well-suited for emphasizing such features of macromolecular surfaces, but a method for calculating diffusion accessibility has not been made widely available. Here we make available a web-based platform that performs the necessary calculation by solving the Laplace equation for steady state diffusion, and produces scripts for visualization that emphasize surface depth by coloring according to diffusion accessibility. The URL is http://services.mbi.ucla.edu/DiffAcc/. © 2015 The Protein Society.

  20. Modeling the multi-scale mechanisms of macromolecular resource allocation

    DEFF Research Database (Denmark)

    Yang, Laurence; Yurkovich, James T; King, Zachary A

    2018-01-01

    As microbes face changing environments, they dynamically allocate macromolecular resources to produce a particular phenotypic state. Broad 'omics' data sets have revealed several interesting phenomena regarding how the proteome is allocated under differing conditions, but the functional consequen...... and detail how mathematical models have aided in our understanding of these processes. Ultimately, such modeling efforts have helped elucidate the principles of proteome allocation and hold promise for further discovery....

  1. What Macromolecular Crowding Can Do to a Protein

    Science.gov (United States)

    Kuznetsova, Irina M.; Turoverov, Konstantin K.; Uversky, Vladimir N.

    2014-01-01

    The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area. PMID:25514413

  2. Macromolecular target prediction by self-organizing feature maps.

    Science.gov (United States)

    Schneider, Gisbert; Schneider, Petra

    2017-03-01

    Rational drug discovery would greatly benefit from a more nuanced appreciation of the activity of pharmacologically active compounds against a diverse panel of macromolecular targets. Already, computational target-prediction models assist medicinal chemists in library screening, de novo molecular design, optimization of active chemical agents, drug re-purposing, in the spotting of potential undesired off-target activities, and in the 'de-orphaning' of phenotypic screening hits. The self-organizing map (SOM) algorithm has been employed successfully for these and other purposes. Areas covered: The authors recapitulate contemporary artificial neural network methods for macromolecular target prediction, and present the basic SOM algorithm at a conceptual level. Specifically, they highlight consensus target-scoring by the employment of multiple SOMs, and discuss the opportunities and limitations of this technique. Expert opinion: Self-organizing feature maps represent a straightforward approach to ligand clustering and classification. Some of the appeal lies in their conceptual simplicity and broad applicability domain. Despite known algorithmic shortcomings, this computational target prediction concept has been proven to work in prospective settings with high success rates. It represents a prototypic technique for future advances in the in silico identification of the modes of action and macromolecular targets of bioactive molecules.

  3. Induction and Rationalization of Supramolecular Chirality in the Tweezer-Diamine Complexes: Insights from Experimental and DFT Studies.

    Science.gov (United States)

    Dhamija, Avinash; Ikbal, Sk Asif; Rath, Sankar Prasad

    2016-12-19

    A series of supramolecular chiral 1:1 sandwich complexes (1 M ·L and 2 M ·L) consisting of diphenylether/ethane bridged metallobisporphyrin host (1 M and 2 M ; M: Zn/Mg) and chiral diamine guest (L) have been presented. The host-guest complexes are compared just upon changing the metal ion (Mg vs Zn) or the bridge (highly flexible ethane vs rigid diphenylether) keeping other factors similar. The factors that would influence the chirality induction process along with their contributions toward the sign and intensity of the CD couplet of the overall complex have been analyzed. Larger CD amplitude was observed in the host-guest complex with the more flexible ethane bridge as compared to the rigid diphenylether bridged one, irrespective of the metal ion used. Also, Zn complexes have displayed larger CD amplitude because of their stronger binding with the chiral diamines. A fairly linear dependence between the binding constant (K) and CD amplitude has been observed. Moreover, the amplitude of the CD couplet has been correlated with the relative steric bulk of the substituent at the stereogenic center: with increasing the bulk, CD intensity gradually increases. However, large increase of steric hindrance, after a threshold value, has diminished the intensity. The observation of a weak positive CD couplet between (1R,2R)-DPEA guest and Zn-bisporphyrin hosts indicates that the clockwise-twisted (steric-controlled) conformer is more populated as compared to the anticlockwise (chirality-controlled) one. In contrast, amplitude of the positive CD couplets is larger with Mg-bisporphyrin hosts, suggesting almost exclusive contribution of the clockwise-twisted conformer guided solely by sterics. DFT calculations support the experimental observations and have displayed the possible interconversion between clockwise and anticlockwise twisted conformers just upon changing the bulk of the substituent irrespective of the nature of chirality at the stereogenic center.

  4. UQlust: combining profile hashing with linear-time ranking for efficient clustering and analysis of big macromolecular data.

    Science.gov (United States)

    Adamczak, Rafal; Meller, Jarek

    2016-12-28

    Advances in computing have enabled current protein and RNA structure prediction and molecular simulation methods to dramatically increase their sampling of conformational spaces. The quickly growing number of experimentally resolved structures, and databases such as the Protein Data Bank, also implies large scale structural similarity analyses to retrieve and classify macromolecular data. Consequently, the computational cost of structure comparison and clustering for large sets of macromolecular structures has become a bottleneck that necessitates further algorithmic improvements and development of efficient software solutions. uQlust is a versatile and easy-to-use tool for ultrafast ranking and clustering of macromolecular structures. uQlust makes use of structural profiles of proteins and nucleic acids, while combining a linear-time algorithm for implicit comparison of all pairs of models with profile hashing to enable efficient clustering of large data sets with a low memory footprint. In addition to ranking and clustering of large sets of models of the same protein or RNA molecule, uQlust can also be used in conjunction with fragment-based profiles in order to cluster structures of arbitrary length. For example, hierarchical clustering of the entire PDB using profile hashing can be performed on a typical laptop, thus opening an avenue for structural explorations previously limited to dedicated resources. The uQlust package is freely available under the GNU General Public License at https://github.com/uQlust . uQlust represents a drastic reduction in the computational complexity and memory requirements with respect to existing clustering and model quality assessment methods for macromolecular structure analysis, while yielding results on par with traditional approaches for both proteins and RNAs.

  5. A 3D Image Filter for Parameter-Free Segmentation of Macromolecular Structures from Electron Tomograms

    Science.gov (United States)

    Ali, Rubbiya A.; Landsberg, Michael J.; Knauth, Emily; Morgan, Garry P.; Marsh, Brad J.; Hankamer, Ben

    2012-01-01

    3D image reconstruction of large cellular volumes by electron tomography (ET) at high (≤5 nm) resolution can now routinely resolve organellar and compartmental membrane structures, protein coats, cytoskeletal filaments, and macromolecules. However, current image analysis methods for identifying in situ macromolecular structures within the crowded 3D ultrastructural landscape of a cell remain labor-intensive, time-consuming, and prone to user-bias and/or error. This paper demonstrates the development and application of a parameter-free, 3D implementation of the bilateral edge-detection (BLE) algorithm for the rapid and accurate segmentation of cellular tomograms. The performance of the 3D BLE filter has been tested on a range of synthetic and real biological data sets and validated against current leading filters—the pseudo 3D recursive and Canny filters. The performance of the 3D BLE filter was found to be comparable to or better than that of both the 3D recursive and Canny filters while offering the significant advantage that it requires no parameter input or optimisation. Edge widths as little as 2 pixels are reproducibly detected with signal intensity and grey scale values as low as 0.72% above the mean of the background noise. The 3D BLE thus provides an efficient method for the automated segmentation of complex cellular structures across multiple scales for further downstream processing, such as cellular annotation and sub-tomogram averaging, and provides a valuable tool for the accurate and high-throughput identification and annotation of 3D structural complexity at the subcellular level, as well as for mapping the spatial and temporal rearrangement of macromolecular assemblies in situ within cellular tomograms. PMID:22479430

  6. Workshop on algorithms for macromolecular modeling. Final project report, June 1, 1994--May 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Leimkuhler, B.; Hermans, J.; Skeel, R.D.

    1995-07-01

    A workshop was held on algorithms and parallel implementations for macromolecular dynamics, protein folding, and structural refinement. This document contains abstracts and brief reports from that workshop.

  7. The contrasting effect of macromolecular crowding on amyloid fibril formation.

    Directory of Open Access Journals (Sweden)

    Qian Ma

    Full Text Available Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1 have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins.As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3β, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l.We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of proteins (amyloidogenic proteins and non-amyloidogenic proteins has been

  8. Structural analysis of nanoparticulate carriers for encapsulation of macromolecular drugs

    Czech Academy of Sciences Publication Activity Database

    Angelov, Borislav; Garamus, V.M.; Drechsler, M.; Angelova, A.

    2017-01-01

    Roč. 235, Jun (2017), s. 83-89 ISSN 0167-7322 R&D Projects: GA MŠk EF15_003/0000447; GA MŠk EF15_008/0000162 Grant - others:OP VVV - ELIBIO(XE) CZ.02.1.01/0.0/0.0/15_003/0000447; ELI Beamlines(XE) CZ.02.1.01/0.0/0.0/15_008/0000162 Institutional support: RVO:68378271 Keywords : self-assembled nanocarriers * liquid crystalline phase transitions * cationic lipids * macromolecular drugs Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 3.648, year: 2016

  9. Bringing macromolecular machinery to life using 3D animation.

    Science.gov (United States)

    Iwasa, Janet H

    2015-04-01

    Over the past decade, there has been a rapid rise in the use of three-dimensional (3D) animation to depict molecular and cellular processes. Much of the growth in molecular animation has been in the educational arena, but increasingly, 3D animation software is finding its way into research laboratories. In this review, I will discuss a number of ways in which 3d animation software can play a valuable role in visualizing and communicating macromolecular structures and dynamics. I will also consider the challenges of using animation tools within the research sphere. Copyright © 2015. Published by Elsevier Ltd.

  10. Protein crystal growth studies at the Center for Macromolecular Crystallography

    International Nuclear Information System (INIS)

    DeLucas, Lawrence J.; Long, Marianna M.; Moore, Karen M.; Harrington, Michael; McDonald, William T.; Smith, Craig D.; Bray, Terry; Lewis, Johanna; Crysel, William B.; Weise, Lance D.

    2000-01-01

    The Center for Macromolecular Crystallography (CMC) has been involved in fundamental studies of protein crystal growth (PCG) in microgravity and in our earth-based laboratories. A large group of co-investigators from academia and industry participated in these experiments by providing protein samples and by performing the x-ray crystallographic analysis. These studies have clearly demonstrated the usefulness of a microgravity environment for enhancing the quality and size of protein crystals. Review of the vapor diffusion (VDA) PCG results from nineteen space shuttle missions is given in this paper

  11. Modified gum Arabic hydrogels as matrices for controlled release of curcumin supramolecular complexes; Hidrogeis de goma arabica modificada como matrizes para libertacao controlada de complexos supramoleculares de curcumina

    Energy Technology Data Exchange (ETDEWEB)

    Gerola, Adriana P.; Silva, Danielle C., E-mail: avalente@ci.uc.pt [Department of Chemistry, University of Coimbra, Coimbra (Portugal); Rubira, Adley F.; Muniz, Edvani C. [Universidade Estadual de Maringa (GMPC/UEM), PR (Brazil). Grupo de Materiais Polimericos e Compositos; Jesus, Sandra; Borges, Olga [Faculty of Pharmacy, University of Coimbra, Coimbra (Portugal)

    2015-07-01

    Modified gum Arabic (GA) hydrogels show a pH-responsive behavior making them excellent matrices to be used for oral administration of drugs. Our goal is to study the behavior of those matrices in simulated gastric and intestinal fluids. In this work we will present how the methacrylation degree of GA, by using glycidyl methacrylate, can affect the properties of these hydrogels for controlled release. The drug used in this work is the curcumin (Cur). Cur is associated with numerous pharmacological activities, but their application is limited by the low water solubility. We will present some studies involving the formation of host-guest complexes between Cur and natural cyclodextrins. Both modified GA and hydrogels were characterized by different techniques. The kinetics release of Cur complex-containing modified GA hydrogels was studied to have an insight on the release mechanism and rate constants. Toxicity studies on undifferentiated and differentiated Caco-2 were also carried out. (author)

  12. Thiomers for oral delivery of hydrophilic macromolecular drugs.

    Science.gov (United States)

    Bernkop-Schnürch, Andreas; Hoffer, Martin H; Kafedjiiski, Krum

    2004-11-01

    In recent years thiolated polymers (thiomers) have appeared as a promising new tool in oral drug delivery. Thiomers are obtained by the immobilisation of thio-bearing ligands to mucoadhesive polymeric excipients. By the formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of thiomers are up to 130-fold improved compared with the corresponding unmodified polymers. Owing to the formation of inter- and intramolecular disulfide bonds within the thiomer itself, matrix tablets and particulate delivery systems show strong cohesive properties, resulting in comparatively higher stability, prolonged disintegration times and a more controlled drug release. The permeation of hydrophilic macromolecular drugs through the gastrointestinal (GI) mucosa can be improved by the use of thiomers. Furthermore, some thiomers exhibit improved inhibitory properties towards GI peptidases. The efficacy of thiomers in oral drug delivery has been demonstrated by various in vivo studies. A pharmacological efficacy of 1%, for example, was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Furthermore, tablets comprising a thiomer and pegylated insulin resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Low-molecular-weight heparin embedded in thiolated polycarbophil led to an absolute bioavailability of > or = 20% after oral administration to rats. In these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. These results indicate drug carrier systems based on thiomers appear to be a promising tool for oral delivery of hydrophilic macromolecular drugs.

  13. Outrunning free radicals in room-temperature macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Owen, Robin L., E-mail: robin.owen@diamond.ac.uk; Axford, Danny [Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom); Nettleship, Joanne E.; Owens, Raymond J. [Rutherford Appleton Laboratory, Didcot OX11 0FA (United Kingdom); The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Robinson, James I.; Morgan, Ann W. [University of Leeds, Leeds LS9 7FT (United Kingdom); Doré, Andrew S. [Heptares Therapeutics Ltd, BioPark, Welwyn Garden City AL7 3AX (United Kingdom); Lebon, Guillaume; Tate, Christopher G. [MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH (United Kingdom); Fry, Elizabeth E.; Ren, Jingshan [The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Stuart, David I. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom); The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Evans, Gwyndaf [Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom)

    2012-06-15

    A systematic increase in lifetime is observed in room-temperature protein and virus crystals through the use of reduced exposure times and a fast detector. A significant increase in the lifetime of room-temperature macromolecular crystals is reported through the use of a high-brilliance X-ray beam, reduced exposure times and a fast-readout detector. This is attributed to the ability to collect diffraction data before hydroxyl radicals can propagate through the crystal, fatally disrupting the lattice. Hydroxyl radicals are shown to be trapped in amorphous solutions at 100 K. The trend in crystal lifetime was observed in crystals of a soluble protein (immunoglobulin γ Fc receptor IIIa), a virus (bovine enterovirus serotype 2) and a membrane protein (human A{sub 2A} adenosine G-protein coupled receptor). The observation of a similar effect in all three systems provides clear evidence for a common optimal strategy for room-temperature data collection and will inform the design of future synchrotron beamlines and detectors for macromolecular crystallography.

  14. Outrunning free radicals in room-temperature macromolecular crystallography

    International Nuclear Information System (INIS)

    Owen, Robin L.; Axford, Danny; Nettleship, Joanne E.; Owens, Raymond J.; Robinson, James I.; Morgan, Ann W.; Doré, Andrew S.; Lebon, Guillaume; Tate, Christopher G.; Fry, Elizabeth E.; Ren, Jingshan; Stuart, David I.; Evans, Gwyndaf

    2012-01-01

    A systematic increase in lifetime is observed in room-temperature protein and virus crystals through the use of reduced exposure times and a fast detector. A significant increase in the lifetime of room-temperature macromolecular crystals is reported through the use of a high-brilliance X-ray beam, reduced exposure times and a fast-readout detector. This is attributed to the ability to collect diffraction data before hydroxyl radicals can propagate through the crystal, fatally disrupting the lattice. Hydroxyl radicals are shown to be trapped in amorphous solutions at 100 K. The trend in crystal lifetime was observed in crystals of a soluble protein (immunoglobulin γ Fc receptor IIIa), a virus (bovine enterovirus serotype 2) and a membrane protein (human A 2A adenosine G-protein coupled receptor). The observation of a similar effect in all three systems provides clear evidence for a common optimal strategy for room-temperature data collection and will inform the design of future synchrotron beamlines and detectors for macromolecular crystallography

  15. Variable effects of soman on macromolecular secretion by ferret trachea

    International Nuclear Information System (INIS)

    McBride, R.K.; Zwierzynski, D.J.; Stone, K.K.; Culp, D.J.; Marin, M.G.

    1991-01-01

    The purpose of this study was to examine the effect of the anticholinesterase agent, soman, on macromolecular secretion by ferret trachea, in vitro. We mounted pieces of ferret trachea in Ussing-type chambers. Secreted sulfated macromolecules were radiolabeled by adding 500 microCi of 35 SO 4 to the submucosal medium and incubating for 17 hr. Soman added to the submucosal side produced a concentration-dependent increase in radiolabeled macromolecular release with a maximal secretory response (mean +/- SD) of 202 +/- 125% (n = 8) relative to the basal secretion rate at a concentration of 10 - 7 M. The addition of either 10 -6 M pralidoxime (acetylcholinesterase reactivator) or 10 -6 M atropine blocked the response to 10 -7 M soman. At soman concentrations greater than 10 -7 M, secretion rate decreased and was not significantly different from basal secretion. Additional experiments utilizing acetylcholine and the acetylcholinesterase inhibitor, physostigmine, suggest that inhibition of secretion by high concentrations of soman may be due to a secondary antagonistic effect of soman on muscarinic receptors

  16. Dendrimer-based Macromolecular MRI Contrast Agents: Characteristics and Application

    Directory of Open Access Journals (Sweden)

    Hisataka Kobayashi

    2003-01-01

    Full Text Available Numerous macromolecular MRI contrast agents prepared employing relatively simple chemistry may be readily available that can provide sufficient enhancement for multiple applications. These agents operate using a ~100-fold lower concentration of gadolinium ions in comparison to the necessary concentration of iodine employed in CT imaging. Herein, we describe some of the general potential directions of macromolecular MRI contrast agents using our recently reported families of dendrimer-based agents as examples. Changes in molecular size altered the route of excretion. Smaller-sized contrast agents less than 60 kDa molecular weight were excreted through the kidney resulting in these agents being potentially suitable as functional renal contrast agents. Hydrophilic and larger-sized contrast agents were found better suited for use as blood pool contrast agents. Hydrophobic variants formed with polypropylenimine diaminobutane dendrimer cores created liver contrast agents. Larger hydrophilic agents are useful for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents, which also might be employed as therapeutic drugs for either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

  17. PRIGo: a new multi-axis goniometer for macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Waltersperger, Sandro; Olieric, Vincent, E-mail: vincent.olieric@psi.ch; Pradervand, Claude [Paul Scherrer Institute, Villigen PSI (Switzerland); Glettig, Wayne [Centre Suisse d’Electronique et Microtechnique SA, Neuchâtel 2002 (Switzerland); Salathe, Marco; Fuchs, Martin R.; Curtin, Adrian; Wang, Xiaoqiang; Ebner, Simon; Panepucci, Ezequiel; Weinert, Tobias [Paul Scherrer Institute, Villigen PSI (Switzerland); Schulze-Briese, Clemens [Dectris Ltd, Baden 5400 (Switzerland); Wang, Meitian, E-mail: vincent.olieric@psi.ch [Paul Scherrer Institute, Villigen PSI (Switzerland)

    2015-05-09

    The design and performance of the new multi-axis goniometer PRIGo developed at the Swiss Light Source at Paul Scherrer Institute is described. The Parallel Robotics Inspired Goniometer (PRIGo) is a novel compact and high-precision goniometer providing an alternative to (mini-)kappa, traditional three-circle goniometers and Eulerian cradles used for sample reorientation in macromolecular crystallography. Based on a combination of serial and parallel kinematics, PRIGo emulates an arc. It is mounted on an air-bearing stage for rotation around ω and consists of four linear positioners working synchronously to achieve x, y, z translations and χ rotation (0–90°), followed by a ϕ stage (0–360°) for rotation around the sample holder axis. Owing to the use of piezo linear positioners and active correction, PRIGo features spheres of confusion of <1 µm, <7 µm and <10 µm for ω, χ and ϕ, respectively, and is therefore very well suited for micro-crystallography. PRIGo enables optimal strategies for both native and experimental phasing crystallographic data collection. Herein, PRIGo hardware and software, its calibration, as well as applications in macromolecular crystallography are described.

  18. Data Management System at the Photon Factory Macromolecular Crystallography Beamline

    International Nuclear Information System (INIS)

    Yamada, Y; Matsugaki, N; Chavas, L M G; Hiraki, M; Igarashi, N; Wakatsuki, S

    2013-01-01

    Macromolecular crystallography is a very powerful tool to investigate three-dimensional structures of macromolecules at the atomic level, and is widely spread among structural biology researchers. Due to recent upgrades of the macromolecular crystallography beamlines at the Photon Factory, beamline throughput has improved, allowing more experiments to be conducted during a user's beam time. Although the number of beamlines has increased, so has the number of beam time applications. Consequently, both the experimental data from users' experiments and data derived from beamline operations have dramatically increased, causing difficulties in organizing these diverse and large amounts of data for the beamline operation staff and users. To overcome this problem, we have developed a data management system by introducing commercial middleware, which consists of a controller, database, and web servers. We have prepared several database projects using this system. Each project is dedicated to a certain aspect such as experimental results, beam time applications, beam time schedule, or beamline operation reports. Then we designed a scheme to link all the database projects.

  19. Enzymes as Green Catalysts for Precision Macromolecular Synthesis.

    Science.gov (United States)

    Shoda, Shin-ichiro; Uyama, Hiroshi; Kadokawa, Jun-ichi; Kimura, Shunsaku; Kobayashi, Shiro

    2016-02-24

    The present article comprehensively reviews the macromolecular synthesis using enzymes as catalysts. Among the six main classes of enzymes, the three classes, oxidoreductases, transferases, and hydrolases, have been employed as catalysts for the in vitro macromolecular synthesis and modification reactions. Appropriate design of reaction including monomer and enzyme catalyst produces macromolecules with precisely controlled structure, similarly as in vivo enzymatic reactions. The reaction controls the product structure with respect to substrate selectivity, chemo-selectivity, regio-selectivity, stereoselectivity, and choro-selectivity. Oxidoreductases catalyze various oxidation polymerizations of aromatic compounds as well as vinyl polymerizations. Transferases are effective catalysts for producing polysaccharide having a variety of structure and polyesters. Hydrolases catalyzing the bond-cleaving of macromolecules in vivo, catalyze the reverse reaction for bond forming in vitro to give various polysaccharides and functionalized polyesters. The enzymatic polymerizations allowed the first in vitro synthesis of natural polysaccharides having complicated structures like cellulose, amylose, xylan, chitin, hyaluronan, and chondroitin. These polymerizations are "green" with several respects; nontoxicity of enzyme, high catalyst efficiency, selective reactions under mild conditions using green solvents and renewable starting materials, and producing minimal byproducts. Thus, the enzymatic polymerization is desirable for the environment and contributes to "green polymer chemistry" for maintaining sustainable society.

  20. Progress in rational methods of cryoprotection in macromolecular crystallography

    International Nuclear Information System (INIS)

    Alcorn, Thomas; Juers, Douglas H.

    2010-01-01

    Measurements of the average thermal contractions (294→72 K) of 26 different cryosolutions are presented and discussed in conjunction with other recent advances in the rational design of protocols for cryogenic cooling in macromolecular crystallography. Cryogenic cooling of macromolecular crystals is commonly used for X-ray data collection both to reduce crystal damage from radiation and to gather functional information by cryogenically trapping intermediates. However, the cooling process can damage the crystals. Limiting cooling-induced crystal damage often requires cryoprotection strategies, which can involve substantial screening of solution conditions and cooling protocols. Here, recent developments directed towards rational methods for cryoprotection are described. Crystal damage is described in the context of the temperature response of the crystal as a thermodynamic system. As such, the internal and external parts of the crystal typically have different cryoprotection requirements. A key physical parameter, the thermal contraction, of 26 different cryoprotective solutions was measured between 294 and 72 K. The range of contractions was 2–13%, with the more polar cryosolutions contracting less. The potential uses of these results in the development of cryocooling conditions, as well as recent developments in determining minimum cryosolution soaking times, are discussed

  1. Alkali-crown ether complexes at metal surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Thontasen, Nicha; Deng, Zhitao; Rauschenbach, Stephan [Max Planck Institute for Solid State Research, Stuttgart (Germany); Levita, Giacomo [University of Trieste, Trieste (Italy); Malinowski, Nikola [Max Planck Institute for Solid State Research, Stuttgart (Germany); Bulgarian Academy of Sciences, Sofia (Bulgaria); Kern, Klaus [Max Planck Institute for Solid State Research, Stuttgart (Germany); EPFL, Lausanne (Switzerland)

    2010-07-01

    Crown ethers are polycyclic ethers which, in solution, selectively bind cations depending on the size of the ring cavity. The study of a single host-guest complex is highly desirable in order to reveal the characteristics of these specific interactions at the atomic scale. Such detailed investigation is possible at the surface where high resolution imaging tools like scanning tunneling microscopy (STM) can be applied. Here, electrospray ion beam deposition (ES-IBD) is employed for the deposition of Dibenzo-24-crown-8 (DB24C8)-H{sup +}, -Na{sup +} and -Cs{sup +} complexes on a solid surface in ultrahigh vacuum (UHV). Where other deposition techniques have not been successful, this deposition technique combines the advantages of solution based preparation of the complex ions with a highly clean and controlled deposition in UHV. Single molecular structures and the cation-binding of DB24C8 at the surface are studied in situ by STM and MALDI-MS (matrix assisted laser desorption ionization mass spectrometry). The internal structure of the complex, i.e. ring and cavity, is observable only when alkali cations are incorporated. The BD24C8-H{sup +} complex in contrast appears as a compact feature. This result is in good agreement with theoretical models based on density functional theory calculations.

  2. Macromolecular crowding directs extracellular matrix organization and mesenchymal stem cell behavior.

    Directory of Open Access Journals (Sweden)

    Adam S Zeiger

    Full Text Available Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs via immunocytochemistry, atomic force microscopy (AFM, and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro.

  3. Macromolecular crowding directs extracellular matrix organization and mesenchymal stem cell behavior.

    Science.gov (United States)

    Zeiger, Adam S; Loe, Felicia C; Li, Ran; Raghunath, Michael; Van Vliet, Krystyn J

    2012-01-01

    Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro.

  4. Recent Major Improvements to the ALS Sector 5 Macromolecular Crystallography Beamlines

    International Nuclear Information System (INIS)

    Morton, Simon A.; Glossinger, James; Smith-Baumann, Alexis; McKean, John P.; Trame, Christine; Dickert, Jeff; Rozales, Anthony; Dauz, Azer; Taylor, John; Zwart, Petrus; Duarte, Robert; Padmore, Howard; McDermott, Gerry; Adams, Paul

    2007-01-01

    Although the Advanced Light Source (ALS) was initially conceived primarily as a low energy (1.9GeV) 3rd generation source of VUV and soft x-ray radiation it was realized very early in the development of the facility that a multipole wiggler source coupled with high quality, (brightness preserving), optics would result in a beamline whose performance across the optimal energy range (5-15keV) for macromolecular crystallography (MX) would be comparable to, or even exceed, that of many existing crystallography beamlines at higher energy facilities. Hence, starting in 1996, a suite of three beamlines, branching off a single wiggler source, was constructed, which together formed the ALS Macromolecular Crystallography Facility. From the outset this facility was designed to cater equally to the needs of both academic and industrial users with a heavy emphasis placed on the development and introduction of high throughput crystallographic tools, techniques, and facilities--such as large area CCD detectors, robotic sample handling and automounting facilities, a service crystallography program, and a tightly integrated, centralized, and highly automated beamline control environment for users. This facility was immediately successful, with the primary Multiwavelength Anomalous Diffraction beamline (5.0.2) in particular rapidly becoming one of the foremost crystallographic facilities in the US--responsible for structures such as the 70S ribosome. This success in-turn triggered enormous growth of the ALS macromolecular crystallography community and spurred the development of five additional ALS MX beamlines all utilizing the newly developed superconducting bending magnets ('superbends') as sources. However in the years since the original Sector 5.0 beamlines were built the performance demands of macromolecular crystallography users have become ever more exacting; with growing emphasis placed on studying larger complexes, more difficult structures, weakly diffracting or smaller

  5. 50th Anniversary Perspective: Polymers with Complex Architectures

    KAUST Repository

    Polymeropoulos, George; Zapsas, George; Ntetsikas, Konstantinos; Bilalis, Panayiotis; Gnanou, Yves; Hadjichristidis, Nikolaos

    2017-01-01

    The scope of this Perspective is to highlight innovative contributions in the synthesis of well-defined complex macromolecular architectures and to emphasize the importance of these materials to polymer physical chemistry, physics, theory

  6. HOST-GUEST INTERACTION OF PESTICIDE BIFENOX WITH CYCLODEXTRIN MOLECULES. AN ELECTROCHEMICAL STUDY

    Czech Academy of Sciences Publication Activity Database

    Hromadová, Magdaléna; Sokolová, Romana; Pospíšil, Lubomír; Lachmanová, Štěpánka; Fanelli, N.; Giannarelli, S.

    2009-01-01

    Roč. 74, 11-12 (2009), s. 1647-1664 ISSN 0010-0765 R&D Projects: GA AV ČR IAA400400802; GA ČR GA203/08/1157; GA ČR GA203/09/0705; GA ČR GA203/09/1607; GA MŠk LC510; GA MŠk OC 140 Institutional research plan: CEZ:AV0Z40400503 Keywords : reductions * electroreduction * nitro anion radical * electrochemistry Subject RIV: CG - Electrochemistry Impact factor: 0.856, year: 2009

  7. Carbohydrate Nanotechnology: Hierarchical Assemblies and Information Processing with Oligosaccharide-Synthetic Lectin Host-Guest Systems

    Science.gov (United States)

    2013-08-05

    Carbohydrates were explored as targets for synthetic receptors, in nanopatterning, and for directing the movement of nanoswimmers. A synthetic...dimensional movement of rods with translational and rotational diffusion coefficients and Dr respectively, neglecting the difference in...consistent with the previous theories. In the absence of flipping (f = 0), the diffusivity reduces to that of Brownian motion in circles. Neither of

  8. Charge transport in disordered organic host-guest systems: effects of carrier density and electric field

    NARCIS (Netherlands)

    Yimer, Y.Y.; Bobbert, P.A.; Coehoorn, R.

    2008-01-01

    We investigate charge transport in disordered organic host–guest systems with a bimodal Gaussian density of states (DOS). The energy difference between the two Gaussians defines the trap depth. By solving the Pauli master equation for the hopping of charge carriers on a regular lattice with site

  9. Charge transport in disordered organic host-guest systems: effects of carrier density and electric field

    NARCIS (Netherlands)

    Yimer, Y.Y.; Bobbert, P.A.; Coehoorn, R.

    2009-01-01

    We investigate charge transport in disordered organic host–guest systems with a bimodal Gaussian density of states. The energy difference between the peaks of the two Gaussians defines the trap depth. By solving the Pauli master equation for the hopping of charge carriers on a regular lattice we

  10. Easily Processed Host-Guest Polymer Systems with High-Tg Characteristics (First-year Report)

    Science.gov (United States)

    2012-05-01

    manner such that the effective electro- optical coefficient is maximized. Unfortunately, relaxation of the chromophore in the host polymer leads to...polished stainless steel facing plates (0.25 in thickness, McMaster ) and window molds cut from aluminum stock (1 mm thickness, McMaster ). Both facing...plasticization from the chromophore. Both chromophores resulted in substantial red-shifted absorption compared to a sample prepared in virgin PMMA. We expect

  11. Uniaxial negative thermal expansion facilitated by weak host-guest interactions.

    Science.gov (United States)

    Engel, Emile R; Smith, Vincent J; Bezuidenhout, Charl X; Barbour, Leonard J

    2014-04-25

    A nitromethane solvate of 18-crown-6 was investigated by means of variable-temperature single-crystal X-ray diffraction in response to a report of abnormal unit cell contraction. Exceptionally large positive thermal expansion in two axial directions and negative thermal expansion along the third was confirmed. The underlying mechanism relies exclusively on weak electrostatic interactions to yield a linear thermal expansion coefficient of -129 × 10(-6) K(-1), the largest negative value yet observed for an organic inclusion compound.

  12. Molecular Recognition of Vesicles : Host-Guest Interactions Combined with Specific Dimerization of Zwitterions

    NARCIS (Netherlands)

    Voskuhl, Jens; Fenske, Tassilo; Stuart, Marc C. A.; Wibbeling, Birgit; Schmuck, Carsten; Ravoo, Bart Jan

    2010-01-01

    The aggregation of beta-cyclodextrin vesicles can be induced by an adamantyl-substituted zwitterionic guanidiniocarbonylpyrrole carboxylate guest molecule (1). Upon addition of 1 to the cyclodextrin vesicles at neutral pH, the vesicles aggregate (but do not fuse), as shown by using UV/Vis and

  13. Nuclear magnetic resonance titration studies of simple host-guest amine-carboxylic acid systems

    International Nuclear Information System (INIS)

    Mahinay, Myrna S.; Lindoy, Leonard F.

    1999-01-01

    Adduct formation for the open-chain 1,2-diaminoethane and its N-methyl derivatives [N,N-dimethyl-ethylenediamine (N,N-DMEN),N,N'-dimethylethylenediamine (N,N'-DMEN);N,N,N',N'-tetramethyl-ethylenediamine (N,N,N',N'-TMEN)]; 1,4-diaminobutane; diethylenetriamine (DIEN); triethylenetramine (TRIEN); and the carboxylic acid systems in polar CD 3 OH and nonpolar CDCl 3 solvents were elucidated by nmr titration. The stoichiometries of the adducts were found to correspond to the number of nitrogen present in the amine species with the exception of ligand incorporating N-donors of low basicity; that is, whose log K values for the protonated species in water were less than approximately 6 to 7.(Author)

  14. In-vacuum long-wavelength macromolecular crystallography.

    Science.gov (United States)

    Wagner, Armin; Duman, Ramona; Henderson, Keith; Mykhaylyk, Vitaliy

    2016-03-01

    Structure solution based on the weak anomalous signal from native (protein and DNA) crystals is increasingly being attempted as part of synchrotron experiments. Maximizing the measurable anomalous signal by collecting diffraction data at longer wavelengths presents a series of technical challenges caused by the increased absorption of X-rays and larger diffraction angles. A new beamline at Diamond Light Source has been built specifically for collecting data at wavelengths beyond the capability of other synchrotron macromolecular crystallography beamlines. Here, the theoretical considerations in support of the long-wavelength beamline are outlined and the in-vacuum design of the endstation is discussed, as well as other hardware features aimed at enhancing the accuracy of the diffraction data. The first commissioning results, representing the first in-vacuum protein structure solution, demonstrate the promising potential of the beamline.

  15. Efficient analysis of macromolecular rotational diffusion from heteronuclear relaxation data

    International Nuclear Information System (INIS)

    Dosset, Patrice; Hus, Jean-Christophe; Blackledge, Martin; Marion, Dominique

    2000-01-01

    A novel program has been developed for the interpretation of 15 N relaxation rates in terms of macromolecular anisotropic rotational diffusion. The program is based on a highly efficient simulated annealing/minimization algorithm, designed specifically to search the parametric space described by the isotropic, axially symmetric and fully anisotropic rotational diffusion tensor models. The high efficiency of this algorithm allows extensive noise-based Monte Carlo error analysis. Relevant statistical tests are systematically applied to provide confidence limits for the proposed tensorial models. The program is illustrated here using the example of the cytochrome c' from Rhodobacter capsulatus, a four-helix bundle heme protein, for which data at three different field strengths were independently analysed and compared

  16. Macromolecular Crystallization in Microfluidics for the International Space Station

    Science.gov (United States)

    Monaco, Lisa A.; Spearing, Scott

    2003-01-01

    At NASA's Marshall Space Flight Center, the Iterative Biological Crystallization (IBC) project has begun development on scientific hardware for macromolecular crystallization on the International Space Station (ISS). Currently ISS crystallization research is limited to solution recipes that were prepared on the ground prior to launch. The proposed hardware will conduct solution mixing and dispensing on board the ISS, be fully automated, and have imaging functions via remote commanding from the ground. Utilizing microfluidic technology, IBC will allow for on orbit iterations. The microfluidics LabChip(R) devices that have been developed, along with Caliper Technologies, will greatly benefit researchers by allowing for precise fluid handling of nano/pico liter sized volumes. IBC will maximize the amount of science return by utilizing the microfluidic approach and be a valuable tool to structural biologists investigating medically relevant projects.

  17. Macromolecular and dendrimer-based magnetic resonance contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Bumb, Ambika; Brechbiel, Martin W. (Radiation Oncology Branch, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States)), e-mail: pchoyke@mail.nih.gov; Choyke, Peter (Molecular Imaging Program, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States))

    2010-09-15

    Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed

  18. The monitoring system for macromolecular crystallography beamlines at BSRF

    International Nuclear Information System (INIS)

    Guo Xian; Chang Guangcai; Gan Quan; Shi Hong; Liu Peng; Sun Gongxing

    2012-01-01

    The monitoring system for macromolecular crystallography beamlines at BSRF (Beijing Synchrotron Radiation Facility) based on LabVIEW is introduced. In order to guarantee a safe, stable, and reliable running for the beamline devices, the system monitors the state of vacuum, cooling-water, optical components, beam, Liquid nitrogen in the beamlines in real time, detects faults and gives the alarm timely. System underlying uses the driver developed for the field devices for data acquisition, Data of collection is uploaded to the data-sharing platform makes it accessible via a network share. The upper system divides modules according to the actual function, and establishes the main interface of the monitoring system of beamline. To Facilitate data storage, management and inquiry, the system use LabSQL toolkit to achieve the interconnection with MySQL database which data of collection is sent to. (authors)

  19. 129 Xe NMR Relaxation-Based Macromolecular Sensing

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Muller D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Dao, Phuong [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Jeong, Keunhong [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Slack, Clancy C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Vassiliou, Christophoros C. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Finbloom, Joel A. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Francis, Matthew B. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Wemmer, David E. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division; Pines, Alexander [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    2016-07-29

    A 129Xe NMR relaxation-based sensing approach is reported on that exploits changes in the bulk xenon relaxation rate induced by slowed tumbling of a cryptophane-based sensor upon target binding. The amplification afforded by detection of the bulk dissolved xenon allows sensitive detection of targets. The sensor comprises a xenon-binding cryptophane cage, a target interaction element, and a metal chelating agent. Xenon associated with the target-bound cryptophane cage is rapidly relaxed and then detected after exchange with the bulk. Here we show that large macromolecular targets increase the rotational correlation time of xenon, increasing its relaxation rate. Upon binding of a biotin-containing sensor to avidin at 1.5 μM concentration, the free xenon T2 is reduced by a factor of 4.

  20. E-MSD: the European Bioinformatics Institute Macromolecular Structure Database.

    Science.gov (United States)

    Boutselakis, H; Dimitropoulos, D; Fillon, J; Golovin, A; Henrick, K; Hussain, A; Ionides, J; John, M; Keller, P A; Krissinel, E; McNeil, P; Naim, A; Newman, R; Oldfield, T; Pineda, J; Rachedi, A; Copeland, J; Sitnov, A; Sobhany, S; Suarez-Uruena, A; Swaminathan, J; Tagari, M; Tate, J; Tromm, S; Velankar, S; Vranken, W

    2003-01-01

    The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool.

  1. NATO Advanced Study Institute on Evolving Methods for Macromolecular Gystallography

    CERN Document Server

    Read, Randy J

    2007-01-01

    X-ray crystallography is the pre-eminent technique for visualizing the structures of macromolecules at atomic resolution. These structures are central to understanding the detailed mechanisms of biological processes, and to discovering novel therapeutics using a structure-based approach. As yet, structures are known for only a small fraction of the proteins encoded by human and pathogenic genomes. To counter the myriad modern threats of disease, there is an urgent need to determine the structures of the thousands of proteins whose structure and function remain unknown. This volume draws on the expertise of leaders in the field of macromolecular crystallography to illuminate the dramatic developments that are accelerating progress in structural biology. Their contributions span the range of techniques from crystallization through data collection, structure solution and analysis, and show how modern high-throughput methods are contributing to a deeper understanding of medical problems.

  2. MR lymphography with macromolecular Gd-DTPA compounds

    International Nuclear Information System (INIS)

    Hamm, B.; Wagner, S.; Branding, G.; Taupitz, M.; Wolf, K.J.

    1990-01-01

    This paper investigates the suitability of macromolecular Gd-DTPA compounds as signal-enhancing lymphographic agents in MR imaging. Two Gd-DTPA polylysin compounds and Gd-DTPA albumin, with molecular weights of 48,000,170,000, and 87,000 daltons, respectively, were tested in rabbits at gadolinium doses of 5 and 15 μmol per animal. Three animals were examined at each dose with T1-weighted sequences. The iliac lymph nodes were imaged prior to and during unilateral endolymphatic infusion into a femoral lymph vessel as well as over a period of 2 hours thereafter. All contrast media showed a homogeneous and pronounced signal enhancement in the lymph nodes during infusion at both doses

  3. Macromolecular contrast agents for MR mammography: current status

    International Nuclear Information System (INIS)

    Daldrup-Link, Heike E.; Brasch, Robert C.

    2003-01-01

    Macromolecular contrast media (MMCM) encompass a new class of diagnostic drugs that can be applied with dynamic MRI to extract both physiologic and morphologic information in breast lesions. Kinetic analysis of dynamic MMCM-enhanced MR data in breast tumor patients provides useful estimates of tumor blood volume and microvascular permeability, typically increased in cancer. These tumor characteristics can be applied to differentiate benign from malignant lesions, to define the angiogenesis status of cancers, and to monitor tumor response to therapy. The most immediate challenge to the development of MMCM-enhanced mammography is the identification of those candidate compounds that demonstrate the requisite long intravascular distribution and have the high tolerance necessary for clinical use. Potential mammographic applications and limitations of various MMCM, defined by either experimental animal testing or clinical testing in patients, are reviewed in this article. (orig.)

  4. Synthesis of magnetite nanoparticles-β-cyclodextrin complex

    International Nuclear Information System (INIS)

    Cobos Cruz, L.A.; Martinez Perez, C.A.; Monreal Romero, H.A.; Garcia Casillas, P.E.

    2008-01-01

    In this work, the synthesis and characterization of a magnetite (M) and β-cyclodextrin (CD) complex is presented. The chemical bonding between the magnetite and CD was studied as evidence of host-guest interaction; therefore the CD works like a reactor with the magnetite inside of it, as consequence the growth of the particle is restricted by the electrostatic interaction of M-CD complex. The particle size of the magnetite-cyclodextrin complex (M-CD) decreased 79.1% with 0.5% of CD. The average particle size of the M-CD complex was 10 nm. The saturation magnetization (σ s ) and intrinsic coercivity (H c ) increased 10% and 20%, respectively. In order to understand how the the CD affects the results obtained, the second derivate of remission function was obtained from the ultraviolet-visible spectra (UV-vis). Fourier transform infrared spectroscopy (FTIR) was used to elucidate the interaction between the magnetite and CD. The thermal analysis was measured by thermogravimetric and differential thermal analysis (TGA-DTA). The magnetic properties, intrinsic coercivity (H c ) and the saturation magnetization were determined by vibrating sample magnetometry (VSM); the size and shape of nanoparticles were determined by scanning electron microscopy (SEM). The identification of phases was made by X-ray diffraction

  5. Hyperbranched Polyethylenebased Macromolecular Architectures: Synthesis, Characterization, and Selfassembly

    KAUST Repository

    Al-Sulami, Ahlam

    2018-05-01

    "Chain walking” catalytic polymerization CWCP is a powerful tool for the one-pot synthesis of a unique class of hyperbranched polyethylene HBPE-based macromolecules with a controllable molecular weight, topology, and composition. This dissertation focuses on new synthetic routes to prepare HBPE-based macromolecular architectures by combining the CWCP technique with ring opening polymerization ROP, atom–transfer radical polymerization ATRP, and “click” chemistry. Taking advantage of end-functionalized HBPE, and a new ethynyl-soketal star-shape agent, we were able to synthesize different types of the HBPE-based architectures including hyperbranched-on-hyperbranched core-shell nanostructure, and miktoarm-star-HBPE-based block copolymers. The first part of the dissertation provides a general introduction to the synthesis of polyethylene types with controllable structures. Well-defined polyethylene with different macromolecule architectures were synthesized either for academic or industrial purposes. In the second part, the HBPE with different topologies was synthesized by CWCP, using a α-diimine Pd (II) catalyst. The effect of the temperature and pressure on the catalyst activity and polymer properties, including branch content, molecular weight, distribution, and thermal properties were studied. Two series of samples were synthesized: a) serial samples (A) under pressures of 1, 5, and 27 atm at 5˚C, and b) serial samples (B) at temperatures of 5, 15, and 35 ˚C under 5 atm. Proton nuclear magnetic resonance spectroscopy, 1H NMR, and gel permeation chromatography, GPC, analysis were used to calculate the branching content, molecular weight, and distribution, whereas differential scanning calorimetry, DSC, was used to record the melting and glass transition temperatures as well as the degree of the crystallinity. Well-defined HBPE-based core diblock copolymers with predictable amphiphilic properties are studied in the third part of the project. Hyperbranched

  6. The structural biology center at the APS: an integrated user facility for macromolecular crystallography

    International Nuclear Information System (INIS)

    Rosenbaum, G.; Westbrook, E.M.

    1997-01-01

    The Structural Biology Center (SBC) has developed and operates a sector (undulator and bending magnet) of the APS as a user facility for macromolecular crystallography. Crystallographically determined structures of proteins, nucleic acids and their complexes with proteins, viruses, and complexes between macromolecules and small ligands have become of central importance in molecular and cellular biology. Major design goals were to make the extremely high brilliance of the APS available for brilliance limited studies, and to achieve a high throughput of less demanding studies, as well as optimization for MAS-phasing. Crystal samples will include extremely small crystals, crystals with large unit cells (viruses, ribosomes, etc.) and ensembles of closely similar crystal structures for drug design, protein engineering, etc. Data are recorded on a 3000x3000 pixel CCD-area detector (optionally on image plates). The x-ray optics of both beamlines has been designed to produce a highly demagnified image of the source in order to match the focal size with the sizes of the sample and the resolution element of the detector. Vertical focusing is achieved by a flat, cylindrically bent mirror. Horizontal focusing is achieved by sagitally bending the second crystal of the double crystal monochromator. Monochromatic fluxes of 1.3 * 10 13 ph/s into focal sizes of 0.08 mm (horizontal)x0.04 mm (vertical) FWHM (flux density 3.5 * 10 15 ph/s/mm 2 ) have been recorded.copyright 1997 American Institute of Physics

  7. Making microenvironments: A look into incorporating macromolecular crowding into in vitro experiments, to generate biomimetic microenvironments which are capable of directing cell function for tissue engineering applications.

    Science.gov (United States)

    Benny, Paula; Raghunath, Michael

    2017-01-01

    Biomimetic microenvironments are key components to successful cell culture and tissue engineering in vitro. One of the most accurate biomimetic microenvironments is that made by the cells themselves. Cell-made microenvironments are most similar to the in vivo state as they are cell-specific and produced by the actual cells which reside in that specific microenvironment. However, cell-made microenvironments have been challenging to re-create in vitro due to the lack of extracellular matrix composition, volume and complexity which are required. By applying macromolecular crowding to current cell culture protocols, cell-made microenvironments, or cell-derived matrices, can be generated at significant rates in vitro. In this review, we will examine the causes and effects of macromolecular crowding and how it has been applied in several in vitro systems including tissue engineering.

  8. Recent Advances in the Analysis of Macromolecular Interactions Using the Matrix-Free Method of Sedimentation in the Analytical Ultracentrifuge

    Directory of Open Access Journals (Sweden)

    Stephen E. Harding

    2015-03-01

    Full Text Available Sedimentation in the analytical ultracentrifuge is a matrix free solution technique with no immobilisation, columns, or membranes required and can be used to study self-association and complex or “hetero”-interactions, stoichiometry, reversibility and interaction strength of a wide variety of macromolecular types and across a very large dynamic range (dissociation constants from 10−12 M to 10−1 M. We extend an earlier review specifically highlighting advances in sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge applied to protein interactions and mucoadhesion and to review recent applications in protein self-association (tetanus toxoid, agrin, protein-like carbohydrate association (aminocelluloses, carbohydrate-protein interactions (polysaccharide-gliadin, nucleic-acid protein (G-duplexes, nucleic acid-carbohydrate (DNA-chitosan and finally carbohydrate-carbohydrate (xanthan-chitosan and a ternary polysaccharide complex interactions.

  9. Functionalization of Planet-Satellite Nanostructures Revealed by Nanoscopic Localization of Distinct Macromolecular Species

    KAUST Repository

    Rossner, Christian; Roddatis, Vladimir; Lopatin, Sergei; Vana, Philipp

    2016-01-01

    The development of a straightforward method is reported to form hybrid polymer/gold planet-satellite nanostructures (PlSNs) with functional polymer. Polyacrylate type polymer with benzyl chloride in its backbone as a macromolecular tracer

  10. Nitrogen isotopic composition of macromolecular organic matter in interplanetary dust particles

    Science.gov (United States)

    Aléon, Jérôme; Robert, François; Chaussidon, Marc; Marty, Bernard

    2003-10-01

    Nitrogen concentrations and isotopic compositions were measured by ion microprobe scanning imaging in two interplanetary dust particles L2021 K1 and L2036 E22, in which imaging of D/H and C/H ratios has previously evidenced the presence of D-rich macromolecular organic components. High nitrogen concentrations of 10-20 wt% and δ 15N values up to +400‰ are observed in these D-rich macromolecular components. The previous study of D/H and C/H ratios has revealed three different D-rich macromolecular phases. The one previously ascribed to macromolecular organic matter akin the insoluble organic matter (IOM) from carbonaceous chondrites is enriched in nitrogen by one order of magnitude compared to the carbonaceous chondrite IOM, although its isotopic composition is still similar to what is known from Renazzo (δ 15N = +208‰). The correlation observed in macromolecular organic material between the D- and 15N-excesses suggests that the latter originate probably from chemical reactions typical of the cold interstellar medium. These interstellar materials preserved to some extent in IDPs are therefore macromolecular organic components with various aliphaticity and aromaticity. They are heavily N-heterosubstituted as shown by their high nitrogen concentrations >10 wt%. They have high D/H ratios >10 -3 and δ 15N values ≥ +400‰. In L2021 K1 a mixture is observed at the micron scale between interstellar and chondritic-like organic phases. This indicates that some IDPs contain organic materials processed at various heliocentric distances in a turbulent nebula. Comparison with observation in comets suggests that these molecules may be cometary macromolecules. A correlation is observed between the D/H ratios and δ 15N values of macromolecular organic matter from IDPs, meteorites, the Earth and of major nebular reservoirs. This suggests that most macromolecular organic matter in the inner solar system was probably issued from interstellar precursors and further processed

  11. Timely deposition of macromolecular structures is necessary for peer review

    International Nuclear Information System (INIS)

    Joosten, Robbie P.; Soueidan, Hayssam; Wessels, Lodewyk F. A.; Perrakis, Anastassis

    2013-01-01

    Deposition of crystallographic structures should be concurrent with or prior to manuscript submission for peer review, enabling validation and increasing reliability of the PDB. Most of the macromolecular structures in the Protein Data Bank (PDB), which are used daily by thousands of educators and scientists alike, are determined by X-ray crystallography. It was examined whether the crystallographic models and data were deposited to the PDB at the same time as the publications that describe them were submitted for peer review. This condition is necessary to ensure pre-publication validation and the quality of the PDB public archive. It was found that a significant proportion of PDB entries were submitted to the PDB after peer review of the corresponding publication started, and many were only submitted after peer review had ended. It is argued that clear description of journal policies and effective policing is important for pre-publication validation, which is key in ensuring the quality of the PDB and of peer-reviewed literature

  12. Timely deposition of macromolecular structures is necessary for peer review

    Energy Technology Data Exchange (ETDEWEB)

    Joosten, Robbie P. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Soueidan, Hayssam; Wessels, Lodewyk F. A. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam (Netherlands); Perrakis, Anastassis, E-mail: a.perrakis@nki.nl [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands)

    2013-12-01

    Deposition of crystallographic structures should be concurrent with or prior to manuscript submission for peer review, enabling validation and increasing reliability of the PDB. Most of the macromolecular structures in the Protein Data Bank (PDB), which are used daily by thousands of educators and scientists alike, are determined by X-ray crystallography. It was examined whether the crystallographic models and data were deposited to the PDB at the same time as the publications that describe them were submitted for peer review. This condition is necessary to ensure pre-publication validation and the quality of the PDB public archive. It was found that a significant proportion of PDB entries were submitted to the PDB after peer review of the corresponding publication started, and many were only submitted after peer review had ended. It is argued that clear description of journal policies and effective policing is important for pre-publication validation, which is key in ensuring the quality of the PDB and of peer-reviewed literature.

  13. JBluIce-EPICS control system for macromolecular crystallography

    International Nuclear Information System (INIS)

    Stepanov, S.; Makarov, O.; Hilgart, M.; Pothineni, S.; Urakhchin, A.; Devarapalli, S.; Yoder, D.; Becker, M.; Ogata, C.; Sanishvili, R.; Nagarajan, V.; Smith, J.L.; Fischetti, R.F.

    2011-01-01

    The trio of macromolecular crystallography beamlines constructed by the General Medicine and Cancer Institutes Collaborative Access Team (GM/CA-CAT) in Sector 23 of the Advanced Photon Source (APS) have been in growing demand owing to their outstanding beam quality and capacity to measure data from crystals of only a few micrometres in size. To take full advantage of the state-of-the-art mechanical and optical design of these beamlines, a significant effort has been devoted to designing fast, convenient, intuitive and robust beamline controls that could easily accommodate new beamline developments. The GM/CA-CAT beamline controls are based on the power of EPICS for distributed hardware control, the rich Java graphical user interface of Eclipse RCP and the task-oriented philosophy as well as the look and feel of the successful SSRL BluIce graphical user interface for crystallography. These beamline controls feature a minimum number of software layers, the wide use of plug-ins that can be written in any language and unified motion controls that allow on-the-fly scanning and optimization of any beamline component. This paper describes the ways in which BluIce was combined with EPICS and converted into the Java-based JBluIce, discusses the solutions aimed at streamlining and speeding up operations and gives an overview of the tools that are provided by this new open-source control system for facilitating crystallographic experiments, especially in the field of microcrystallography.

  14. Structural changes in the ordering processes of macromolecular compounds

    International Nuclear Information System (INIS)

    Kobayashi, M.; Tashiro, K.

    1998-01-01

    In order to clarify the microscopically-viewed relationship between the conformational ordering process and the aggregation process of the macromolecular chains in the phase transitions from melt to solid or from solution to gel, the time-resolved Fourier-transform infrared spectra and small-angle X-ray or neutron scattering data have been analyzed in an organized manner. Two concrete examples were presented. (1) In the gelation phenomenon of syndiotactic polystyrene-organic solvent system, the ordered TTGG conformation is formed and develops with time. This conformational ordering is accelerated by the aggregation of these chain segments, resulting in the formation of macroscopic gel network. (2) In the isothermal crystallization process from the melt of polyethylene, the following ordering mechanism was revealed. The conformationally-disordered short trans conformers appear at first in the random coils of the melt. These disordered trans sequences grow to longer and more regular trans sequences of the orthorhombic-type crystal and then the isolated lamellae are formed. Afterwards, the stacked lamellar structure is developed without change of lamellar thickness but with small decrease in the long period, indicating an insertion of new lamellae between the already produced lamellar layers

  15. On macromolecular refinement at subatomic resolution with interatomic scatterers

    Energy Technology Data Exchange (ETDEWEB)

    Afonine, Pavel V., E-mail: pafonine@lbl.gov; Grosse-Kunstleve, Ralf W.; Adams, Paul D. [Lawrence Berkeley National Laboratory, One Cyclotron Road, BLDG 64R0121, Berkeley, CA 94720 (United States); Lunin, Vladimir Y. [Institute of Mathematical Problems of Biology, Russian Academy of Sciences, Pushchino 142290 (Russian Federation); Urzhumtsev, Alexandre [IGMBC, 1 Rue L. Fries, 67404 Illkirch and IBMC, 15 Rue R. Descartes, 67084 Strasbourg (France); Faculty of Sciences, Nancy University, 54506 Vandoeuvre-lès-Nancy (France); Lawrence Berkeley National Laboratory, One Cyclotron Road, BLDG 64R0121, Berkeley, CA 94720 (United States)

    2007-11-01

    Modelling deformation electron density using interatomic scatters is simpler than multipolar methods, produces comparable results at subatomic resolution and can easily be applied to macromolecules. A study of the accurate electron-density distribution in molecular crystals at subatomic resolution (better than ∼1.0 Å) requires more detailed models than those based on independent spherical atoms. A tool that is conventionally used in small-molecule crystallography is the multipolar model. Even at upper resolution limits of 0.8–1.0 Å, the number of experimental data is insufficient for full multipolar model refinement. As an alternative, a simpler model composed of conventional independent spherical atoms augmented by additional scatterers to model bonding effects has been proposed. Refinement of these mixed models for several benchmark data sets gave results that were comparable in quality with the results of multipolar refinement and superior to those for conventional models. Applications to several data sets of both small molecules and macromolecules are shown. These refinements were performed using the general-purpose macromolecular refinement module phenix.refine of the PHENIX package.

  16. Polycapillary x-ray optics for macromolecular crystallography

    International Nuclear Information System (INIS)

    Owens, S.M.; Gibson, W.M.; Carter, D.C.; Sisk, R.C.; Ho, J.X.

    1996-01-01

    Polycapillary x-ray optics have found potential application in many different fields, including antiscatter and magnification in mammography, radiography, x-ray fluorescence, x-ray lithography, and x-ray diffraction techniques. In x-ray diffraction, an optic is used to collect divergent x-rays from a point source and redirect them into a quasi-parallel, or slightly focused beam. Monolithic polycapillary optics have been developed recently for macromolecular crystallography and have already shown considerable gains in diffracted beam intensity over pinhole collimation. Development is being pursued through a series of simulations and prototype optics. Many improvements have been made over the stage 1 prototype reported previously, which include better control over the manufacturing process, reducing the diameter of the output beam, and addition of a slight focusing at the output of the optic to further increase x-ray flux at the sample. The authors report the characteristics and performance of the stage 1 and stage 2 optics

  17. A beamline for macromolecular crystallography at the Advanced Light Source

    International Nuclear Information System (INIS)

    Padmore, H.A.; Earnest, T.; Kim, S.H.; Thompson, A.C.; Robinson, A.L.

    1994-08-01

    A beamline for macromolecular crystallography has been designed for the ALS. The source will be a 37-pole wiggler with a, 2-T on-axis peak field. The wiggler will illuminate three beamlines, each accepting 3 mrad of horizontal aperture. The central beamline will primarily be used for multiple-wavelength anomalous dispersion measurements in the wavelength range from 4 to 0.9 angstrom. The beamline optics will comprise a double-crystal monochromator with a collimating pre-mirror and a double-focusing mirror after the monochromator. The two side stations will be used for fixed-wavelength experiments within the wavelength range from 1.5 to 0.95 angstrom. The optics will consist of a conventional vertically focusing cylindrical mirror followed by an asymmetrically cut curved-crystal monochromator. This paper presents details of the optimization of the wiggler source for crystallography, gives a description of the beamline configuration, and discusses the reasons for the choices made

  18. Macromolecular crystallization in microgravity generated by a superconducting magnet.

    Science.gov (United States)

    Wakayama, N I; Yin, D C; Harata, K; Kiyoshi, T; Fujiwara, M; Tanimoto, Y

    2006-09-01

    About 30% of the protein crystals grown in space yield better X-ray diffraction data than the best crystals grown on the earth. The microgravity environments provided by the application of an upward magnetic force constitute excellent candidates for simulating the microgravity conditions in space. Here, we describe a method to control effective gravity and formation of protein crystals in various levels of effective gravity. Since 2002, the stable and long-time durable microgravity generated by a convenient type of superconducting magnet has been available for protein crystal growth. For the first time, protein crystals, orthorhombic lysozyme, were grown at microgravity on the earth, and it was proved that this microgravity improved the crystal quality effectively and reproducibly. The present method always accompanies a strong magnetic field, and the magnetic field itself seems to improve crystal quality. Microgravity is not always effective for improving crystal quality. When we applied this microgravity to the formation of cubic porcine insulin and tetragonal lysozyme crystals, we observed no dependence of effective gravity on crystal quality. Thus, this kind of test will be useful for selecting promising proteins prior to the space experiments. Finally, the microgravity generated by the magnet is compared with that in space, considering the cost, the quality of microgravity, experimental convenience, etc., and the future use of this microgravity for macromolecular crystal growth is discussed.

  19. Macromolecular crystallography with a large format CMOS detector

    Energy Technology Data Exchange (ETDEWEB)

    Nix, Jay C., E-mail: jcnix@lbl.gov [Molecular Biology Consortium 12003 S. Pulaski Rd. #166 Alsip, IL 60803 U.S.A (United States)

    2016-07-27

    Recent advances in CMOS technology have allowed the production of large surface area detectors suitable for macromolecular crystallography experiments [1]. The Molecular Biology Consortium (MBC) Beamline 4.2.2 at the Advanced Light Source in Berkeley, CA, has installed a 2952 x 2820 mm RDI CMOS-8M detector with funds from NIH grant S10OD012073. The detector has a 20nsec dead pixel time and performs well with shutterless data collection strategies. The sensor obtains sharp point response and minimal optical distortion by use of a thin fiber-optic plate between the phosphor and sensor module. Shutterless data collections produce high-quality redundant datasets that can be obtained in minutes. The fine-sliced data are suitable for processing in standard crystallographic software packages (XDS, HKL2000, D*TREK, MOSFLM). Faster collection times relative to the previous CCD detector have resulted in a record number of datasets collected in a calendar year and de novo phasing experiments have resulted in publications in both Science and Nature [2,3]. The faster collections are due to a combination of the decreased overhead requirements of shutterless collections combined with exposure times that have decreased by over a factor of 2 for images with comparable signal to noise of the NOIR-1 detector. The overall increased productivity has allowed the development of new beamline capabilities and data collection strategies.

  20. Macromolecular refinement by model morphing using non-atomic parameterizations.

    Science.gov (United States)

    Cowtan, Kevin; Agirre, Jon

    2018-02-01

    Refinement is a critical step in the determination of a model which explains the crystallographic observations and thus best accounts for the missing phase components. The scattering density is usually described in terms of atomic parameters; however, in macromolecular crystallography the resolution of the data is generally insufficient to determine the values of these parameters for individual atoms. Stereochemical and geometric restraints are used to provide additional information, but produce interrelationships between parameters which slow convergence, resulting in longer refinement times. An alternative approach is proposed in which parameters are not attached to atoms, but to regions of the electron-density map. These parameters can move the density or change the local temperature factor to better explain the structure factors. Varying the size of the region which determines the parameters at a particular position in the map allows the method to be applied at different resolutions without the use of restraints. Potential applications include initial refinement of molecular-replacement models with domain motions, and potentially the use of electron density from other sources such as electron cryo-microscopy (cryo-EM) as the refinement model.

  1. Hypoxic tumor environments exhibit disrupted collagen I fibers and low macromolecular transport.

    Directory of Open Access Journals (Sweden)

    Samata M Kakkad

    Full Text Available Hypoxic tumor microenvironments result in an aggressive phenotype and resistance to therapy that lead to tumor progression, recurrence, and metastasis. While poor vascularization and the resultant inadequate drug delivery are known to contribute to drug resistance, the effect of hypoxia on molecular transport through the interstitium, and the role of the extracellular matrix (ECM in mediating this transport are unexplored. The dense mesh of fibers present in the ECM can especially influence the movement of macromolecules. Collagen 1 (Col1 fibers form a key component of the ECM in breast cancers. Here we characterized the influence of hypoxia on macromolecular transport in tumors, and the role of Col1 fibers in mediating this transport using an MDA-MB-231 breast cancer xenograft model engineered to express red fluorescent protein under hypoxia. Magnetic resonance imaging of macromolecular transport was combined with second harmonic generation microscopy of Col1 fibers. Hypoxic tumor regions displayed significantly decreased Col1 fiber density and volume, as well as significantly lower macromolecular draining and pooling rates, than normoxic regions. Regions adjacent to severely hypoxic areas revealed higher deposition of Col1 fibers and increased macromolecular transport. These data suggest that Col1 fibers may facilitate macromolecular transport in tumors, and their reduction in hypoxic regions may reduce this transport. Decreased macromolecular transport in hypoxic regions may also contribute to poor drug delivery and tumor recurrence in hypoxic regions. High Col1 fiber density observed around hypoxic regions may facilitate the escape of aggressive cancer cells from hypoxic regions.

  2. Rapid automated superposition of shapes and macromolecular models using spherical harmonics.

    Science.gov (United States)

    Konarev, Petr V; Petoukhov, Maxim V; Svergun, Dmitri I

    2016-06-01

    A rapid algorithm to superimpose macromolecular models in Fourier space is proposed and implemented ( SUPALM ). The method uses a normalized integrated cross-term of the scattering amplitudes as a proximity measure between two three-dimensional objects. The reciprocal-space algorithm allows for direct matching of heterogeneous objects including high- and low-resolution models represented by atomic coordinates, beads or dummy residue chains as well as electron microscopy density maps and inhomogeneous multi-phase models ( e.g. of protein-nucleic acid complexes). Using spherical harmonics for the computation of the amplitudes, the method is up to an order of magnitude faster than the real-space algorithm implemented in SUPCOMB by Kozin & Svergun [ J. Appl. Cryst. (2001 ▸), 34 , 33-41]. The utility of the new method is demonstrated in a number of test cases and compared with the results of SUPCOMB . The spherical harmonics algorithm is best suited for low-resolution shape models, e.g . those provided by solution scattering experiments, but also facilitates a rapid cross-validation against structural models obtained by other methods.

  3. Macromolecular weight specificity in covalent binding of bromobenzene

    International Nuclear Information System (INIS)

    Sun, J.D.; Dent, J.G.

    1984-01-01

    Bromobenzene is a hepatotoxicant that causes centrilobular necrosis. Pretreatment of animals with 3-methylcholanthrene decreases and phenobarbital pretreatment enhances the hepatotoxic action of this compound. We have investigated the macromolecular weight specificity of the covalent interactions of bromobenzene with liver macromolecules following incubation of [ 14 C]bromobenzene in isolated hepatocytes. Hepatocytes were prepared from Fischer-344 rats treated for 3 days with 3-methylcholanthrene, phenobarbital, or normal saline. After a 1-hr incubation, total covalent binding, as measured by sodium dodecyl sulfate-equilibrium dialysis, was twofold less in hepatocytes from 3-methylcholanthrene-treated rats and sixfold greater in hepatocytes from phenobarbital-treated rats, as compared to hepatocytes from control animals. Analysis of the arylated macromolecules by electrophoresis on 15% sodium dodecyl sulfate-polyacrylamide disc gels indicated that in the first 1 to 3 min of incubation substantial amounts of covalently bound radiolabel were associated with macromolecules of between 20,000 and 40,000. The amount of radioactivity associated with these macromolecules rapidly diminished in hepatocytes from control and 3-methylcholanthrene-treated animals. In hepatocytes from phenobarbital-treated animals, the amount of radioactivity associated with macromolecules, 20,000, increased throughout the incubation. The amount of radiolabel associated with macromolecules, 20,000, increased in all incubations. When nontoxic doses of phenylmethylsulfonyl fluoride, a specific inhibitor of serine proteases, were added to control hepatocytes incubated with [ 14 C]-bromobenzene, the decrease in radioactivity associated with larger (greater than 20,000) macromolecules was inhibited and a corresponding lack of increase in radioactivity associated with smaller macromolecules was observed

  4. Crystallographic and theoretical studies of an inclusion complex of β-cyclodextrin with fentanyl.

    Science.gov (United States)

    Ogawa, Noriko; Nagase, Hiromasa; Loftsson, Thorsteinn; Endo, Tomohiro; Takahashi, Chisato; Kawashima, Yoshiaki; Ueda, Haruhisa; Yamamoto, Hiromitsu

    2017-10-15

    The crystal structure of an inclusion complex of β-cyclodextrin (β-CD) with fentanyl was determined by single crystal X-ray diffraction analysis. The crystal belongs to the triclinic space group P1 and the complex comprises one fentanyl, two β-CD, and several water molecules. β-CD and fentanyl form a host-guest inclusion complex at a ratio of 2:1 and the asymmetric unit of the complex contains two host molecules (β-CDs) in a head-to-head arrangement that form dimers through hydrogen bonds between the secondary hydroxyl groups of β-CD and one guest molecule. Fentanyl is totally contained within the β-CD cavity and the structure of the phenylethyl part of fentanyl inside the dimeric cavity of the complex is disordered. Furthermore, theoretical molecular conformational calculations were conducted to clarify the mobility of the guest molecule in the β-CD cavity using CONFLEX software. Crystal optimization and crystal energy calculations were also conducted. The results of the theoretical calculations confirmed that the conformation of disorder part 1, which was high in occupancy by crystal structure analysis, was more stable. The phenylethyl part of fentanyl existed in several stable conformations. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

    Directory of Open Access Journals (Sweden)

    Gaetano Malgieri

    2013-06-01

    Full Text Available The aptitude of cyclodextrins (CDs to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA, a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and 1H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC50s and EC90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.

  6. Inclusion Complexes of Sunscreen Agents with β-Cyclodextrin: Spectroscopic and Molecular Modeling Studies

    Directory of Open Access Journals (Sweden)

    Nathir A. F. Al-Rawashdeh

    2013-01-01

    Full Text Available The inclusion complexes of selected sunscreen agents, namely, oxybenzone (Oxy, octocrylene (Oct, and ethylhexyl-methoxycinnamate (Cin with β-cyclodextrin (β-CD were studied by UV-Vis spectroscopy, differential scanning calorimetry (DSC, 13C NMR techniques, and molecular mechanics (MM calculations and modeling. Molecular modeling (MM study of the entire process of the formation of 1 : 1 stoichiometry sunscreen agent/β-cyclodextrin structures has been used to contribute to the understanding and rationalization of the experimental results. Molecular mechanics calculations, together with 13C NMR measurements, for the complex with β-CD have been used to describe details of the structural, energetic, and dynamic features of host-guest complex. Accurate structures of CD inclusion complexes have been derived from molecular mechanics (MM calculations and modeling. The photodegradation reaction of the sunscreen agents' molecules in lotion was explored using UV-Vis spectroscopy. It has been demonstrated that the photostability of these selected sunscreen agents has been enhanced upon forming inclusion complexes with β-CD in lotion. The results of this study demonstrate that β-CD can be utilized as photostabilizer additive for enhancing the photostability of the selected sunscreen agents' molecules.

  7. A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2013-06-01

    A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

  8. Towards a compact and precise sample holder for macromolecular crystallography.

    Science.gov (United States)

    Papp, Gergely; Rossi, Christopher; Janocha, Robert; Sorez, Clement; Lopez-Marrero, Marcos; Astruc, Anthony; McCarthy, Andrew; Belrhali, Hassan; Bowler, Matthew W; Cipriani, Florent

    2017-10-01

    Most of the sample holders currently used in macromolecular crystallography offer limited storage density and poor initial crystal-positioning precision upon mounting on a goniometer. This has now become a limiting factor at high-throughput beamlines, where data collection can be performed in a matter of seconds. Furthermore, this lack of precision limits the potential benefits emerging from automated harvesting systems that could provide crystal-position information which would further enhance alignment at beamlines. This situation provided the motivation for the development of a compact and precise sample holder with corresponding pucks, handling tools and robotic transfer protocols. The development process included four main phases: design, prototype manufacture, testing with a robotic sample changer and validation under real conditions on a beamline. Two sample-holder designs are proposed: NewPin and miniSPINE. They share the same robot gripper and allow the storage of 36 sample holders in uni-puck footprint-style pucks, which represents 252 samples in a dry-shipping dewar commonly used in the field. The pucks are identified with human- and machine-readable codes, as well as with radio-frequency identification (RFID) tags. NewPin offers a crystal-repositioning precision of up to 10 µm but requires a specific goniometer socket. The storage density could reach 64 samples using a special puck designed for fully robotic handling. miniSPINE is less precise but uses a goniometer mount compatible with the current SPINE standard. miniSPINE is proposed for the first implementation of the new standard, since it is easier to integrate at beamlines. An upgraded version of the SPINE sample holder with a corresponding puck named SPINEplus is also proposed in order to offer a homogenous and interoperable system. The project involved several European synchrotrons and industrial companies in the fields of consumables and sample-changer robotics. Manual handling of mini

  9. Effects of macromolecular crowding on protein conformational changes.

    Directory of Open Access Journals (Sweden)

    Hao Dong

    2010-07-01

    Full Text Available Many protein functions can be directly linked to conformational changes. Inside cells, the equilibria and transition rates between different conformations may be affected by macromolecular crowding. We have recently developed a new approach for modeling crowding effects, which enables an atomistic representation of "test" proteins. Here this approach is applied to study how crowding affects the equilibria and transition rates between open and closed conformations of seven proteins: yeast protein disulfide isomerase (yPDI, adenylate kinase (AdK, orotidine phosphate decarboxylase (ODCase, Trp repressor (TrpR, hemoglobin, DNA beta-glucosyltransferase, and Ap(4A hydrolase. For each protein, molecular dynamics simulations of the open and closed states are separately run. Representative open and closed conformations are then used to calculate the crowding-induced changes in chemical potential for the two states. The difference in chemical-potential change between the two states finally predicts the effects of crowding on the population ratio of the two states. Crowding is found to reduce the open population to various extents. In the presence of crowders with a 15 A radius and occupying 35% of volume, the open-to-closed population ratios of yPDI, AdK, ODCase and TrpR are reduced by 79%, 78%, 62% and 55%, respectively. The reductions for the remaining three proteins are 20-44%. As expected, the four proteins experiencing the stronger crowding effects are those with larger conformational changes between open and closed states (e.g., as measured by the change in radius of gyration. Larger proteins also tend to experience stronger crowding effects than smaller ones [e.g., comparing yPDI (480 residues and TrpR (98 residues]. The potentials of mean force along the open-closed reaction coordinate of apo and ligand-bound ODCase are altered by crowding, suggesting that transition rates are also affected. These quantitative results and qualitative trends will

  10. Investigating the inclusion properties of aromatic amino acids complexing beta-cyclodextrins in model peptides.

    Science.gov (United States)

    Caso, Jolanda Valentina; Russo, Luigi; Palmieri, Maddalena; Malgieri, Gaetano; Galdiero, Stefania; Falanga, Annarita; Isernia, Carla; Iacovino, Rosa

    2015-10-01

    Cyclodextrins are commonly used as complexing agents in biological, pharmaceutical, and industrial applications since they have an effect on protein thermal and proteolytic stability, refolding yields, solubility, and taste masking. β-cyclodextrins (β-CD), because of their cavity size are a perfectly suited complexing agent for many common guest moieties. In the case of peptide-cyclodextrin and protein-cyclodextrin host-guest complexes the aromatic amino acids are reported to be the principal responsible of the interaction. For these reasons, we have investigated the inclusion properties of nine designed tripeptides, obtained permuting the position of two L-alanines (Ala, A) with that of one L-tryptophan (Trp, W), L-phenylalanine (Phe, F), or L-tyrosine (Tyr, Y), respectively. Interestingly, the position of the aromatic side-chain in the sequence appears to modulate the β-CD:peptide binding constants, determined via UV-Vis and NMR spectroscopy, which in turn assumes values higher than those reported for the single amino acid. The tripeptides containing a tyrosine showed the highest binding constants, with the central position in the Ac-AYA-NH2 peptide becoming the most favorite for the interaction. A combined NMR and Molecular Docking approach permitted to build detailed complex models, highlighting the stabilizing interactions of the neighboring amino acids backbone atoms with the upper rim of the β-CD.

  11. New Paradigm for Macromolecular Crystallography Experiments at SSRL: Automated Crystal Screening And Remote Data Collection

    International Nuclear Information System (INIS)

    Soltis, S.M.; Cohen, A.E.; Deacon, A.; Eriksson, T.; Gonzalez, A.; McPhillips, S.; Chui, H.; Dunten, P.; Hollenbeck, M.; Mathews, I.; Miller, M.; Moorhead, P.; Phizackerley, R.P.; Smith, C.; Song, J.; Bedem, H. van dem; Ellis, P.; Kuhn, P.; McPhillips, T.; Sauter, N.; Sharp, K.

    2009-01-01

    Complete automation of the macromolecular crystallography experiment has been achieved at Stanford Synchrotron Radiation Lightsource (SSRL) through the combination of robust mechanized experimental hardware and a flexible control system with an intuitive user interface. These highly reliable systems have enabled crystallography experiments to be carried out from the researchers' home institutions and other remote locations while retaining complete control over even the most challenging systems. A breakthrough component of the system, the Stanford Auto-Mounter (SAM), has enabled the efficient mounting of cryocooled samples without human intervention. Taking advantage of this automation, researchers have successfully screened more than 200 000 samples to select the crystals with the best diffraction quality for data collection as well as to determine optimal crystallization and cryocooling conditions. These systems, which have been deployed on all SSRL macromolecular crystallography beamlines and several beamlines worldwide, are used by more than 80 research groups in remote locations, establishing a new paradigm for macromolecular crystallography experimentation.

  12. Assessing Exhaustiveness of Stochastic Sampling for Integrative Modeling of Macromolecular Structures.

    Science.gov (United States)

    Viswanath, Shruthi; Chemmama, Ilan E; Cimermancic, Peter; Sali, Andrej

    2017-12-05

    Modeling of macromolecular structures involves structural sampling guided by a scoring function, resulting in an ensemble of good-scoring models. By necessity, the sampling is often stochastic, and must be exhaustive at a precision sufficient for accurate modeling and assessment of model uncertainty. Therefore, the very first step in analyzing the ensemble is an estimation of the highest precision at which the sampling is exhaustive. Here, we present an objective and automated method for this task. As a proxy for sampling exhaustiveness, we evaluate whether two independently and stochastically generated sets of models are sufficiently similar. The protocol includes testing 1) convergence of the model score, 2) whether model scores for the two samples were drawn from the same parent distribution, 3) whether each structural cluster includes models from each sample proportionally to its size, and 4) whether there is sufficient structural similarity between the two model samples in each cluster. The evaluation also provides the sampling precision, defined as the smallest clustering threshold that satisfies the third, most stringent test. We validate the protocol with the aid of enumerated good-scoring models for five illustrative cases of binary protein complexes. Passing the proposed four tests is necessary, but not sufficient for thorough sampling. The protocol is general in nature and can be applied to the stochastic sampling of any set of models, not just structural models. In addition, the tests can be used to stop stochastic sampling as soon as exhaustiveness at desired precision is reached, thereby improving sampling efficiency; they may also help in selecting a model representation that is sufficiently detailed to be informative, yet also sufficiently coarse for sampling to be exhaustive. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  13. MolProbity: all-atom structure validation for macromolecular crystallography

    International Nuclear Information System (INIS)

    Chen, Vincent B.; Arendall, W. Bryan III; Headd, Jeffrey J.; Keedy, Daniel A.; Immormino, Robert M.; Kapral, Gary J.; Murray, Laura W.; Richardson, Jane S.; Richardson, David C.

    2010-01-01

    MolProbity structure validation will diagnose most local errors in macromolecular crystal structures and help to guide their correction. MolProbity is a structure-validation web service that provides broad-spectrum solidly based evaluation of model quality at both the global and local levels for both proteins and nucleic acids. It relies heavily on the power and sensitivity provided by optimized hydrogen placement and all-atom contact analysis, complemented by updated versions of covalent-geometry and torsion-angle criteria. Some of the local corrections can be performed automatically in MolProbity and all of the diagnostics are presented in chart and graphical forms that help guide manual rebuilding. X-ray crystallography provides a wealth of biologically important molecular data in the form of atomic three-dimensional structures of proteins, nucleic acids and increasingly large complexes in multiple forms and states. Advances in automation, in everything from crystallization to data collection to phasing to model building to refinement, have made solving a structure using crystallography easier than ever. However, despite these improvements, local errors that can affect biological interpretation are widespread at low resolution and even high-resolution structures nearly all contain at least a few local errors such as Ramachandran outliers, flipped branched protein side chains and incorrect sugar puckers. It is critical both for the crystallographer and for the end user that there are easy and reliable methods to diagnose and correct these sorts of errors in structures. MolProbity is the authors’ contribution to helping solve this problem and this article reviews its general capabilities, reports on recent enhancements and usage, and presents evidence that the resulting improvements are now beneficially affecting the global database

  14. Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo.

    Science.gov (United States)

    Akhter, S R; Ikezaki, H; Gao, X P; Rubinstein, I

    1999-05-01

    The purpose of this study was to determine whether dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux from the in situ hamster cheek pouch and, if so, whether this response is specific. By using intravital microscopy, we found that an aqueous extract of grain sorghum dust elicited significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (FITC-dextran; mol mass, 70 kDa) from the in situ hamster cheek pouch (P grain sorghum dust extract- and substance P-induced increases in macromolecular efflux from the in situ hamster cheek pouch in a specific fashion.

  15. An acoustic on-chip goniometer for room temperature macromolecular crystallography.

    Science.gov (United States)

    Burton, C G; Axford, D; Edwards, A M J; Gildea, R J; Morris, R H; Newton, M I; Orville, A M; Prince, M; Topham, P D; Docker, P T

    2017-12-05

    This paper describes the design, development and successful use of an on-chip goniometer for room-temperature macromolecular crystallography via acoustically induced rotations. We present for the first time a low cost, rate-tunable, acoustic actuator for gradual in-fluid sample reorientation about varying axes and its utilisation for protein structure determination on a synchrotron beamline. The device enables the efficient collection of diffraction data via a rotation method from a sample within a surface confined droplet. This method facilitates efficient macromolecular structural data acquisition in fluid environments for dynamical studies.

  16. Aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes as revealed by microscopic radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Tetsuji [Shinshu University, Matsumoto (Japan). Dept. of Anatomy and Cell Biology

    2007-07-01

    This mini-review reports aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes. We have observed the macromolecular synthesis, such as DNA, RNA and proteins, in the mitochondria of various mammalian cells by means of electron microscopic radioautography technique developed in our laboratory. The number of mitochondria per cell, number of labeled mitochondria per cell with 3H-thymidine, 3H-uridine and 3H-leucine, precursors for DNA, RNA and proteins, respectively, were counted and the labeling indices at various ages, from fetal to postnatal early days and several months to 1 and 2 years in senescence, were calculated, which showed variations due to aging. (author)

  17. Nanodiamonds in sugar rings: an experimental and theoretical investigation of cyclodextrin-nanodiamond inclusion complexes.

    Science.gov (United States)

    Voskuhl, Jens; Waller, Mark; Bandaru, Sateesh; Tkachenko, Boryslav A; Fregonese, Carlo; Wibbeling, Birgit; Schreiner, Peter R; Ravoo, Bart Jan

    2012-06-21

    We report on the noncovalent interactions of nanodiamond carboxylic acids derived from adamantane, diamantane, and triamantane with β- and γ-cyclodextrins. The water solubility of the nanodiamonds was increased by attaching an aromatic dicarboxylic acid via peptide coupling. Isothermal titration calorimetry experiments were performed to determine the thermodynamic parameters (K(a), ΔH, ΔG and ΔS) for the host-guest inclusion. The stoichiometry of the complexes is invariably 1:1. It was found that K(a), ΔG and ΔH of inclusion increase for larger nanodiamonds. ΔS is generally positive, in particular for the largest nanodiamonds. β-Cyclodextrin binds all nanodiamonds, γ-cyclodextrin clearly prefers the most bulky nanodiamonds. The interaction of 9-triamantane carboxylic acid shows one of the strongest complexation constants towards γ-cyclodextrin ever reported, K(a) = 5.0 × 10(5) M(-1). In order to gain some insight into the possible structural basis of these inclusion complexes we performed density functional calculations at the B97-D3/def2-TZVPP level of theory.

  18. Comparative In Vitro Controlled Release Studies on the Chronobiotic Hormone Melatonin from Cyclodextrins-Containing Matrices and Cyclodextrin: Melatonin Complexes.

    Science.gov (United States)

    Vlachou, Marilena; Papamichael, Marianna; Siamidi, Angeliki; Fragouli, Irene; Afroudakis, Pandelis A; Kompogennitaki, Rodanthi; Dotsikas, Yannis

    2017-07-28

    A series of hydrophilic matrix tablets was prepared and tested with respect to their ability to release the hormone melatonin in a controlled manner, in order to alleviate sleep onset and sleep maintenance dysfunctions. Besides the active ingredient, the tablets were comprised of combinations of the following: HPMC K 15M, low viscosity sodium alginate, microcrystalline cellulose (Avicel PH 102), magnesium stearate, and the cyclodextrins, α-CD, β-CD, γ-CD, HP-β-CD, sulfated β-CD, HP-α-CD and HP-γ-CD, and MLT (guest):CD (host) complexes of the above cyclodextrins, in 1:1 ratio. The controlled release studies were conducted in two aqueous dissolution media at pH 1.2 and 7.4. The stoichiometry of the formed complexes was examined by applying the continuous variation method (Job plot), while the stability constants were calculated by monitoring the spectrophotometric properties of free and CD-encapsulated melatonin (UV-Vis). Host-guest interactions were studied by Nuclear Magnetic Resonance (NMR) spectroscopy. The dissolution data suggest that melatonin is released faster from the MLT:CD complexes than from the rest matrix systems. This enhancement in the dissolution rate and the % release of melatonin from the complexes is due to the increased solubility of the MLT:CD complexes.

  19. OptiPrep? Density Gradient Solutions for Macromolecules and Macromolecular Complexes

    Directory of Open Access Journals (Sweden)

    John Graham

    2002-01-01

    Full Text Available Any density gradient for the isolation of mammalian cells should ideally only expose the sedimenting particles to an increasing concentration of the gradient solute. Thus they will experience only an increasing density and viscosity, other parameters such as osmolality, pH, ionic strength and the concentration of important additives (such as EDTA or divalent cations should remain as close to constant as possible. This Protocol Article describes the strategies for the dilution of OptiPrep™ in order to prepare such solutions for mammalian cells.

  20. On the binding affinity of macromolecular complexes : daring to ask why proteins interact

    NARCIS (Netherlands)

    Kastritis, P.

    2012-01-01

    The last twenty years we have reached the conclusion that most of the cellular functions are orchestrated by interacting protein molecules. It has also become clear that modifying or preventing these protein-protein interactions may have great therapeutic potential, especially for curing diseases

  1. The Postgraduate Study of Macromolecular Sciences at the University of Zagreb (1971-1980

    Directory of Open Access Journals (Sweden)

    Kunst, B.

    2008-07-01

    Full Text Available The postgraduate study of macromolecular sciences (PSMS was established at the University of Zagreb in 1971 as a university study in the time of expressed interdisciplinary permeation of natural sciences - physics, chemistry and biology, and application of their achievements in technologicaldisciplines. PSMS was established by a group of prominent university professors from the schools of Science, Chemical Technology, Pharmacy and Medicine, as well as from the Institute of Biology. The study comprised basic fields of macromolecular sciences: organic chemistry of synthetic macromolecules, physical chemistry of macromolecules, physics of macromolecules, biological macromolecules and polymer engineering with polymer application and processing, and teaching was performed in 29 lecture courses lead by 30 professors with their collaborators. PSMS ceased to exist with the change of legislation in Croatia in 1980, when the attitude prevailed to render back postgraduate studies to the university schools. During 9 years of existence of PSMS the MSci grade was awarded to 37 macromolecular experts. It was assessed that the PSMS some thirty years ago was an important example of modern postgraduate education as compared with the international postgraduate development. In concordance with the recent introduction of similar interdisciplinary studies in macromolecular sciences elsewhere in the world, the establishment of a modern interdisciplinary study in the field would be of importance for further development of these sciences in Croatia.

  2. Synthesis and characterization of macromolecular rhodamine tethers and their interactions with P-glycoprotein.

    Science.gov (United States)

    Crawford, Lindsey; Putnam, David

    2014-08-20

    Rhodamine dyes are well-known P-glycoprotein (P-gp) substrates that have played an important role in the detection of inhibitors and other substrates of P-gp, as well as in the understanding of P-gp function. Macromolecular conjugates of rhodamines could prove useful as tethers for further probing of P-gp structure and function. Two macromolecular derivatives of rhodamine, methoxypolyethylene glycol-rhodamine6G and methoxypolyethylene glycol-rhodamine123, were synthesized through the 2'-position of rhodamine6G and rhodamine123, thoroughly characterized, and then evaluated by inhibition with verapamil for their ability to interact with P-gp and to act as efflux substrates. To put the results into context, the P-gp interactions of the new conjugates were compared to the commercially available methoxypolyethylene glycol-rhodamineB. FACS analysis confirmed that macromolecular tethers of rhodamine6G, rhodamine123, and rhodamineB were accumulated in P-gp expressing cells 5.2 ± 0.3%, 26.2 ± 4%, and 64.2 ± 6%, respectively, compared to a sensitive cell line that does not overexpress P-gp. Along with confocal imaging, the efflux analysis confirmed that the macromolecular rhodamine tethers remain P-gp substrates. These results open potential avenues for new ways to probe the function of P-gp both in vitro and in vivo.

  3. Interplay between the bacterial nucleoid protein H-NS and macromolecular crowding in compacting DNA

    NARCIS (Netherlands)

    Wintraecken, C.H.J.M.

    2012-01-01

    In this dissertation we discuss H-NS and its connection to nucleoid compaction and organization. Nucleoid formation involves a dramatic reduction in coil volume of the genomic DNA. Four factors are thought to influence coil volume: supercoiling, DNA charge neutralization, macromolecular

  4. Effect of macromolecular crowding on the rate of diffusion-limited ...

    Indian Academy of Sciences (India)

    The enzymatic reaction rate has been shown to be affected by the presence of such macromolecules. A simple numerical model is proposed here based on percolation and diffusion in disordered systems to study the effect of macromolecular crowding on the enzymatic reaction rates. The model qualitatively explains some ...

  5. Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

    Czech Academy of Sciences Publication Activity Database

    Kissel, M.; Peschke, P.; Šubr, Vladimír; Ulbrich, Karel; Strunz, A. M.; Kühnlein, R.; Debus, J.; Friedrich, E.

    2002-01-01

    Roč. 29, č. 8 (2002), s. 1055-1062 ISSN 1619-7070 R&D Projects: GA ČR GV307/96/K226 Institutional research plan: CEZ:AV0Z4050913 Keywords : EPR effect * Radiolabelled macromolecules * Pharmacokinetic Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.568, year: 2002

  6. Thermodynamics of Macromolecular Association in Heterogeneous Crowding Environments: Theoretical and Simulation Studies with a Simplified Model.

    Science.gov (United States)

    Ando, Tadashi; Yu, Isseki; Feig, Michael; Sugita, Yuji

    2016-11-23

    The cytoplasm of a cell is crowded with many different kinds of macromolecules. The macromolecular crowding affects the thermodynamics and kinetics of biological reactions in a living cell, such as protein folding, association, and diffusion. Theoretical and simulation studies using simplified models focus on the essential features of the crowding effects and provide a basis for analyzing experimental data. In most of the previous studies on the crowding effects, a uniform crowder size is assumed, which is in contrast to the inhomogeneous size distribution of macromolecules in a living cell. Here, we evaluate the free energy changes upon macromolecular association in a cell-like inhomogeneous crowding system via a theory of hard-sphere fluids and free energy calculations using Brownian dynamics trajectories. The inhomogeneous crowding model based on 41 different types of macromolecules represented by spheres with different radii mimics the physiological concentrations of macromolecules in the cytoplasm of Mycoplasma genitalium. The free energy changes of macromolecular association evaluated by the theory and simulations were in good agreement with each other. The crowder size distribution affects both specific and nonspecific molecular associations, suggesting that not only the volume fraction but also the size distribution of macromolecules are important factors for evaluating in vivo crowding effects. This study relates in vitro experiments on macromolecular crowding to in vivo crowding effects by using the theory of hard-sphere fluids with crowder-size heterogeneity.

  7. Alternating ring-opening copolymerization of cyclohexene oxide with phthalic anhydride catalyzed by iron(III) salen complexes

    Czech Academy of Sciences Publication Activity Database

    Mundil, R.; Hošťálek, Z.; Šeděnková, Ivana; Merna, J.

    2015-01-01

    Roč. 23, č. 2 (2015), s. 161-166 ISSN 1598-5032 Institutional support: RVO:61389013 Keywords : polyesters * iron salen complexes * catalysis Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.357, year: 2015

  8. Solubility profiles, hydration and desolvation of curcumin complexed with γ-cyclodextrin and hydroxypropyl-γ-cyclodextrin

    Science.gov (United States)

    Shityakov, Sergey; Salmas, Ramin Ekhteiari; Durdagi, Serdar; Roewer, Norbert; Förster, Carola; Broscheit, Jens

    2017-04-01

    In this study, we investigated curcumin (CUR) solubility profiles and hydration/desolvation effects of this substance formulated with γ-cyclodextrin (γ-CD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD) excipients. The CUR/HP-γ-CD complex was found to be more stable in solution with the highest apparent stability constant for CUR/HP-γ-CD (Kc = 1.58*104 M-1) as the more soluble form in distilled water. The in silico calculations, including molecular docking, Monte Carlo (MC), and molecular dynamics (MD) simulations, indicated that water molecules play an important role in host-guest complexation mediating the CUR binding to cyclodextrins via hydrogen bond formations. The CUR hydration/desolvation effects contributed to the complex formation by elevating the CUR binding affinity to both CDs. The CUR/HP-γ-CD complex after the CUR hydration was determined with a minimal Gibbs free energy of binding (ΔGbind = -9.93 kcal*mol-1) due to the major hydrophobic (vdW) forces. Overall, the results of this study can aid a development of cyclodextrin-based drug delivery vectors, signifying the importance of water molecules during the formulation processes.

  9. Synthesis and Crystal Structures of Two Metal Complexes Incorporating Malonate and Organodiamine Ligands

    International Nuclear Information System (INIS)

    Zhang, Quan Zheng; Yang, Wen Bin; Chen, Shu Mei; Lu, Can Zhong

    2005-01-01

    In the present work we report the synthesis and X-ray crystal structures of two new malonato complexes incorporating organodiamine ligands: [Ni(phen)(mal)(H_2O)_2]·3H_2O (H_2mal = malonic acid, phen = 1,10-phenanthroline) and [Zn(bpy)(H_2O)]_2[Zn(bpy)(mal)(H_2O)_2]_2(NO_3)_4·4H_2O (bpy = 2,2'-bipyridine). Investigation on novel organic-inorganic hybrid framework assemblies represents one of the most active areas of material science and chemical research. Major advances have been made in these materials due to their interesting properties and potential in various applications, e. g., electrical conductivity, magnetism, host-guest chemistry, ion exchange, catalysis, nonlinear optics, etc. Moreover, discovery and design of such new materials with specific networks remain of a particularly important and active subject in the field of supramolecuar chemistry and crystal engineering. A variety of complexes with interesting compositions and topologies have been prepared through taking certain factors into account, such as the coordination nature of the metal ion and the shape, functionality, flexibility, and symmetry of organic ligand. Recently, some dicarboxylate ligands, such as oxalate, malonate, and terephthalate, have been widely used in the construction of these interesting structures

  10. Direct Synthesis of Polymer Nanotubes by Aqueous Dispersion Polymerization of a Cyclodextrin/Styrene Complex.

    Science.gov (United States)

    Chen, Xi; Liu, Lei; Huo, Meng; Zeng, Min; Peng, Liao; Feng, Anchao; Wang, Xiaosong; Yuan, Jinying

    2017-12-22

    A one-step synthesis of nanotubes by RAFT dispersion polymerization of cyclodextrin/styrene (CD/St) complexes directly in water is presented. The resulted amphiphilic PEG-b-PS diblock copolymers self-assemble in situ into nanoparticles with various morphologies. Spheres, worms, lamellae, and nanotubes were controllably obtained. Because of the complexation, the swelling degree of polystyrene (PS) blocks by free St is limited, resulting in limited mobility of PS chains. Consequently, kinetically trapped lamellae and nanotubes were obtained instead of spherical vesicles. During the formation of nanotubes, small vesicles first formed at the ends of the tape-like lamellae, then grew and fused into nanotubes with a limited chain rearrangement. The introduction of a host-guest interaction based on CDs enables the aqueous dispersion polymerization of water-immiscible monomers, and produces kinetically trapped nanostructures, which could be a powerful technique for nanomaterials synthesis. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Flexibility damps macromolecular crowding effects on protein folding dynamics: Application to the murine prion protein (121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2014-01-01

    A model of protein folding kinetics is applied to study the combined effects of protein flexibility and macromolecular crowding on protein folding rate and stability. It is found that the increase in stability and folding rate promoted by macromolecular crowding is damped for proteins with highly flexible native structures. The model is applied to the folding dynamics of the murine prion protein (121-231). It is found that the high flexibility of the native isoform of the murine prion protein (121-231) reduces the effects of macromolecular crowding on its folding dynamics. The relevance of these findings for the pathogenic mechanism are discussed.

  12. Surface and permeability properties of membranes from polyelectrolyte complexes and polyelectrolyte surfactant complexes

    Czech Academy of Sciences Publication Activity Database

    Schwarz, H. H.; Lukáš, Jaromír; Richau, K.

    2003-01-01

    Roč. 218, 1-2 (2003), s. 1-9 ISSN 0376-7388 R&D Projects: GA AV ČR KSK4050111 Keywords : polyelectrolyte complex membranes * pervaporation * dehydration of organics Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.081, year: 2003

  13. Block copolymer libraries: modular versatility of the macromolecular Lego system.

    Science.gov (United States)

    Lohmeijer, Bas G G; Wouters, Daan; Yin, Zhihui; Schubert, Ulrich S

    2004-12-21

    The synthesis and characterization of a new 4 x 4 library of block copolymers based on polystyrene and poly(ethylene oxide) connected by an asymmetrical octahedral bis(terpyridine) ruthenium complex at the block junction are described, while initial studies on the thin film morphology of the components of the library are presented by the use of Atomic Force Microscopy, demonstrating the impact of a library approach to derive structure-property relationships.

  14. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    International Nuclear Information System (INIS)

    Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L.; Armour, Wes; Waterman, David G.; Iwata, So; Evans, Gwyndaf

    2013-01-01

    A systematic approach to the scaling and merging of data from multiple crystals in macromolecular crystallography is introduced and explained. The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein

  15. Macromolecularly crowded in vitro microenvironments accelerate the production of extracellular matrix-rich supramolecular assemblies.

    Science.gov (United States)

    Kumar, Pramod; Satyam, Abhigyan; Fan, Xingliang; Collin, Estelle; Rochev, Yury; Rodriguez, Brian J; Gorelov, Alexander; Dillon, Simon; Joshi, Lokesh; Raghunath, Michael; Pandit, Abhay; Zeugolis, Dimitrios I

    2015-03-04

    Therapeutic strategies based on the principles of tissue engineering by self-assembly put forward the notion that functional regeneration can be achieved by utilising the inherent capacity of cells to create highly sophisticated supramolecular assemblies. However, in dilute ex vivo microenvironments, prolonged culture time is required to develop an extracellular matrix-rich implantable device. Herein, we assessed the influence of macromolecular crowding, a biophysical phenomenon that regulates intra- and extra-cellular activities in multicellular organisms, in human corneal fibroblast culture. In the presence of macromolecules, abundant extracellular matrix deposition was evidenced as fast as 48 h in culture, even at low serum concentration. Temperature responsive copolymers allowed the detachment of dense and cohesive supramolecularly assembled living substitutes within 6 days in culture. Morphological, histological, gene and protein analysis assays demonstrated maintenance of tissue-specific function. Macromolecular crowding opens new avenues for a more rational design in engineering of clinically relevant tissue modules in vitro.

  16. Atomic force microscopy applied to study macromolecular content of embedded biological material

    Energy Technology Data Exchange (ETDEWEB)

    Matsko, Nadejda B. [Electron Microscopy Centre, Institute of Applied Physics, HPM C 15.1, ETH-Hoenggerberg, CH-8093, Zurich (Switzerland)]. E-mail: matsko@iap.phys.ethz.ch

    2007-02-15

    We demonstrate that atomic force microscopy represents a powerful tool for the estimation of structural preservation of biological samples embedded in epoxy resin, in terms of their macromolecular distribution and architecture. The comparison of atomic force microscopy (AFM) and transmission electron microscopy (TEM) images of a biosample (Caenorhabditis elegans) prepared following to different types of freeze-substitution protocols (conventional OsO{sub 4} fixation, epoxy fixation) led to the conclusion that high TEM stainability of the sample results from a low macromolecular density of the cellular matrix. We propose a novel procedure aimed to obtain AFM and TEM images of the same particular organelle, which strongly facilitates AFM image interpretation and reveals new ultrastructural aspects (mainly protein arrangement) of a biosample in addition to TEM data.

  17. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Foadi, James [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Aller, Pierre [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Alguel, Yilmaz; Cameron, Alex [Imperial College, London SW7 2AZ (United Kingdom); Axford, Danny; Owen, Robin L. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Armour, Wes [Oxford e-Research Centre (OeRC), Keble Road, Oxford OX1 3QG (United Kingdom); Waterman, David G. [Research Complex at Harwell (RCaH), Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0FA (United Kingdom); Iwata, So [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Evans, Gwyndaf, E-mail: gwyndaf.evans@diamond.ac.uk [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

    2013-08-01

    A systematic approach to the scaling and merging of data from multiple crystals in macromolecular crystallography is introduced and explained. The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein.

  18. Pi sampling: a methodical and flexible approach to initial macromolecular crystallization screening

    International Nuclear Information System (INIS)

    Gorrec, Fabrice; Palmer, Colin M.; Lebon, Guillaume; Warne, Tony

    2011-01-01

    Pi sampling, derived from the incomplete factorial approach, is an effort to maximize the diversity of macromolecular crystallization conditions and to facilitate the preparation of 96-condition initial screens. The Pi sampling method is derived from the incomplete factorial approach to macromolecular crystallization screen design. The resulting ‘Pi screens’ have a modular distribution of a given set of up to 36 stock solutions. Maximally diverse conditions can be produced by taking into account the properties of the chemicals used in the formulation and the concentrations of the corresponding solutions. The Pi sampling method has been implemented in a web-based application that generates screen formulations and recipes. It is particularly adapted to screens consisting of 96 different conditions. The flexibility and efficiency of Pi sampling is demonstrated by the crystallization of soluble proteins and of an integral membrane-protein sample

  19. Macromolecular Engineering: New Routes Towards the Synthesis of Well-??Defined Polyethers/Polyesters Co/Terpolymers with Different Architectures

    KAUST Repository

    Alamri, Haleema

    2016-01-01

    Macromolecular engineering (as discussed in the first chapter) of homo/copolymers refers to the specific tailoring of these materials for achieving an easy and reproducible synthesis that results in precise molecular

  20. The Postgraduate Study of Macromolecular Sciences at the University of Zagreb (1971-1980)

    OpenAIRE

    Kunst, B.; Dezelic, D.; Veksli, Z.

    2008-01-01

    The postgraduate study of macromolecular sciences (PSMS) was established at the University of Zagreb in 1971 as a university study in the time of expressed interdisciplinary permeation of natural sciences - physics, chemistry and biology, and application of their achievements in technologicaldisciplines. PSMS was established by a group of prominent university professors from the schools of Science, Chemical Technology, Pharmacy and Medicine, as well as from the Institute of Biology. The study...

  1. The Postgraduate Study of Macromolecular Sciences at the University of Zagreb (1971– 1980)

    OpenAIRE

    Deželić, D.; Kunst, B.; Veksli, Zorica

    2008-01-01

    The postgraduate study of macromolecular sciences (PSMS) was established at the University of Zagreb in 1971 as a university study in the time of expressed interdisciplinary permeation of natural sciences - physics, chemistry and biology, and application of their achievements in technological disciplines. PSMS was established by a group of prominent university professors from the schools of Science, Chemical Technology, Pharmacy and Medicine, as well as from the Institute of Biology. The s...

  2. Measurement and Interpretation of Diffuse Scattering in X-Ray Diffraction for Macromolecular Crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Wall, Michael E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-16

    X-ray diffraction from macromolecular crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering reflects the mean electron density in the unit cells of the crystal. The diffuse scattering arises from correlations in the variations of electron density that may occur from one unit cell to another, and therefore contains information about collective motions in proteins.

  3. Fully automated data collection and processing system on macromolecular crystallography beamlines at the PF

    International Nuclear Information System (INIS)

    Yamada, Yusuke; Hiraki, Masahiko; Matsugaki, Naohiro; Chavas, Leonard M.G.; Igarashi, Noriyuki; Wakatsuki, Soichi

    2012-01-01

    Fully automated data collection and processing system has been developed on macromolecular crystallography beamlines at the Photon Factory. In this system, the sample exchange, centering and data collection are sequentially performed for all samples stored in the sample exchange system at a beamline without any manual operations. Data processing of collected data sets is also performed automatically. These results are stored into the database system, and users can monitor the progress and results of automated experiment via a Web browser. (author)

  4. Macromolecular shape and interactions in layer-by-layer assemblies within cylindrical nanopores.

    Science.gov (United States)

    Lazzara, Thomas D; Lau, K H Aaron; Knoll, Wolfgang; Janshoff, Andreas; Steinem, Claudia

    2012-01-01

    Layer-by-layer (LbL) deposition of polyelectrolytes and proteins within the cylindrical nanopores of anodic aluminum oxide (AAO) membranes was studied by optical waveguide spectroscopy (OWS). AAO has aligned cylindrical, nonintersecting pores with a defined pore diameter d(0) and functions as a planar optical waveguide so as to monitor, in situ, the LbL process by OWS. The LbL deposition of globular proteins, i.e., avidin and biotinylated bovine serum albumin was compared with that of linear polyelectrolytes (linear-PEs), both species being of similar molecular weight. LbL deposition within the cylindrical AAO geometry for different pore diameters (d(0) = 25-80 nm) for the various macromolecular species, showed that the multilayer film growth was inhibited at different maximum numbers of LbL steps (n(max)). The value of n(max) was greatest for linear-PEs, while proteins had a lower value. The cylindrical pore geometry imposes a physical limit to LbL growth such that n(max) is strongly dependent on the overall internal structure of the LbL film. For all macromolecular species, deposition was inhibited in native AAO, having pores of d(0) = 25-30 nm. Both, OWS and scanning electron microscopy showed that LbL growth in larger AAO pores (d(0) > 25-30 nm) became inhibited when approaching a pore diameter of d(eff,n_max) = 25-35 nm, a similar size to that of native AAO pores, with d(0) = 25-30 nm. For a reasonable estimation of d(eff,n_max), the actual volume occupied by a macromolecular assembly must be taken into consideration. The results clearly show that electrostatic LbL allowed for compact macromolecular layers, whereas proteins formed loosely packed multilayers.

  5. Macromolecular structure determination in the post-genome era

    CERN Document Server

    Kuhn, P

    2001-01-01

    Recent advances in genetics, molecular biology and crystallographic instrumentation and methodology have led to a revolution in the field of Structural Molecular Biology (SMB). These combined advances have paved the way to a more complete and detailed understanding of the biological macromolecules that make up an organism, both in terms of their individual functions and also the interactions between them. In this paper we describe a large-scale, genomic approach to the three-dimensional structure determination of macromolecules and their complexes, using high-throughput methodology to streamline all aspects of the process. This task requires the development of automated high-intensity synchrotron beam lines for X-ray diffraction data collection from single crystal samples. Furthermore, these beam lines must be operated within a sophisticated software and hardware environment, which is capable of delivering a completely automated structure determination pipeline. The SMB resource at SSRL is developing a system...

  6. Tuning the properties of an anthracene-based PPE-PPV copolymer by fine variation of its macromolecular parameters

    Czech Academy of Sciences Publication Activity Database

    Tinti, F.; Sabir, F. K.; Gazzano, M.; Righi, S.; Ulbricht, C.; Usluer, Ö.; Pokorná, Veronika; Cimrová, Věra; Yohannes, T.; Egbe, D. A. M.; Camaioni, N.

    2013-01-01

    Roč. 3, č. 19 (2013), s. 6972-6980 ISSN 2046-2069 R&D Projects: GA ČR GAP106/12/0827; GA ČR(CZ) GA13-26542S Institutional support: RVO:61389013 Keywords : anthracene-containing PPE-PPV copolymer * macromolecular parameters * structural and transport properties Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.708, year: 2013

  7. Macromolecular diffusion in crowded media beyond the hard-sphere model.

    Science.gov (United States)

    Blanco, Pablo M; Garcés, Josep Lluís; Madurga, Sergio; Mas, Francesc

    2018-04-25

    The effect of macromolecular crowding on diffusion beyond the hard-core sphere model is studied. A new coarse-grained model is presented, the Chain Entanglement Softened Potential (CESP) model, which takes into account the macromolecular flexibility and chain entanglement. The CESP model uses a shoulder-shaped interaction potential that is implemented in the Brownian Dynamics (BD) computations. The interaction potential contains only one parameter associated with the chain entanglement energetic cost (Ur). The hydrodynamic interactions are included in the BD computations via Tokuyama mean-field equations. The model is used to analyze the diffusion of a streptavidin protein among different sized dextran obstacles. For this system, Ur is obtained by fitting the streptavidin experimental long-time diffusion coefficient Dlongversus the macromolecular concentration for D50 (indicating their molecular weight in kg mol-1) dextran obstacles. The obtained Dlong values show better quantitative agreement with experiments than those obtained with hard-core spheres. Moreover, once parametrized, the CESP model is also able to quantitatively predict Dlong and the anomalous exponent (α) for streptavidin diffusion among D10, D400 and D700 dextran obstacles. Dlong, the short-time diffusion coefficient (Dshort) and α are obtained from the BD simulations by using a new empirical expression, able to describe the full temporal evolution of the diffusion coefficient.

  8. Homogenization Theory for the Prediction of Obstructed Solute Diffusivity in Macromolecular Solutions.

    Science.gov (United States)

    Donovan, Preston; Chehreghanianzabi, Yasaman; Rathinam, Muruhan; Zustiak, Silviya Petrova

    2016-01-01

    The study of diffusion in macromolecular solutions is important in many biomedical applications such as separations, drug delivery, and cell encapsulation, and key for many biological processes such as protein assembly and interstitial transport. Not surprisingly, multiple models for the a-priori prediction of diffusion in macromolecular environments have been proposed. However, most models include parameters that are not readily measurable, are specific to the polymer-solute-solvent system, or are fitted and do not have a physical meaning. Here, for the first time, we develop a homogenization theory framework for the prediction of effective solute diffusivity in macromolecular environments based on physical parameters that are easily measurable and not specific to the macromolecule-solute-solvent system. Homogenization theory is useful for situations where knowledge of fine-scale parameters is used to predict bulk system behavior. As a first approximation, we focus on a model where the solute is subjected to obstructed diffusion via stationary spherical obstacles. We find that the homogenization theory results agree well with computationally more expensive Monte Carlo simulations. Moreover, the homogenization theory agrees with effective diffusivities of a solute in dilute and semi-dilute polymer solutions measured using fluorescence correlation spectroscopy. Lastly, we provide a mathematical formula for the effective diffusivity in terms of a non-dimensional and easily measurable geometric system parameter.

  9. Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics.

    Science.gov (United States)

    Maximova, Tatiana; Moffatt, Ryan; Ma, Buyong; Nussinov, Ruth; Shehu, Amarda

    2016-04-01

    Investigation of macromolecular structure and dynamics is fundamental to understanding how macromolecules carry out their functions in the cell. Significant advances have been made toward this end in silico, with a growing number of computational methods proposed yearly to study and simulate various aspects of macromolecular structure and dynamics. This review aims to provide an overview of recent advances, focusing primarily on methods proposed for exploring the structure space of macromolecules in isolation and in assemblies for the purpose of characterizing equilibrium structure and dynamics. In addition to surveying recent applications that showcase current capabilities of computational methods, this review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules. This review is not meant to be exhaustive, as such an endeavor is impossible, but rather aims to balance breadth and depth of strategies for modeling macromolecular structure and dynamics for a broad audience of novices and experts.

  10. In Vitro and In Vivo Evaluation of Microparticulate Drug Delivery Systems Composed of Macromolecular Prodrugs

    Directory of Open Access Journals (Sweden)

    Yoshiharu Machida

    2008-08-01

    Full Text Available Macromolecular prodrugs are very useful systems for achieving controlled drug release and drug targeting. In particular, various macromolecule-antitumor drug conjugates enhance the effectiveness and improve the toxic side effects. Also, polymeric micro- and nanoparticles have been actively examined and their in vivo behaviors elucidated, and it has been realized that their particle characteristics are very useful to control drug behavior. Recently, researches based on the combination of the concepts of macromolecular prodrugs and micro- or nanoparticles have been reported, although they are limited. Macromolecular prodrugs enable drugs to be released at a certain controlled release rate based on the features of the macromolecule-drug linkage. Micro- and nanoparticles can control in vivo behavior based on their size, surface charge and surface structure. These merits are expected for systems produced by the combination of each concept. In this review, several micro- or nanoparticles composed of macromolecule-drug conjugates are described for their preparation, in vitro properties and/or in vivo behavior.

  11. Homogenization Theory for the Prediction of Obstructed Solute Diffusivity in Macromolecular Solutions.

    Directory of Open Access Journals (Sweden)

    Preston Donovan

    Full Text Available The study of diffusion in macromolecular solutions is important in many biomedical applications such as separations, drug delivery, and cell encapsulation, and key for many biological processes such as protein assembly and interstitial transport. Not surprisingly, multiple models for the a-priori prediction of diffusion in macromolecular environments have been proposed. However, most models include parameters that are not readily measurable, are specific to the polymer-solute-solvent system, or are fitted and do not have a physical meaning. Here, for the first time, we develop a homogenization theory framework for the prediction of effective solute diffusivity in macromolecular environments based on physical parameters that are easily measurable and not specific to the macromolecule-solute-solvent system. Homogenization theory is useful for situations where knowledge of fine-scale parameters is used to predict bulk system behavior. As a first approximation, we focus on a model where the solute is subjected to obstructed diffusion via stationary spherical obstacles. We find that the homogenization theory results agree well with computationally more expensive Monte Carlo simulations. Moreover, the homogenization theory agrees with effective diffusivities of a solute in dilute and semi-dilute polymer solutions measured using fluorescence correlation spectroscopy. Lastly, we provide a mathematical formula for the effective diffusivity in terms of a non-dimensional and easily measurable geometric system parameter.

  12. MxCuBE: a synchrotron beamline control environment customized for macromolecular crystallography experiments

    International Nuclear Information System (INIS)

    Gabadinho, José; Beteva, Antonia; Guijarro, Matias; Rey-Bakaikoa, Vicente; Spruce, Darren

    2010-01-01

    MxCuBE is a beamline control environment optimized for the needs of macromolecular crystallography. This paper describes the design of the software and the features that MxCuBE currently provides. The design and features of a beamline control software system for macromolecular crystallography (MX) experiments developed at the European Synchrotron Radiation Facility (ESRF) are described. This system, MxCuBE, allows users to easily and simply interact with beamline hardware components and provides automated routines for common tasks in the operation of a synchrotron beamline dedicated to experiments in MX. Additional functionality is provided through intuitive interfaces that enable the assessment of the diffraction characteristics of samples, experiment planning, automatic data collection and the on-line collection and analysis of X-ray emission spectra. The software can be run in a tandem client-server mode that allows for remote control and relevant experimental parameters and results are automatically logged in a relational database, ISPyB. MxCuBE is modular, flexible and extensible and is currently deployed on eight macromolecular crystallography beamlines at the ESRF. Additionally, the software is installed at MAX-lab beamline I911-3 and at BESSY beamline BL14.1

  13. A smooth and differentiable bulk-solvent model for macromolecular diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Fenn, T. D. [Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford, California (United States); Schnieders, M. J. [Department of Chemistry, Stanford, California (United States); Brunger, A. T., E-mail: brunger@stanford.edu [Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford, California (United States); Departments of Neurology and Neurological Sciences, Structural Biology and Photon Science, Stanford, California (United States)

    2010-09-01

    A new method for modeling the bulk solvent in macromolecular diffraction data based on Babinet’s principle is presented. The proposed models offer the advantage of differentiability with respect to atomic coordinates. Inclusion of low-resolution data in macromolecular crystallography requires a model for the bulk solvent. Previous methods have used a binary mask to accomplish this, which has proven to be very effective, but the mask is discontinuous at the solute–solvent boundary (i.e. the mask value jumps from zero to one) and is not differentiable with respect to atomic parameters. Here, two algorithms are introduced for computing bulk-solvent models using either a polynomial switch or a smoothly thresholded product of Gaussians, and both models are shown to be efficient and differentiable with respect to atomic coordinates. These alternative bulk-solvent models offer algorithmic improvements, while showing similar agreement of the model with the observed amplitudes relative to the binary model as monitored using R, R{sub free} and differences between experimental and model phases. As with the standard solvent models, the alternative models improve the agreement primarily with lower resolution (>6 Å) data versus no bulk solvent. The models are easily implemented into crystallographic software packages and can be used as a general method for bulk-solvent correction in macromolecular crystallography.

  14. A smooth and differentiable bulk-solvent model for macromolecular diffraction

    International Nuclear Information System (INIS)

    Fenn, T. D.; Schnieders, M. J.; Brunger, A. T.

    2010-01-01

    A new method for modeling the bulk solvent in macromolecular diffraction data based on Babinet’s principle is presented. The proposed models offer the advantage of differentiability with respect to atomic coordinates. Inclusion of low-resolution data in macromolecular crystallography requires a model for the bulk solvent. Previous methods have used a binary mask to accomplish this, which has proven to be very effective, but the mask is discontinuous at the solute–solvent boundary (i.e. the mask value jumps from zero to one) and is not differentiable with respect to atomic parameters. Here, two algorithms are introduced for computing bulk-solvent models using either a polynomial switch or a smoothly thresholded product of Gaussians, and both models are shown to be efficient and differentiable with respect to atomic coordinates. These alternative bulk-solvent models offer algorithmic improvements, while showing similar agreement of the model with the observed amplitudes relative to the binary model as monitored using R, R free and differences between experimental and model phases. As with the standard solvent models, the alternative models improve the agreement primarily with lower resolution (>6 Å) data versus no bulk solvent. The models are easily implemented into crystallographic software packages and can be used as a general method for bulk-solvent correction in macromolecular crystallography

  15. Gaussian-Based Smooth Dielectric Function: A Surface-Free Approach for Modeling Macromolecular Binding in Solvents

    Directory of Open Access Journals (Sweden)

    Arghya Chakravorty

    2018-03-01

    Full Text Available Conventional modeling techniques to model macromolecular solvation and its effect on binding in the framework of Poisson-Boltzmann based implicit solvent models make use of a geometrically defined surface to depict the separation of macromolecular interior (low dielectric constant from the solvent phase (high dielectric constant. Though this simplification saves time and computational resources without significantly compromising the accuracy of free energy calculations, it bypasses some of the key physio-chemical properties of the solute-solvent interface, e.g., the altered flexibility of water molecules and that of side chains at the interface, which results in dielectric properties different from both bulk water and macromolecular interior, respectively. Here we present a Gaussian-based smooth dielectric model, an inhomogeneous dielectric distribution model that mimics the effect of macromolecular flexibility and captures the altered properties of surface bound water molecules. Thus, the model delivers a smooth transition of dielectric properties from the macromolecular interior to the solvent phase, eliminating any unphysical surface separating the two phases. Using various examples of macromolecular binding, we demonstrate its utility and illustrate the comparison with the conventional 2-dielectric model. We also showcase some additional abilities of this model, viz. to account for the effect of electrolytes in the solution and to render the distribution profile of water across a lipid membrane.

  16. Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.

    Science.gov (United States)

    Kaneshiro, Todd L; Ke, Tianyi; Jeong, Eun-Kee; Parker, Dennis L; Lu, Zheng-Rong

    2006-06-01

    The purpose of this study was to synthesize biodegradable Gd-DTPA L-cystine bisamide copolymers (GCAC) as safe and effective, macromolecular contrast agents for magnetic resonance imaging (MRI) and to evaluate their biodegradability and efficacy in MR blood pool imaging in an animal model. Three new biodegradable GCAC with different substituents at the cystine bisamide [R = H (GCAC), CH2CH2CH3 (Gd-DTPA L-cystine bispropyl amide copolymers, GCPC), and CH(CH3)2 (Gd-DTPA cystine bisisopropyl copolymers, GCIC)] were prepared by the condensation copolymerization of diethylenetriamine pentaacetic acid (DTPA) dianhydride with cystine bisamide or bisalkyl amides, followed by complexation with gadolinium triacetate. The degradability of the agents was studied in vitro by incubation in 15 microM cysteine and in vivo with Sprague-Dawley rats. The kinetics of in vivo contrast enhancement was investigated in Sprague-Dawley rats on a Siemens Trio 3 T scanner. The apparent molecular weight of the polydisulfide Gd(III) chelates ranged from 22 to 25 kDa. The longitudinal (T1) relaxivities of GCAC, GCPC, and GCIC were 4.37, 5.28, and 5.56 mM(-1) s(-1) at 3 T, respectively. The polymeric ligands and polymeric Gd(III) chelates readily degraded into smaller molecules in incubation with 15 microM cysteine via disulfide-thiol exchange reactions. The in vitro degradation rates of both the polymeric ligands and macromolecular Gd(III) chelates decreased as the steric effect around the disulfide bonds increased. The agents readily degraded in vivo, and the catabolic degradation products were detected in rat urine samples collected after intravenous injection. The agents showed strong contrast enhancement in the blood pool, major organs, and tissues at a dose of 0.1 mmol Gd/kg. The difference of their in vitro degradability did not significantly alter the kinetics of in vivo contrast enhancement of the agents. These novel GCAC are promising contrast agents for cardiovascular and tumor MRI

  17. Supramolecular Assembly of Comb-like Macromolecules Induced by Chemical Reactions that Modulate the Macromolecular Interactions In Situ.

    Science.gov (United States)

    Xia, Hongwei; Fu, Hailin; Zhang, Yanfeng; Shih, Kuo-Chih; Ren, Yuan; Anuganti, Murali; Nieh, Mu-Ping; Cheng, Jianjun; Lin, Yao

    2017-08-16

    Supramolecular polymerization or assembly of proteins or large macromolecular units by a homogeneous nucleation mechanism can be quite slow and require specific solution conditions. In nature, protein assembly is often regulated by molecules that modulate the electrostatic interactions of the protein subunits for various association strengths. The key to this regulation is the coupling of the assembly process with a reversible or irreversible chemical reaction that occurs within the constituent subunits. However, realizing this complex process by the rational design of synthetic molecules or macromolecules remains a challenge. Herein, we use a synthetic polypeptide-grafted comb macromolecule to demonstrate how the in situ modulation of interactions between the charged macromolecules affects their resulting supramolecular structures. The kinetics of structural formation was studied and can be described by a generalized model of nucleated polymerization containing secondary pathways. Basic thermodynamic analysis indicated the delicate role of the electrostatic interactions between the charged subunits in the reaction-induced assembly process. This approach may be applicable for assembling a variety of ionic soft matters that are amenable to chemical reactions in situ.

  18. Electroplex emission from a layer of a mixture of a europium complex and tris(8-quinolinolato) aluminum

    Science.gov (United States)

    Cao, Hong; Gao, Xicun; Huang, Chun-Hui

    2000-07-01

    With a europium complex, tris(α-thenoyltrifluoroacetonato) bis(triphenylphosphine oxide) europium (Eu(TTA) 3(TPPO) 2), as the light-emitting layer, N, N'-diphenyl- N, N'-di( m-tolyl)-benzidine (TPD) as the hole transport layer and tris(8-quinolinolato) aluminum (ALQ) as the electron transport layer, the triple-layer electroluminescent (EL) device emits red light characteristic of Eu 3+ emission. However, as the mixture of Eu(TTA) 3(TPPO) 2 and ALQ is co-evaporated as the light-emitting layer to form a bilayer EL device, a new wide-banded emission peaked at c. 640 nm was obtained. This emission is neither from ALQ nor from the europium complex. The photoluminescence (PL) of the thin film on quartz substrate evaporated from one mixed solid powder of Eu(TTA) 3(TPPO) 2 and ALQ is composed of distinct PL emissions of Eu(TTA) 3(TPPO) 2 and ALQ, denying an exciplex formation mechanism. It is impossible to form a host-guest system. We propose that the EL emission peaked at c. 640 nm is from an electroplex route: a transition between the lowest unoccupied molecular orbital (LUMO) of Eu(TTA) 3(TPPO) 2 and the highest occupied molecular orbital (HOMO) of ALQ.

  19. Macromolecular structure determination in the post-genome era

    International Nuclear Information System (INIS)

    Kuhn, P.; Soltis, S.M.

    2001-01-01

    Recent advances in genetics, molecular biology and crystallographic instrumentation and methodology have led to a revolution in the field of Structural Molecular Biology (SMB). These combined advances have paved the way to a more complete and detailed understanding of the biological macromolecules that make up an organism, both in terms of their individual functions and also the interactions between them. In this paper we describe a large-scale, genomic approach to the three-dimensional structure determination of macromolecules and their complexes, using high-throughput methodology to streamline all aspects of the process. This task requires the development of automated high-intensity synchrotron beam lines for X-ray diffraction data collection from single crystal samples. Furthermore, these beam lines must be operated within a sophisticated software and hardware environment, which is capable of delivering a completely automated structure determination pipeline. The SMB resource at SSRL is developing a system for the structure determination steps of this process, starting with the initial characterization of the frozen sample, followed by data collection, data reduction, phase determination, and model building. This paper focuses on the data collection elements of this high-throughput system

  20. Polypeptoids: A perfect match for molecular definition and macromolecular engineering?

    KAUST Repository

    Luxenhofer, Robert

    2013-04-19

    Precision synthesis of polymers has been a hot topic in recent years. While this is notoriously difficult to address for polymers with a CC backbone, Merrifield has discovered a way many decades ago for polypeptides. Using a similar approach, N-substituted polypeptides, so-called polypeptoids have been synthesized and studied for about 20 years. In contrast, the living ring-opening polymerization (ROP) of N-substituted N-carboxyanhydrides was among the first living polymerizations to be discovered. More recently, a surge in new synthetic approaches led to the efficient synthesis of cyclic or linear multiblock copolypeptoids. Thus, polypeptoids can be synthesized either by solid phase synthesis to yield complex and exactly defined oligo- and small polymers or by ROP of appropriately N-substituted N-carboxyanhydrides (NNCA) to give linear, cyclic, or star-like polymers. Together with an excellent biocompatibility, this polymer family may have a bright future ahead as biomaterials. © 2013 Wiley Periodicals, Inc.

  1. Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

    Science.gov (United States)

    Wang, Jianxin Steven

    The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in

  2. Location of MTBE and toluene in the channel system of the zeolite mordenite: Adsorption and host-guest interactions

    Energy Technology Data Exchange (ETDEWEB)

    Arletti, Rossella, E-mail: rossella.arletti@unito.it [Department of Earth Sciences, University of Torino Via Valperga Caluso 35, I-10125, Torino (Italy); Martucci, Annalisa; Alberti, Alberto [Department of Earth Sciences, University of Ferrara, Via G. Saragat 1, I-44100, Ferrara (Italy); Pasti, Luisa; Nassi, Marianna [Department of Chemistry, University of Ferrara, Via L. Borsari 26, I-44100 Ferrara (Italy); Bagatin, Roberto [Research Centre for Non-Conventional Energy-Istituto ENI Donegani, Environmental Technologies, Via Fauser 4, I-28100 Novara (Italy)

    2012-10-15

    This paper reports a study of the location of Methyl Tertiary Butyl Ether (MTBE) and toluene molecules adsorbed in the pores of the organophylic zeolite mordenite from an aqueous solution. The presence of these organic molecules in the zeolite channels was revealed by structure refinement performed by the Rietveld method. About 3 molecules of MTBE and 3.6 molecules of toluene per unit cell were incorporated into the cavities of mordenite, representing 75% and 80% of the total absorption capacity of this zeolite. In both cases a water molecule was localized inside the side pocket of mordenite. The saturation capacity determined by the adsorption isotherms, obtained by batch experiments, and the weight loss given by thermogravimetric (TG) analyses were in very good agreement with these values. The interatomic distances obtained after the structural refinements suggest MTBE could be connected to the framework through a water molecule, while toluene could be bonded to framework oxygen atoms. The rapid and high adsorption of these hydrocarbons into the organophylic mordenite zeolite makes this cheap and environmental friendly material a suitable candidate for the removal of these pollutants from water. - graphical abstract: Location of MTBE (a) and toluene (b) in mordenite channels (projection along the [001] direction). Highlights: Black-Right-Pointing-Pointer We investigated the MTBE and toluene adsorption process into an organophilic zeolite mordenite. Black-Right-Pointing-Pointer The presence of MTBE and toluene in mordenite was determined by X-ray diffraction studies. Black-Right-Pointing-Pointer About 3 molecules of MTBE and 3.6 molecules of toluene per unit cell were incorporated into the zeolite cavities. Black-Right-Pointing-Pointer MTBE is connected to the framework through a water molecule. Black-Right-Pointing-Pointer Toluene is directly bonded to framework oxygen atoms.

  3. Three-Dimensional Energy Transport in Highly Luminescent Host-Guest Crystals: A Quantitative Experimental and Theoretical Study

    DEFF Research Database (Denmark)

    Poulsen, Lars; Jazdzyk, M; Communal, J.-E.

    2007-01-01

    process is modeled by a Monte Carlo approach including homo and hetero transfer steps with multi-acceptor distribution. In this dense system, the classical Förster point-dipole approach for energy transfer breaks down, and the hopping rates are therefore calculated on the basis of a quantum...

  4. Formation of hybrid gold nanoparticle network aggregates by specific host-guest interactions in a turbulent flow reactor

    NARCIS (Netherlands)

    Weinhart-Mejia, R.; Huskens, Jurriaan

    2014-01-01

    A multi-inlet vortex mixer (MIVM) was used to investigate the formation of hybrid gold nanoparticle network aggregates under highly turbulent flow conditions. To form aggregates, gold nanoparticles were functionalized with β-cyclodextrin (CD) and mixed with adamantyl (Ad)-terminated

  5. Multicolor Fluorescence Writing Based on Host-Guest Interactions and Force-Induced Fluorescence-Color Memory.

    Science.gov (United States)

    Matsunaga, Yuki; Yang, Jye-Shane

    2015-06-26

    A new strategy is reported for multicolor fluorescence writing on thin solid films with mechanical forces. This concept is illustrated by the use of a green-fluorescent pentiptycene derivative 1, which forms variably colored fluorescent exciplexes: a change from yellow to red was observed with anilines, and fluorescence quenching (a change to black) occurred in the presence of benzoquinone. Mechanical forces, such as grinding and shearing, induced a crystalline-to-amorphous phase transition in both the pristine and guest-adsorbed solids that led to a change in the fluorescence color (mechanofluorochromism) and a memory of the resulting color. Fluorescence drawings of five or more colors were created on glass or paper and could be readily erased by exposure to air and dichloromethane fumes. The structural and mechanistic aspects of the observations are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Insights into Unfolded Proteins from the Intrinsic phi/psi Propensities of the AAXAA Host-Guest Series

    Czech Academy of Sciences Publication Activity Database

    Towse, C. L.; Vymětal, Jiří; Vondrášek, Jiří; Daggett, V.

    2016-01-01

    Roč. 110, č. 2 (2016), s. 348-361 ISSN 0006-3495 R&D Projects: GA MŠk(CZ) LH11020 Institutional support: RVO:61388963 Keywords : polyproline-II helix * beta-sheet protein * random-coil behavior Subject RIV: BO - Biophysics Impact factor: 3.656, year: 2016

  7. Protein Data Bank (PDB): The Single Global Macromolecular Structure Archive.

    Science.gov (United States)

    Burley, Stephen K; Berman, Helen M; Kleywegt, Gerard J; Markley, John L; Nakamura, Haruki; Velankar, Sameer

    2017-01-01

    The Protein Data Bank (PDB)--the single global repository of experimentally determined 3D structures of biological macromolecules and their complexes--was established in 1971, becoming the first open-access digital resource in the biological sciences. The PDB archive currently houses ~130,000 entries (May 2017). It is managed by the Worldwide Protein Data Bank organization (wwPDB; wwpdb.org), which includes the RCSB Protein Data Bank (RCSB PDB; rcsb.org), the Protein Data Bank Japan (PDBj; pdbj.org), the Protein Data Bank in Europe (PDBe; pdbe.org), and BioMagResBank (BMRB; www.bmrb.wisc.edu). The four wwPDB partners operate a unified global software system that enforces community-agreed data standards and supports data Deposition, Biocuration, and Validation of ~11,000 new PDB entries annually (deposit.wwpdb.org). The RCSB PDB currently acts as the archive keeper, ensuring disaster recovery of PDB data and coordinating weekly updates. wwPDB partners disseminate the same archival data from multiple FTP sites, while operating complementary websites that provide their own views of PDB data with selected value-added information and links to related data resources. At present, the PDB archives experimental data, associated metadata, and 3D-atomic level structural models derived from three well-established methods: crystallography, nuclear magnetic resonance spectroscopy (NMR), and electron microscopy (3DEM). wwPDB partners are working closely with experts in related experimental areas (small-angle scattering, chemical cross-linking/mass spectrometry, Forster energy resonance transfer or FRET, etc.) to establish a federation of data resources that will support sustainable archiving and validation of 3D structural models and experimental data derived from integrative or hybrid methods.

  8. 50th Anniversary Perspective: Polymers with Complex Architectures

    KAUST Repository

    Polymeropoulos, George

    2017-02-09

    The scope of this Perspective is to highlight innovative contributions in the synthesis of well-defined complex macromolecular architectures and to emphasize the importance of these materials to polymer physical chemistry, physics, theory, and applications. In addition, this Perspective tries to enlighten the past and show possible pathways for the future. Among the plethora of polymerization methods, we briefly report the impact of the truly living and controlled/living polymerization techniques focusing mainly on anionic polymerization, the mother of all living and controlled/living polymerizations. Through anionic polymerization well-defined model polymers with complex macromolecular architectures having the highest molecular weight, structural and compositional homogeneity can be achieved. The synthesized structures include star, comb/graft, cyclic, branched and hyberbranched, dendritic, and multiblock multicomponent polymers. In our opinion, in addition to the work needed on the synthesis, properties, and application of copolymers with more than three chemically different blocks and complex architecture, the polymer chemists in the future should follow closer the approaches Nature, the perfect chemist, uses to make functional complex macromolecular structures by noncovalent chemistry. Moreover, development of new analytical methods for the characterization/purification of polymers with complex macromolecular architectures is essential for the synthesis and properties study of this family of polymeric materials.

  9. Cyclodextrin inclusion complex to improve physicochemical properties of herbicide bentazon: exploring better formulations.

    Directory of Open Access Journals (Sweden)

    Claudia Yáñez

    Full Text Available The knowledge of the host-guest complexes using cyclodextrins (CDs has prompted an increase in the development of new formulations. The capacity of these organic host structures of including guest within their hydrophobic cavities, improves physicochemical properties of the guest. In the case of pesticides, several inclusion complexes with cyclodextrins have been reported. However, in order to explore rationally new pesticide formulations, it is essential to know the effect of cyclodextrins on the properties of guest molecules. In this study, the inclusion complexes of bentazon (Btz with native βCD and two derivatives, 2-hydroxypropyl-β-cyclodextrin (HPCD and sulfobutylether-β-cyclodextrin (SBECD, were prepared by two methods: kneading and freeze-drying, and their characterization was investigated with different analytical techniques including Fourier transform infrared spectroscopy (FT-IR, differential thermal analysis (DTA, X-ray diffractometry (XRD and differential pulse voltammetry (DPV. All these approaches indicate that Btz forms inclusion complexes with CDs in solution and in solid state, with a stoichiometry of 1:1, although some of them are obtained in mixtures with free Btz. The calculated association constant of the Btz/HPCD complex by DPV was 244±19 M(-1 being an intermediate value compared with those obtained with βCD and SBECD. The use of CDs significantly increases Btz photostability, and depending on the CDs, decreases the surface tension. The results indicated that bentazon forms inclusion complexes with CDs showing improved physicochemical properties compared to free bentazon indicating that CDs may serve as excipient in herbicide formulations.

  10. Macromolecular competition titration method accessing thermodynamics of the unmodified macromolecule-ligand interactions through spectroscopic titrations of fluorescent analogs.

    Science.gov (United States)

    Bujalowski, Wlodzimierz; Jezewska, Maria J

    2011-01-01

    Analysis of thermodynamically rigorous binding isotherms provides fundamental information about the energetics of the ligand-macromolecule interactions and often an invaluable insight about the structure of the formed complexes. The Macromolecular Competition Titration (MCT) method enables one to quantitatively obtain interaction parameters of protein-nucleic acid interactions, which may not be available by other methods, particularly for the unmodified long polymer lattices and specific nucleic acid substrates, if the binding is not accompanied by adequate spectroscopic signal changes. The method can be applied using different fluorescent nucleic acids or fluorophores, although the etheno-derivatives of nucleic acid are especially suitable as they are relatively easy to prepare, have significant blue fluorescence, their excitation band lies far from the protein absorption spectrum, and the modification eliminates the possibility of base pairing with other nucleic acids. The MCT method is not limited to the specific size of the reference nucleic acid. Particularly, a simple analysis of the competition titration experiments is described in which the fluorescent, short fragment of nucleic acid, spanning the exact site-size of the protein-nucleic acid complex, and binding with only a 1:1 stoichiometry to the protein, is used as a reference macromolecule. Although the MCT method is predominantly discussed as applied to studying protein-nucleic acid interactions, it can generally be applied to any ligand-macromolecule system by monitoring the association reaction using the spectroscopic signal originating from the reference macromolecule in the presence of the competing macromolecule, whose interaction parameters with the ligand are to be determined. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Macromolecular Competition Titration Method: Accessing Thermodynamics of the Unmodified Macromolecule–Ligand Interactions Through Spectroscopic Titrations of Fluorescent Analogs

    Science.gov (United States)

    Bujalowski, Wlodzimierz; Jezewska, Maria J.

    2011-01-01

    Analysis of thermodynamically rigorous binding isotherms provides fundamental information about the energetics of the ligand–macromolecule interactions and often an invaluable insight about the structure of the formed complexes. The Macromolecular Competition Titration (MCT) method enables one to quantitatively obtain interaction parameters of protein–nucleic acid interactions, which may not be available by other methods, particularly for the unmodified long polymer lattices and specific nucleic acid substrates, if the binding is not accompanied by adequate spectroscopic signal changes. The method can be applied using different fluorescent nucleic acids or fluorophores, although the etheno-derivatives of nucleic acid are especially suitable as they are relatively easy to prepare, have significant blue fluorescence, their excitation band lies far from the protein absorption spectrum, and the modification eliminates the possibility of base pairing with other nucleic acids. The MCT method is not limited to the specific size of the reference nucleic acid. Particularly, a simple analysis of the competition titration experiments is described in which the fluorescent, short fragment of nucleic acid, spanning the exact site-size of the protein–nucleic acid complex, and binding with only a 1:1 stoichiometry to the protein, is used as a reference macromolecule. Although the MCT method is predominantly discussed as applied to studying protein–nucleic acid interactions, it can generally be applied to any ligand–macromolecule system by monitoring the association reaction using the spectroscopic signal originating from the reference macromolecule in the presence of the competing macromolecule, whose interaction parameters with the ligand are to be determined. PMID:21195223

  12. An 'attachment kinetics-based' volume of fraction method for organic crystallization: a fluid-dynamic approach to macromolecular-crystal engineering

    International Nuclear Information System (INIS)

    Lappa, Marcello

    2003-01-01

    This analysis exhibits a strong interdisciplinary nature and deals with advances in protein (crystal) engineering models and computational methods as well as with novel results on the relative importance of 'controlling forces' in macromolecular crystal growth. The attention is focused in particular on microgravity fluid-dynamic aspects. From a numerical point of view, the growing crystal gives rise to a moving boundary problem. A 'kinetic-coefficient-based' volume tracking method is specifically and carefully developed according to the complex properties and mechanisms of macromolecular protein crystal growth taking into account the possibility of anisotropic (faceted) surface-orientation-dependent growth. The method is used to shed some light on the interplay of surface attachment kinetics and mass transport (diffusive or convective) in liquid phase and on several mechanisms still poorly understood. It is shown that the size of a growing crystal plays a 'critical role' in the relative importance of surface effects and in determining the intensity of convection. Convective effects, in turn, are found to impact growth rates, macroscopic structures of precipitates, particle size and morphology as well as the mechanisms driving growth. The paper introduces a novel computational method (that simulates the growth due to the slow addition of solute molecules to a lattice and can handle the shape of organic growing crystals under the influence of natural convection) and, at the same time, represents a quite exhaustive attempt to help organic crystal growers to discern the complex interrelations among the various parameters under one's control (that are not independent of one another) and to elaborate rational guidelines relating to physical factors that can influence the probability of success in crystallizing protein substances

  13. Thermal behaviour of zinc(II) 5-chlorosalicylate complex compounds

    Czech Academy of Sciences Publication Activity Database

    Györyová, K.; Chomič, J.; Kovářová, Jana

    2005-01-01

    Roč. 80, č. 2 (2005), s. 375-380 ISSN 1388-6150 Grant - others:Slovak Ministry of Education(SK) VEGA 1/2474/05 Institutional research plan: CEZ:AV0Z40500505 Keywords : caffeine * chlorosalicylate complexes * nicotinamide Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.425, year: 2005

  14. Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Coquel

    2013-04-01

    Full Text Available Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian. Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results provide evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3D individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on

  15. A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design.

    Directory of Open Access Journals (Sweden)

    Shane Ó Conchúir

    Full Text Available The development and validation of computational macromolecular modeling and design methods depend on suitable benchmark datasets and informative metrics for comparing protocols. In addition, if a method is intended to be adopted broadly in diverse biological applications, there needs to be information on appropriate parameters for each protocol, as well as metrics describing the expected accuracy compared to experimental data. In certain disciplines, there exist established benchmarks and public resources where experts in a particular methodology are encouraged to supply their most efficient implementation of each particular benchmark. We aim to provide such a resource for protocols in macromolecular modeling and design. We present a freely accessible web resource (https://kortemmelab.ucsf.edu/benchmarks to guide the development of protocols for protein modeling and design. The site provides benchmark datasets and metrics to compare the performance of a variety of modeling protocols using different computational sampling methods and energy functions, providing a "best practice" set of parameters for each method. Each benchmark has an associated downloadable benchmark capture archive containing the input files, analysis scripts, and tutorials for running the benchmark. The captures may be run with any suitable modeling method; we supply command lines for running the benchmarks using the Rosetta software suite. We have compiled initial benchmarks for the resource spanning three key areas: prediction of energetic effects of mutations, protein design, and protein structure prediction, each with associated state-of-the-art modeling protocols. With the help of the wider macromolecular modeling community, we hope to expand the variety of benchmarks included on the website and continue to evaluate new iterations of current methods as they become available.

  16. Grain sorghum dust increases macromolecular efflux from the in situ nasal mucosa.

    Science.gov (United States)

    Gao, X P

    1998-04-01

    The purpose of this study was to determine whether an aqueous extract of grain sorghum dust increases macromolecular efflux from the nasal mucosa in vivo and, if so, whether this response is mediated, in part, by substance P. Suffusion of grain sorghum dust extract on the in situ nasal mucosa of anesthetized hamsters elicits a significant increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass, 70 kDa; P grain sorghum dust elicits neurogenic plasma exudation from the in situ nasal mucosa.

  17. Evaluation of quantum-chemical methods of radiolysis stability for macromolecular structures

    International Nuclear Information System (INIS)

    Postolache, Cristian; Matei, Lidia

    2005-01-01

    The behavior of macromolecular structures in ionising fields was analyzed by quantum-chemical methods. In this study the primary radiolytic effect was analyzed using a two-step radiolytic mechanism: a) ionisation of molecule and spatial redistribution of atoms in order to reach a minimum value of energy, characteristic to the quantum state; b) neutralisation of the molecule by electron capture and its rapid dissociation into free radicals. Chemical bonds suspected to break are located in the distribution region of LUMO orbital and have minimal homolytic dissociation energies. Representative polymer structures (polyethylene, polypropylene, polystyrene, poly α and β polystyrene, polyisobutylene, polytetrafluoroethylene, poly methylsiloxanes) were analyzed. (authors)

  18. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    Science.gov (United States)

    Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L.; Armour, Wes; Waterman, David G.; Iwata, So; Evans, Gwyndaf

    2013-01-01

    The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein. PMID:23897484

  19. Remote Access to the PXRR Macromolecular Crystallography Facilities at the NSLS

    Energy Technology Data Exchange (ETDEWEB)

    A Soares; D Schneider; J Skinner; M Cowan; R Buono; H Robinson; A Heroux; M Carlucci-Dayton; A Saxena; R Sweet

    2011-12-31

    The most recent surge of innovations that have simplified and streamlined the process of determining macromolecular structures by crystallography owes much to the efforts of the structural genomics community. However, this was only the last step in a long evolution that saw the metamorphosis of crystallography from an heroic effort that involved years of dedication and skill into a straightforward measurement that is occasionally almost trivial. Many of the steps in this remarkable odyssey involved reducing the physical labor that is demanded of experimenters in the field. Other steps reduced the technical expertise required for conducting those experiments.

  20. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography.

    Science.gov (United States)

    Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L; Armour, Wes; Waterman, David G; Iwata, So; Evans, Gwyndaf

    2013-08-01

    The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein.

  1. Remote Access to the PXRR Macromolecular Crystallography Facilities at the NSLS

    International Nuclear Information System (INIS)

    Soares, A.; Schneider, D.; Skinner, J.; Cowan, M.; Buono, R.; Robinson, H.; Heroux, A.; Carlucci-Dayton, M.; Saxena, A.; Sweet, R.

    2008-01-01

    The most recent surge of innovations that have simplified and streamlined the process of determining macromolecular structures by crystallography owes much to the efforts of the structural genomics community. However, this was only the last step in a long evolution that saw the metamorphosis of crystallography from an heroic effort that involved years of dedication and skill into a straightforward measurement that is occasionally almost trivial. Many of the steps in this remarkable odyssey involved reducing the physical labor that is demanded of experimenters in the field. Other steps reduced the technical expertise required for conducting those experiments.

  2. Structure of valinomycin and its complexes

    Czech Academy of Sciences Publication Activity Database

    Hašek, Jindřich; Makrlík, E.; Dušek, Michal; Císařová, I.; Dohnálek, Jan; Dušková, Jarmila; Skálová, Tereza

    2009-01-01

    Roč. 16, 2a (2009), s. 30-31 ISSN 1211-5894. [Struktura - Colloquium of Czech and Slovak Crystallographic Association. Hluboká nad Vltavou, 22.06.2009-25.06.2009] R&D Projects: GA ČR GA305/07/1073; GA AV ČR IAA500500701 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z10100521 Keywords : valinomycin * complex * structure 8 hydration Subject RIV: CD - Macromolecular Chemistry

  3. A brief history of macromolecular crystallography, illustrated by a family tree and its Nobel fruits.

    Science.gov (United States)

    Jaskolski, Mariusz; Dauter, Zbigniew; Wlodawer, Alexander

    2014-09-01

    As a contribution to the celebration of the year 2014, declared by the United Nations to be 'The International Year of Crystallography', the FEBS Journal is dedicating this issue to papers showcasing the intimate union between macromolecular crystallography and structural biology, both in historical perspective and in current research. Instead of a formal editorial piece, by way of introduction, this review discusses the most important, often iconic, achievements of crystallographers that led to major advances in our understanding of the structure and function of biological macromolecules. We identified at least 42 scientists who received Nobel Prizes in Physics, Chemistry or Medicine for their contributions that included the use of X-rays or neutrons and crystallography, including 24 who made seminal discoveries in macromolecular sciences. Our spotlight is mostly, but not only, on the recipients of this most prestigious scientific honor, presented in approximately chronological order. As a summary of the review, we attempt to construct a genealogy tree of the principal lineages of protein crystallography, leading from the founding members to the present generation. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  4. Long-wavelength macromolecular crystallography - First successful native SAD experiment close to the sulfur edge

    Science.gov (United States)

    Aurelius, O.; Duman, R.; El Omari, K.; Mykhaylyk, V.; Wagner, A.

    2017-11-01

    Phasing of novel macromolecular crystal structures has been challenging since the start of structural biology. Making use of anomalous diffraction of natively present elements, such as sulfur and phosphorus, for phasing has been possible for some systems, but hindered by the necessity to access longer X-ray wavelengths in order to make most use of the anomalous scattering contributions of these elements. Presented here are the results from a first successful experimental phasing study of a macromolecular crystal structure at a wavelength close to the sulfur K edge. This has been made possible by the in-vacuum setup and the long-wavelength optimised experimental setup at the I23 beamline at Diamond Light Source. In these early commissioning experiments only standard data collection and processing procedures have been applied, in particular no dedicated absorption correction has been used. Nevertheless the success of the experiment demonstrates that the capability to extract phase information can be even further improved once data collection protocols and data processing have been optimised.

  5. Organ specific acute toxicity of the carcinogen trans-4-acetylaminostilbene is not correlated with macromolecular binding.

    Science.gov (United States)

    Pfeifer, A; Neumann, H G

    1986-09-01

    trans-4-Acetylaminostilbene (trans-AAS) is acutely toxic in rats and lesions are produced specifically in the glandular stomach. Toxicity is slightly increased by pretreating the animals with phenobarbital (PB) and is completely prevented by pretreatment with methylcholanthrene (MC). The prostaglandin inhibitors, indomethacin and acetyl salicylic acid, do not reduce toxicity. The high efficiency of MC suggested that toxicity is caused by reactive metabolites. trans-[3H]-AAS was administered orally to untreated and to PB- or MC-pretreated female Wistar rats and target doses in different tissues were measured by means of covalent binding to proteins, RNA and DNA. Macromolecular binding in the target tissue of poisoned animals was significantly lower than in liver and kidney and comparable to other non-target tissues. Pretreatment with MC lowered macromolecular binding in all extrahepatic tissues but not in liver. These findings are not in line with tissue specific metabolic activation. The only unique property of the target tissue, glandular stomach, that we observed was a particular affinity for the systemically available parent compound. In the early phase of poisoning, tissue concentrations were exceedingly high and the stomach function was impaired.

  6. Can visco-elastic phase separation, macromolecular crowding and colloidal physics explain nuclear organisation?

    Directory of Open Access Journals (Sweden)

    Iborra Francisco J

    2007-04-01

    Full Text Available Abstract Background The cell nucleus is highly compartmentalized with well-defined domains, it is not well understood how this nuclear order is maintained. Many scientists are fascinated by the different set of structures observed in the nucleus to attribute functions to them. In order to distinguish functional compartments from non-functional aggregates, I believe is important to investigate the biophysical nature of nuclear organisation. Results The various nuclear compartments can be divided broadly as chromatin or protein and/or RNA based, and they have very different dynamic properties. The chromatin compartment displays a slow, constrained diffusional motion. On the other hand, the protein/RNA compartment is very dynamic. Physical systems with dynamical asymmetry go to viscoelastic phase separation. This phase separation phenomenon leads to the formation of a long-lived interaction network of slow components (chromatin scattered within domains rich in fast components (protein/RNA. Moreover, the nucleus is packed with macromolecules in the order of 300 mg/ml. This high concentration of macromolecules produces volume exclusion effects that enhance attractive interactions between macromolecules, known as macromolecular crowding, which favours the formation of compartments. In this paper I hypothesise that nuclear compartmentalization can be explained by viscoelastic phase separation of the dynamically different nuclear components, in combination with macromolecular crowding and the properties of colloidal particles. Conclusion I demonstrate that nuclear structure can satisfy the predictions of this hypothesis. I discuss the functional implications of this phenomenon.

  7. Time-efficient, high-resolution, whole brain three-dimensional macromolecular proton fraction mapping.

    Science.gov (United States)

    Yarnykh, Vasily L

    2016-05-01

    Macromolecular proton fraction (MPF) mapping is a quantitative MRI method that reconstructs parametric maps of a relative amount of macromolecular protons causing the magnetization transfer (MT) effect and provides a biomarker of myelination in neural tissues. This study aimed to develop a high-resolution whole brain MPF mapping technique using a minimal number of source images for scan time reduction. The described technique was based on replacement of an actually acquired reference image without MT saturation by a synthetic one reconstructed from R1 and proton density maps, thus requiring only three source images. This approach enabled whole brain three-dimensional MPF mapping with isotropic 1.25 × 1.25 × 1.25 mm(3) voxel size and a scan time of 20 min. The synthetic reference method was validated against standard MPF mapping with acquired reference images based on data from eight healthy subjects. Mean MPF values in segmented white and gray matter appeared in close agreement with no significant bias and small within-subject coefficients of variation (maps demonstrated sharp white-gray matter contrast and clear visualization of anatomical details, including gray matter structures with high iron content. The proposed synthetic reference method improves resolution of MPF mapping and combines accurate MPF measurements with unique neuroanatomical contrast features. © 2015 Wiley Periodicals, Inc.

  8. ISPyB: an information management system for synchrotron macromolecular crystallography.

    Science.gov (United States)

    Delagenière, Solange; Brenchereau, Patrice; Launer, Ludovic; Ashton, Alun W; Leal, Ricardo; Veyrier, Stéphanie; Gabadinho, José; Gordon, Elspeth J; Jones, Samuel D; Levik, Karl Erik; McSweeney, Seán M; Monaco, Stéphanie; Nanao, Max; Spruce, Darren; Svensson, Olof; Walsh, Martin A; Leonard, Gordon A

    2011-11-15

    Individual research groups now analyze thousands of samples per year at synchrotron macromolecular crystallography (MX) resources. The efficient management of experimental data is thus essential if the best possible experiments are to be performed and the best possible data used in downstream processes in structure determination pipelines. Information System for Protein crystallography Beamlines (ISPyB), a Laboratory Information Management System (LIMS) with an underlying data model allowing for the integration of analyses down-stream of the data collection experiment was developed to facilitate such data management. ISPyB is now a multisite, generic LIMS for synchrotron-based MX experiments. Its initial functionality has been enhanced to include improved sample tracking and reporting of experimental protocols, the direct ranking of the diffraction characteristics of individual samples and the archiving of raw data and results from ancillary experiments and post-experiment data processing protocols. This latter feature paves the way for ISPyB to play a central role in future macromolecular structure solution pipelines and validates the application of the approach used in ISPyB to other experimental techniques, such as biological solution Small Angle X-ray Scattering and spectroscopy, which have similar sample tracking and data handling requirements.

  9. New Programs Utilizing Light Scattering and Flow Imaging Techniques for Macromolecular Crystal Growth and Fluid Dynamics Studies

    Science.gov (United States)

    2003-01-01

    Dr. Phil Segre, a physicist by training, is a recent addition to the Biotech group, SD46, having joined NASA in August of 2000. Over the past two years he has been developing a laboratory for the study of macromolecular and protein crystal growth. The main apparatus for this work is a Dynamic Light Scattering apparatus, DLS, which is capable of making highly precise measurements of size distributions of both protein solutions and protein crystals. With Drs. Chernov and Thomas (USRA), he has begun a collaboration studying the affects of protein impurities on protein crystal growth and subsequent crystal quality. One of the hypotheses behind the differences between Earth and space grown protein crystals is that the absorption of harmful impurities is reduced in space due to the absence of convective flows. Using DLS measurements we are examining crystal growth with varying amounts of impurities and testing whether there is a strong physical basis behind this hypothesis. With Dr. Joe Ng of UAH he has been collaborating on a project to examine the folding/unfolding dynamics of large RNA complexes. A detailed understanding of this process is necessary for the handling of RNA in biotech applications, and the DLS instrument gives details and results beyond that of other instruments. With Prof. Jim McClymer of the University of Maine (summer faculty visitor to NASA in 2001, 2002), we have been studying the crystallization process in model colloidal suspensions whose behavior in some cases can mimic that of much smaller protein solutions. An understanding of the self-assembly of colloids is the first step in the process of engineering novel materials for photonic and light switching applications. Finally, he has begun an investigation into the physics of particle sedimentation. In addition to the DLS instrument he also has an instrument (called PIV) that can measure flow fields of fluids. The applications are to the dynamics of protein crystal motions both on earth and in

  10. MX1: a bending-magnet crystallography beamline serving both chemical and macromolecular crystallography communities at the Australian Synchrotron

    International Nuclear Information System (INIS)

    Cowieson, Nathan Philip; Aragao, David; Clift, Mark; Ericsson, Daniel J.; Gee, Christine; Harrop, Stephen J.; Mudie, Nathan; Panjikar, Santosh; Price, Jason R.; Riboldi-Tunnicliffe, Alan; Williamson, Rachel; Caradoc-Davies, Tom

    2015-01-01

    The macromolecular crystallography beamline MX1 at the Australian Synchrotron is described. MX1 is a bending-magnet crystallography beamline at the 3 GeV Australian Synchrotron. The beamline delivers hard X-rays in the energy range from 8 to 18 keV to a focal spot at the sample position of 120 µm FWHM. The beamline endstation and ancillary equipment facilitate local and remote access for both chemical and biological macromolecular crystallography. Here, the design of the beamline and endstation are discussed. The beamline has enjoyed a full user program for the last seven years and scientific highlights from the user program are also presented

  11. The effect of macromolecular crowding on the electrostatic component of barnase-barstar binding: a computational, implicit solvent-based study.

    Directory of Open Access Journals (Sweden)

    Helena W Qi

    Full Text Available Macromolecular crowding within the cell can impact both protein folding and binding. Earlier models of cellular crowding focused on the excluded volume, entropic effect of crowding agents, which generally favors compact protein states. Recently, other effects of crowding have been explored, including enthalpically-related crowder-protein interactions and changes in solvation properties. In this work, we explore the effects of macromolecular crowding on the electrostatic desolvation and solvent-screened interaction components of protein-protein binding. Our simple model enables us to focus exclusively on the electrostatic effects of water depletion on protein binding due to crowding, providing us with the ability to systematically analyze and quantify these potentially intuitive effects. We use the barnase-barstar complex as a model system and randomly placed, uncharged spheres within implicit solvent to model crowding in an aqueous environment. On average, we find that the desolvation free energy penalties incurred by partners upon binding are lowered in a crowded environment and solvent-screened interactions are amplified. At a constant crowder density (fraction of total available volume occupied by crowders, this effect generally increases as the radius of model crowders decreases, but the strength and nature of this trend can depend on the water probe radius used to generate the molecular surface in the continuum model. In general, there is huge variation in desolvation penalties as a function of the random crowder positions. Results with explicit model crowders can be qualitatively similar to those using a lowered "effective" solvent dielectric to account for crowding, although the "best" effective dielectric constant will likely depend on multiple system properties. Taken together, this work systematically demonstrates, quantifies, and analyzes qualitative intuition-based insights into the effects of water depletion due to crowding on the

  12. A Simple Polarimetry Technique for Predicting the Absolute ...

    African Journals Online (AJOL)

    NICOLAAS

    2015-08-28

    Aug 28, 2015 ... The method involves simply measuring the optical rotation of the host-guest inclusion complex .... masses of the so-obtained complexes and analyzed these using ... In essence, if a given quantity of compound X rotates plane.

  13. Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012)

    Science.gov (United States)

    Foffi, G.; Pastore, A.; Piazza, F.; Temussi, P. A.

    2013-08-01

    More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). Figure 1. Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international conference

  14. Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).

    Science.gov (United States)

    Foffi, G; Pastore, A; Piazza, F; Temussi, P A

    2013-08-02

    More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). [Formula: see text] Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international

  15. Macromolecular Rate Theory (MMRT) Provides a Thermodynamics Rationale to Underpin the Convergent Temperature Response in Plant Leaf Respiration

    Science.gov (United States)

    Liang, L. L.; Arcus, V. L.; Heskel, M.; O'Sullivan, O. S.; Weerasinghe, L. K.; Creek, D.; Egerton, J. J. G.; Tjoelker, M. G.; Atkin, O. K.; Schipper, L. A.

    2017-12-01

    Temperature is a crucial factor in determining the rates of ecosystem processes such as leaf respiration (R) - the flux of plant respired carbon dioxide (CO2) from leaves to the atmosphere. Generally, respiration rate increases exponentially with temperature as modelled by the Arrhenius equation, but a recent study (Heskel et al., 2016) showed a universally convergent temperature response of R using an empirical exponential/polynomial model whereby the exponent in the Arrhenius model is replaced by a quadratic function of temperature. The exponential/polynomial model has been used elsewhere to describe shoot respiration and plant respiration. What are the principles that underlie these empirical observations? Here, we demonstrate that macromolecular rate theory (MMRT), based on transition state theory for chemical kinetics, is equivalent to the exponential/polynomial model. We re-analyse the data from Heskel et al. 2016 using MMRT to show this equivalence and thus, provide an explanation based on thermodynamics, for the convergent temperature response of R. Using statistical tools, we also show the equivalent explanatory power of MMRT when compared to the exponential/polynomial model and the superiority of both of these models over the Arrhenius function. Three meaningful parameters emerge from MMRT analysis: the temperature at which the rate of respiration is maximum (the so called optimum temperature, Topt), the temperature at which the respiration rate is most sensitive to changes in temperature (the inflection temperature, Tinf) and the overall curvature of the log(rate) versus temperature plot (the so called change in heat capacity for the system, ). The latter term originates from the change in heat capacity between an enzyme-substrate complex and an enzyme transition state complex in enzyme-catalysed metabolic reactions. From MMRT, we find the average Topt and Tinf of R are 67.0±1.2 °C and 41.4±0.7 °C across global sites. The average curvature (average

  16. Proceedings of a one-week course on exploiting anomalous scattering in macromolecular structure determination (EMBO'07)

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, M.S.; Shepard, W.; Dauter, Z.; Leslie, A.; Diederichs, K.; Evans, G.; Svensson, O.; Schneider, T.; Bricogne, G.; Dauter, Z.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Leslie, A.; Kabsch, W.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Read, R.; Panjikar, S.; Pannu, N.S.; Dauter, Z.; Weiss, M.S.; McSweeney, S

    2007-07-01

    This course, which was directed to young scientists, illustrated both theoretical and practical aspects of macromolecular crystal structure solution using synchrotron radiation. Some software dedicated to data collection, processing and analysis were presented. This document gathers only the slides of the presentations.

  17. Macromolecular crowding compacts unfolded apoflavodoxin and causes severe aggregation of the off-pathway intermediate during apoflavodoxin folding

    NARCIS (Netherlands)

    Engel, R.; Westphal, A.H.; Huberts, D.; Nabuurs, S.M.; Lindhoud, S.; Visser, A.J.W.G.; Mierlo, van C.P.M.

    2008-01-01

    To understand how proteins fold in vivo, it is important to investigate the effects of macromolecular crowding on protein folding. Here, the influence of crowding on in vitro apoflavodoxin folding, which involves a relatively stable off-pathway intermediate with molten globule characteristics, is

  18. Proceedings of a one-week course on exploiting anomalous scattering in macromolecular structure determination (EMBO'07)

    International Nuclear Information System (INIS)

    Weiss, M.S.; Shepard, W.; Dauter, Z.; Leslie, A.; Diederichs, K.; Evans, G.; Svensson, O.; Schneider, T.; Bricogne, G.; Dauter, Z.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Leslie, A.; Kabsch, W.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Read, R.; Panjikar, S.; Pannu, N.S.; Dauter, Z.; Weiss, M.S.; McSweeney, S.

    2007-01-01

    This course, which was directed to young scientists, illustrated both theoretical and practical aspects of macromolecular crystal structure solution using synchrotron radiation. Some software dedicated to data collection, processing and analysis were presented. This document gathers only the slides of the presentations

  19. Probing the Interplay of Size, Shape, and Solution Environment in Macromolecular Diffusion Using a Simple Refraction Experiment

    Science.gov (United States)

    Mankidy, Bijith D.; Coutinho, Cecil A.; Gupta, Vinay K.

    2010-01-01

    The diffusion coefficient of polymers is a critical parameter in biomedicine, catalysis, chemical separations, nanotechnology, and other industrial applications. Here, measurement of macromolecular diffusion in solutions is described using a visually instructive, undergraduate-level optical refraction experiment based on Weiner's method. To…

  20. Proceedings of a one-week course on exploiting anomalous scattering in macromolecular structure determination (EMBO'07)

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, M S; Shepard, W; Dauter, Z; Leslie, A; Diederichs, K; Evans, G; Svensson, O; Schneider, T; Bricogne, G; Dauter, Z; Flensburg, C; Terwilliger, T; Lamzin, V; Leslie, A; Kabsch, W; Flensburg, C; Terwilliger, T; Lamzin, V; Read, R; Panjikar, S; Pannu, N S; Dauter, Z; Weiss, M S; McSweeney, S

    2007-07-01

    This course, which was directed to young scientists, illustrated both theoretical and practical aspects of macromolecular crystal structure solution using synchrotron radiation. Some software dedicated to data collection, processing and analysis were presented. This document gathers only the slides of the presentations.

  1. A Test of Macromolecular Crystallization in Microgravity: Large, Well-Ordered Insulin Crystals

    Science.gov (United States)

    Borgstahl, Gloria E. O.; Vahedi-Faridi, Ardeschir; Lovelace, Jeff; Bellamy, Henry D.; Snell, Edward H.; Whitaker, Ann F. (Technical Monitor)

    2001-01-01

    Crystals of insulin grown in microgravity on space shuttle mission STS-95 were extremely well-ordered and unusually large (many > 2 mm). The physical characteristics of six microgravity and six earth-grown crystals were examined by X-ray analysis employing superfine f slicing and unfocused synchrotron radiation. This experimental setup allowed hundreds of reflections to be precisely examined for each crystal in a short period of time. The microgravity crystals were on average 34 times larger, had 7 times lower mosaicity, had 54 times higher reflection peak heights and diffracted to significantly higher resolution than their earth grown counterparts. A single mosaic domain model could account for reflections in microgravity crystals whereas reflections from earth crystals required a model with multiple mosaic domains. This statistically significant and unbiased characterization indicates that the microgravity environment was useful for the improvement of crystal growth and resultant diffraction quality in insulin crystals and may be similarly useful for macromolecular crystals in general.

  2. Acoustic methods for high-throughput protein crystal mounting at next-generation macromolecular crystallographic beamlines.

    Science.gov (United States)

    Roessler, Christian G; Kuczewski, Anthony; Stearns, Richard; Ellson, Richard; Olechno, Joseph; Orville, Allen M; Allaire, Marc; Soares, Alexei S; Héroux, Annie

    2013-09-01

    To take full advantage of advanced data collection techniques and high beam flux at next-generation macromolecular crystallography beamlines, rapid and reliable methods will be needed to mount and align many samples per second. One approach is to use an acoustic ejector to eject crystal-containing droplets onto a solid X-ray transparent surface, which can then be positioned and rotated for data collection. Proof-of-concept experiments were conducted at the National Synchrotron Light Source on thermolysin crystals acoustically ejected onto a polyimide `conveyor belt'. Small wedges of data were collected on each crystal, and a complete dataset was assembled from a well diffracting subset of these crystals. Future developments and implementation will focus on achieving ejection and translation of single droplets at a rate of over one hundred per second.

  3. Functionalization of Planet-Satellite Nanostructures Revealed by Nanoscopic Localization of Distinct Macromolecular Species

    KAUST Repository

    Rossner, Christian

    2016-09-26

    The development of a straightforward method is reported to form hybrid polymer/gold planet-satellite nanostructures (PlSNs) with functional polymer. Polyacrylate type polymer with benzyl chloride in its backbone as a macromolecular tracer is synthesized to study its localization within PlSNs by analyzing the elemental distribution of chlorine. The functionalized nanohybrid structures are analyzed by scanning transmission electron microscopy, electron energy loss spectroscopy, and spectrum imaging. The results show that the RAFT (reversible addition-fragmentation chain transfer) polymers\\' sulfur containing end groups are colocalized at the gold cores, both within nanohybrids of simple core-shell morphology and within higher order PlSNs, providing microscopic evidence for the affinity of the RAFT group toward gold surfaces. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA., Weinheim.

  4. Integration and global analysis of isothermal titration calorimetry data for studying macromolecular interactions.

    Science.gov (United States)

    Brautigam, Chad A; Zhao, Huaying; Vargas, Carolyn; Keller, Sandro; Schuck, Peter

    2016-05-01

    Isothermal titration calorimetry (ITC) is a powerful and widely used method to measure the energetics of macromolecular interactions by recording a thermogram of differential heating power during a titration. However, traditional ITC analysis is limited by stochastic thermogram noise and by the limited information content of a single titration experiment. Here we present a protocol for bias-free thermogram integration based on automated shape analysis of the injection peaks, followed by combination of isotherms from different calorimetric titration experiments into a global analysis, statistical analysis of binding parameters and graphical presentation of the results. This is performed using the integrated public-domain software packages NITPIC, SEDPHAT and GUSSI. The recently developed low-noise thermogram integration approach and global analysis allow for more precise parameter estimates and more reliable quantification of multisite and multicomponent cooperative and competitive interactions. Titration experiments typically take 1-2.5 h each, and global analysis usually takes 10-20 min.

  5. Mix and Inject: Reaction Initiation by Diffusion for Time-Resolved Macromolecular Crystallography

    Directory of Open Access Journals (Sweden)

    Marius Schmidt

    2013-01-01

    Full Text Available Time-resolved macromolecular crystallography unifies structure determination with chemical kinetics, since the structures of transient states and chemical and kinetic mechanisms can be determined simultaneously from the same data. To start a reaction in an enzyme, typically, an initially inactive substrate present in the crystal is activated. This has particular disadvantages that are circumvented when active substrate is directly provided by diffusion. However, then it is prohibitive to use macroscopic crystals because diffusion times become too long. With small micro- and nanocrystals diffusion times are adequately short for most enzymes and the reaction can be swiftly initiated. We demonstrate here that a time-resolved crystallographic experiment becomes feasible by mixing substrate with enzyme nanocrystals which are subsequently injected into the X-ray beam of a pulsed X-ray source.

  6. OCTOPUS: an innovative multimodal diffractometer for neutron macromolecular crystallography across the length scales

    International Nuclear Information System (INIS)

    Blakeley, M.P.; Andersen, K.; Kreuz, M.; Giroud, B.; McSweeney, S.; Mitchell, E.; Teixeira, S.C.M.; Forsyth, V.T.

    2011-01-01

    We propose to construct a novel protein diffractometer at position H112B. The new instrument will deliver major efficiency gains, as well as offering greatly extended flexibility through the option of several easily interchangeable modes of operation. This proposal builds on the demonstrable need to extend ILL's capacity for high resolution structural studies of protein systems, as well as a need to widen the scope of biological crystallography - in particular for monochromatic studies at both high and low resolution. The development will be carried out in close collaboration with structural biologists at the ESRF, and engineered in such a way that the user interface of the instrument (from sample to software) will be transparently identifiable to a large, dynamic, and driven community of European synchrotron X-ray macromolecular crystallographers. (authors)

  7. Control and data acquisition system for the macromolecular crystallography beamline of SSRF

    International Nuclear Information System (INIS)

    Wang Qisheng; Huang Sheng; Sun Bo; Tang Lin; He Jianhua

    2012-01-01

    The macromolecular crystallography beamline BL17U1 of Shanghai Synchrotron Radiation Facility (SSRF) is an important platform for structure biological science. High performance of the beamline would benefit the users greatly in their experiment and data acquisition. To take full advantage of the state-of-the-art mechanical and physical design of the beamline, we have made a series of efforts to develop a robust control and data acquisition system, with user-friendly GUI. These were done by adopting EPICS and Blu-Ice systems on the BL17U1 beamline, with considerations on easy accommodation of new beeline components. In this paper, we report the integration of EPICS and Blu-Ice systems. By using the EPICS gateway interface and several new DHS, Blu-Ice was successfully established for the BL17U1 beamline. As a result, the experiment control and data acquisition system is reliable and functional for users. (authors)

  8. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    DEFF Research Database (Denmark)

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.

    2017-01-01

    orders of magnitude. Data values also have greatly varying magnitudes. Standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME......Constraint-Based Reconstruction and Analysis (COBRA) is currently the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many...... models have 70,000 constraints and variables and will grow larger). We have developed a quadrupleprecision version of our linear and nonlinear optimizer MINOS, and a solution procedure (DQQ) involving Double and Quad MINOS that achieves reliability and efficiency for ME models and other challenging...

  9. Structure, function and folding of phosphoglycerate kinase are strongly perturbed by macromolecular crowding.

    Science.gov (United States)

    Samiotakis, Antonios; Dhar, Apratim; Ebbinghaus, Simon; Nienhaus, Lea; Homouz, Dirar; Gruebele, Martin; Cheung, Margaret

    2010-10-01

    We combine experiment and computer simulation to show how macromolecular crowding dramatically affects the structure, function and folding landscape of phosphoglycerate kinase (PGK). Fluorescence labeling shows that compact states of yeast PGK are populated as the amount of crowding agents (Ficoll 70) increases. Coarse-grained molecular simulations reveal three compact ensembles: C (crystal structure), CC (collapsed crystal) and Sph (spherical compact). With an adjustment for viscosity, crowded wild type PGK and fluorescent PGK are about 15 times or more active in 200 mg/ml Ficoll than in aqueous solution. Our results suggest a new solution to the classic problem of how the ADP and diphosphoglycerate binding sites of PGK come together to make ATP: rather than undergoing a hinge motion, the ADP and substrate sites are already located in proximity under crowded conditions that mimic the in vivo conditions under which the enzyme actually operates.

  10. Macromolecular contrast media. A new approach for characterising breast tumors with MR-mammography

    International Nuclear Information System (INIS)

    Daldrup, H.E.; Gossmann, A.; Koeln Univ.; Wendland, M.; Brasch, R.C.; Rosenau, W.

    1997-01-01

    The value of macromolecular contrast agents (MMCM) for the characterization of benign and malignant breast tumors will be demonstrated in this review. Animal studies suggest a high potential of MMCM to increase the specificity of MR-mammography. The concept of tumor differentiation is based on the pathological hyperpermeability of microvessels in malignant tumors. MMCM show a leak into the interstitium of carcinomas, whereas they are confined to the intravascular space in benign tumors. Capabilities and limitations of the MMCM-prototype. Albumin-Gd-DTPA, for breast tumor characterization will be summarized and compared to the standard low molecular weight contrast agent Gd-DTPA. Initial experience with new MMCM, such as Dendrimers, Gd-DTPA-Polylysine and MS-325 will be outlined. The potential of 'blood-pool'-iron oxides, such as AMI-227 for the evaluation of tumor microvascular permeabilities will be discussed. (orig.) [de

  11. DA+ data acquisition and analysis software at the Swiss Light Source macromolecular crystallography beamlines.

    Science.gov (United States)

    Wojdyla, Justyna Aleksandra; Kaminski, Jakub W; Panepucci, Ezequiel; Ebner, Simon; Wang, Xiaoqiang; Gabadinho, Jose; Wang, Meitian

    2018-01-01

    Data acquisition software is an essential component of modern macromolecular crystallography (MX) beamlines, enabling efficient use of beam time at synchrotron facilities. Developed at the Paul Scherrer Institute, the DA+ data acquisition software is implemented at all three Swiss Light Source (SLS) MX beamlines. DA+ consists of distributed services and components written in Python and Java, which communicate via messaging and streaming technologies. The major components of DA+ are the user interface, acquisition engine, online processing and database. Immediate data quality feedback is achieved with distributed automatic data analysis routines. The software architecture enables exploration of the full potential of the latest instrumentation at the SLS MX beamlines, such as the SmarGon goniometer and the EIGER X 16M detector, and development of new data collection methods.

  12. Optimization of selective inversion recovery magnetization transfer imaging for macromolecular content mapping in the human brain.

    Science.gov (United States)

    Dortch, Richard D; Bagnato, Francesca; Gochberg, Daniel F; Gore, John C; Smith, Seth A

    2018-03-24

    To optimize a selective inversion recovery (SIR) sequence for macromolecular content mapping in the human brain at 3.0T. SIR is a quantitative method for measuring magnetization transfer (qMT) that uses a low-power, on-resonance inversion pulse. This results in a biexponential recovery of free water signal that can be sampled at various inversion/predelay times (t I/ t D ) to estimate a subset of qMT parameters, including the macromolecular-to-free pool-size-ratio (PSR), the R 1 of free water (R 1f ), and the rate of MT exchange (k mf ). The adoption of SIR has been limited by long acquisition times (≈4 min/slice). Here, we use Cramér-Rao lower bound theory and data reduction strategies to select optimal t I /t D combinations to reduce imaging times. The schemes were experimentally validated in phantoms, and tested in healthy volunteers (N = 4) and a multiple sclerosis patient. Two optimal sampling schemes were determined: (i) a 5-point scheme (k mf estimated) and (ii) a 4-point scheme (k mf assumed). In phantoms, the 5/4-point schemes yielded parameter estimates with similar SNRs as our previous 16-point scheme, but with 4.1/6.1-fold shorter scan times. Pair-wise comparisons between schemes did not detect significant differences for any scheme/parameter. In humans, parameter values were consistent with published values, and similar levels of precision were obtained from all schemes. Furthermore, fixing k mf reduced the sensitivity of PSR to partial-volume averaging, yielding more consistent estimates throughout the brain. qMT parameters can be robustly estimated in ≤1 min/slice (without independent measures of ΔB 0 , B1+, and T 1 ) when optimized t I -t D combinations are selected. © 2018 International Society for Magnetic Resonance in Medicine.

  13. Macromolecular composition of terrestrial and marine organic matter in sediments across the East Siberian Arctic Shelf

    Science.gov (United States)

    Sparkes, Robert B.; Doğrul Selver, Ayça; Gustafsson, Örjan; Semiletov, Igor P.; Haghipour, Negar; Wacker, Lukas; Eglinton, Timothy I.; Talbot, Helen M.; van Dongen, Bart E.

    2016-10-01

    Mobilisation of terrestrial organic carbon (terrOC) from permafrost environments in eastern Siberia has the potential to deliver significant amounts of carbon to the Arctic Ocean, via both fluvial and coastal erosion. Eroded terrOC can be degraded during offshore transport or deposited across the wide East Siberian Arctic Shelf (ESAS). Most studies of terrOC on the ESAS have concentrated on solvent-extractable organic matter, but this represents only a small proportion of the total terrOC load. In this study we have used pyrolysis-gas chromatography-mass spectrometry (py-GCMS) to study all major groups of macromolecular components of the terrOC; this is the first time that this technique has been applied to the ESAS. This has shown that there is a strong offshore trend from terrestrial phenols, aromatics and cyclopentenones to marine pyridines. There is good agreement between proportion phenols measured using py-GCMS and independent quantification of lignin phenol concentrations (r2 = 0.67, p radiocarbon data for bulk OC (14COC) which, when coupled with previous measurements, allows us to produce the most comprehensive 14COC map of the ESAS to date. Combining the 14COC and py-GCMS data suggests that the aromatics group of compounds is likely sourced from old, aged terrOC, in contrast to the phenols group, which is likely sourced from modern woody material. We propose that an index of the relative proportions of phenols and pyridines can be used as a novel terrestrial vs. marine proxy measurement for macromolecular organic matter. Principal component analysis found that various terrestrial vs. marine proxies show different patterns across the ESAS, and it shows that multiple river-ocean transects of surface sediments transition from river-dominated to coastal-erosion-dominated to marine-dominated signatures.

  14. Development of an online UV–visible microspectrophotometer for a macromolecular crystallography beamline

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Nobutaka, E-mail: nobutaka.shimizu@kek.jp [SPring-8/JASRI, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Shimizu, Tetsuya [RIKEN SPring-8 Center, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Baba, Seiki; Hasegawa, Kazuya [SPring-8/JASRI, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); Yamamoto, Masaki [RIKEN SPring-8 Center, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Kumasaka, Takashi [SPring-8/JASRI, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan)

    2013-11-01

    An online UV–visible microspectrophotometer has been developed for the macromolecular crystallography beamline at SPring-8. Details of this spectrophotometer are reported. Measurement of the UV–visible absorption spectrum is a convenient technique for detecting chemical changes of proteins, and it is therefore useful to combine spectroscopy and diffraction studies. An online microspectrophotometer for the UV–visible region was developed and installed on the macromolecular crystallography beamline, BL38B1, at SPring-8. This spectrophotometer is equipped with a difference dispersive double monochromator, a mercury–xenon lamp as the light source, and a photomultiplier as the detector. The optical path is mostly constructed using mirrors, in order to obtain high brightness in the UV region, and the confocal optics are assembled using a cross-slit diaphragm like an iris to eliminate stray light. This system can measure optical densities up to a maximum of 4.0. To study the effect of radiation damage, preliminary measurements of glucose isomerase and thaumatin crystals were conducted in the UV region. Spectral changes dependent on X-ray dose were observed at around 280 nm, suggesting that structural changes involving Trp or Tyr residues occurred in the protein crystal. In the case of the thaumatin crystal, a broad peak around 400 nm was also generated after X-ray irradiation, suggesting the cleavage of a disulfide bond. Dose-dependent spectral changes were also observed in cryo-solutions alone, and these changes differed with the composition of the cryo-solution. These responses in the UV region are informative regarding the state of the sample; consequently, this device might be useful for X-ray crystallography.

  15. Superhydrophobic hybrid membranes by grafting arc-like macromolecular bridges on graphene sheets: Synthesis, characterization and properties

    Science.gov (United States)

    Mo, Zhao-Hua; Luo, Zheng; Huang, Qiang; Deng, Jian-Ping; Wu, Yi-Xian

    2018-05-01

    Grafting single end-tethered polymer chains on the surface of graphene is a conventional way to modify the surface properties of graphene oxide. However, grafting arc-like macromolecular bridges on graphene surfaces has been barely reported. Herein, a novel arc-like polydimethylsiloxane (PDMS) macromolecular bridges grafted graphene sheets (GO-g-Arc PDMS) was successfully synthesized via a confined interface reaction at 90 °C. Both the hydrophilic α- and ω-amino groups of linear hydrophobic NH2-PDMS-NH2 macromolecular chains rapidly reacted with epoxy and carboxyl groups on the surfaces of graphene oxide in water suspension to form arc-like PDMS macromolecular bridges on graphene sheets. The grafting density of arc-like PDMS bridges on graphene sheets can reach up to 0.80 mmol g-1 or 1.32 arc-like bridges per nm2 by this confined interface reaction. The water contact angle (WCA) of the hybrid membrane could be increased with increasing both the grafting density and content of covalent arc-like bridges architecture. The superhydrophobic hybrid membrane with a WCA of 153.4° was prepared by grinding of the above arc-like PDMS bridges grafted graphene hybrid, dispersing in ethanol and filtrating by organic filter membrane. This superhydrophobic hybrid membrane shows good self-cleaning and complete oil-water separation properties, which provides potential applications in anticontamination coating and oil-water separation. To the best of our knowledge, this is the first report on the synthesis of functional hybrid membranes by grafting arc-like PDMS macromolecular bridges on graphene sheets via a confined interface reaction.

  16. Functionalized active-nucleus complex sensor

    Science.gov (United States)

    Pines, Alexander; Wemmer, David E.; Spence, Megan; Rubin, Seth

    2003-11-25

    A functionalized active-nucleus complex sensor that selectively associates with one or more target species, and a method for assaying and screening for one or a plurality of target species utilizing one or a plurality of functionalized active-nucleus complexes with at least two of the functionalized active-nucleus complexes having an attraction affinity to different corresponding target species. The functionalized active-nucleus complex has an active-nucleus and a targeting carrier. The method involves functionalizing an active-nucleus, for each functionalized active-nucleus complex, by incorporating the active-nucleus into a macromolucular or molecular complex that is capable of binding one of the target species and then bringing the macromolecular or molecular complexes into contact with the target species and detecting the occurrence of or change in a nuclear magnetic resonance signal from each of the active-nuclei in each of the functionalized active-nucleus complexes.

  17. Still more complexity in mammalian basement membranes

    DEFF Research Database (Denmark)

    Erickson, A C; Couchman, J R

    2000-01-01

    laminins, entactin-1/nidogen-1, Type IV collagen, and proteoglycans. However, within the past few years this complexity has increased as new components are described. The entactin/nidogen (E/N) family has expanded with the recent description of a new isoform, E/N-2/osteonidogen. Agrin and Type XVIII...... to be regulated through multiple, mostly domain-specific mechanisms. Understanding the functions of individual BM components and their assembly into macromolecular complexes is a considerable challenge that may increase as further BM and cell surface ligands are discovered for these proteins....

  18. Beta-Cyclodextrin Duplexes That Are Connected through Two Disulfide Bonds: Potent Hosts for the Complexation of Organic Molecules

    Czech Academy of Sciences Publication Activity Database

    Grishina, Anastasia; Stanchev, Stancho; Kumprecht, Lukáš; Buděšínský, Miloš; Pojarová, Michaela; Dušek, Michal; Rumlová, Michaela; Křížová, Ivana; Rulíšek, Lubomír; Kraus, Tomáš

    2012-01-01

    Roč. 18, č. 39 (2012), s. 12292-12304 ISSN 0947-6539 Grant - others:AV ČR(CZ) M200550904 Institutional support: RVO:61388963 ; RVO:68378271 Keywords : cucurbiturils * cyclodextrins * duplexes * host-guest systems * sulfur Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.831, year: 2012

  19. Complexation induced aggregation and deaggregation of acridine orange with sulfobutylether-β-cyclodextrin.

    Science.gov (United States)

    Sayed, Mhejabeen; Jha, Shruti; Pal, Haridas

    2017-09-13

    The present study reports a contrasting interaction behaviour of a biologically important dye, acridine orange (AOH + ), with a highly water soluble anionic host, based on a β-cyclodextrin (βCD) scaffold, i.e. sulfobutylether-β-cyclodextrin (SBEβCD), in comparison to native βCD. AOH + shows striking modulation in its photophysical properties, representing sequential changes in the modes of interaction with increasing SBEβCD concentration. At lower SBEβCD concentrations, AOH + preferentially binds in dimeric forms at the negatively charged SBEβCD portals, leading to strong fluorescence quenching. At higher SBEβCD concentrations, the dimeric dyes convert to monomeric forms and subsequently undergo both inclusion and exo complex formation with 1 : 1 stoichiometry, resulting in a large fluorescence enhancement. The intriguing observation of sequential fluorescence switch off and switch on for an AOH + -SBEβCD system is clearly facilitated by the presence of butylether chains with SO 3 - end groups at the portals of SBEβCD, providing an additional ion-ion interaction and much enhanced hydrophobic interaction for cationic AOH + compared to the native βCD host. To the best of our knowledge, such fluorescence off/on switching through multistep host-guest binding has not been reported so far in the literature. The present study not only provides a detailed insight into the unique binding interactions of AOH + with the SBEβCD host, but the findings of this study are also expected to be useful in designing supramolecular based drug formulations, drug delivery systems, sensors, and so on.

  20. Synthesis and structural evaluation of five coordination complexes of benzenepentacarboxylic acid with aza-donor ligands

    Science.gov (United States)

    Shimpi, Manishkumar R.; Biswas, Sharmita Nandy; Sarkar, Sohini; Pedireddi, V. R.

    2016-06-01

    Synthesis and structural features of five new coordination assemblies, [Co(bpyH)(H2O)5](BPCH)·(bpyH2)0.5·(H2O) (1a), [{Cu(H2O)3}·{Cu0.5(bpy)0.5(H2O)0.5}2(μ-BPCH)] (1b), [{Cd0.5(BPCH)}2·{Cd0.5(bpy)(H2O)2}2]·6(H2O) (1c), [Cu(BPCH2)(bpyeaH)]·2(H2O) (1d) and [Cd2 (bpyea)0.5(oxalate)0.5(μ-BPC) (H2O)]·(bpyeaH2)·2(H2O) (1e), have been reported. All the assemblies were prepared by co-crystallization of benzenepentacarboxylic acid (BPCH5) either with 4,4‧-bipyridine (bpy) or 1,2-bis(4-pyridyl)ethane (bpyea) in the presence of a transition metal ion (either Co(II), Cu(II) or Cd(II)) as the case may be. All the five compounds were synthesized by hydrothermal method and structures were determined by single crystal X-ray diffraction. All the obtained compounds, 1a-1e, exhibit distinct 3-D polymeric architectures either in the form of stacked layers or host-guest networks in which water molecules play a pivotal role providing additional stabilization by coordinate bonds as well as hydrogen bonds. Other non-covalent interactions such as C-H … π and π … π stacking also participate in the formation of exotic 3-D structures of these complexes.

  1. AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery

    International Nuclear Information System (INIS)

    Tsai, Yingssu; McPhillips, Scott E.; González, Ana; McPhillips, Timothy M.; Zinn, Daniel; Cohen, Aina E.; Feese, Michael D.; Bushnell, David; Tiefenbrunn, Theresa; Stout, C. David; Ludaescher, Bertram; Hedman, Britt; Hodgson, Keith O.; Soltis, S. Michael

    2013-01-01

    New software has been developed for automating the experimental and data-processing stages of fragment-based drug discovery at a macromolecular crystallography beamline. A new workflow-automation framework orchestrates beamline-control and data-analysis software while organizing results from multiple samples. AutoDrug is software based upon the scientific workflow paradigm that integrates the Stanford Synchrotron Radiation Lightsource macromolecular crystallography beamlines and third-party processing software to automate the crystallography steps of the fragment-based drug-discovery process. AutoDrug screens a cassette of fragment-soaked crystals, selects crystals for data collection based on screening results and user-specified criteria and determines optimal data-collection strategies. It then collects and processes diffraction data, performs molecular replacement using provided models and detects electron density that is likely to arise from bound fragments. All processes are fully automated, i.e. are performed without user interaction or supervision. Samples can be screened in groups corresponding to particular proteins, crystal forms and/or soaking conditions. A single AutoDrug run is only limited by the capacity of the sample-storage dewar at the beamline: currently 288 samples. AutoDrug was developed in conjunction with RestFlow, a new scientific workflow-automation framework. RestFlow simplifies the design of AutoDrug by managing the flow of data and the organization of results and by orchestrating the execution of computational pipeline steps. It also simplifies the execution and interaction of third-party programs and the beamline-control system. Modeling AutoDrug as a scientific workflow enables multiple variants that meet the requirements of different user groups to be developed and supported. A workflow tailored to mimic the crystallography stages comprising the drug-discovery pipeline of CoCrystal Discovery Inc. has been deployed and successfully

  2. Macromolecular composition of terrestrial and marine organic matter in sediments across the East Siberian Arctic Shelf

    Directory of Open Access Journals (Sweden)

    R. B. Sparkes

    2016-10-01

    Full Text Available Mobilisation of terrestrial organic carbon (terrOC from permafrost environments in eastern Siberia has the potential to deliver significant amounts of carbon to the Arctic Ocean, via both fluvial and coastal erosion. Eroded terrOC can be degraded during offshore transport or deposited across the wide East Siberian Arctic Shelf (ESAS. Most studies of terrOC on the ESAS have concentrated on solvent-extractable organic matter, but this represents only a small proportion of the total terrOC load. In this study we have used pyrolysis–gas chromatography–mass spectrometry (py-GCMS to study all major groups of macromolecular components of the terrOC; this is the first time that this technique has been applied to the ESAS. This has shown that there is a strong offshore trend from terrestrial phenols, aromatics and cyclopentenones to marine pyridines. There is good agreement between proportion phenols measured using py-GCMS and independent quantification of lignin phenol concentrations (r2 = 0.67, p < 0.01, n = 24. Furfurals, thought to represent carbohydrates, show no offshore trend and are likely found in both marine and terrestrial organic matter. We have also collected new radiocarbon data for bulk OC (14COC which, when coupled with previous measurements, allows us to produce the most comprehensive 14COC map of the ESAS to date. Combining the 14COC and py-GCMS data suggests that the aromatics group of compounds is likely sourced from old, aged terrOC, in contrast to the phenols group, which is likely sourced from modern woody material. We propose that an index of the relative proportions of phenols and pyridines can be used as a novel terrestrial vs. marine proxy measurement for macromolecular organic matter. Principal component analysis found that various terrestrial vs. marine proxies show different patterns across the ESAS, and it shows that multiple river–ocean transects of surface sediments transition from river-dominated to

  3. Large branched self-assembled DNA complexes

    International Nuclear Information System (INIS)

    Tosch, Paul; Waelti, Christoph; Middelberg, Anton P J; Davies, A Giles

    2007-01-01

    Many biological molecules have been demonstrated to self-assemble into complex structures and networks by using their very efficient and selective molecular recognition processes. The use of biological molecules as scaffolds for the construction of functional devices by self-assembling nanoscale complexes onto the scaffolds has recently attracted significant attention and many different applications in this field have emerged. In particular DNA, owing to its inherent sophisticated self-organization and molecular recognition properties, has served widely as a scaffold for various nanotechnological self-assembly applications, with metallic and semiconducting nanoparticles, proteins, macromolecular complexes, inter alia, being assembled onto designed DNA scaffolds. Such scaffolds may typically contain multiple branch-points and comprise a number of DNA molecules selfassembled into the desired configuration. Previously, several studies have used synthetic methods to produce the constituent DNA of the scaffolds, but this typically constrains the size of the complexes. For applications that require larger self-assembling DNA complexes, several tens of nanometers or more, other techniques need to be employed. In this article, we discuss a generic technique to generate large branched DNA macromolecular complexes

  4. Analysis of subcomponents of the gamma-aminobutyric acid/benzodiazepine receptor macromolecular complex in mammalian central nervous system

    International Nuclear Information System (INIS)

    McCabe, R.T.

    1987-01-01

    Since the presence of endogenous gamma-aminobutyric acid (GABA) may affect benzodiazepine binding to tissue sections in autoradiographic studies, a protocol designed to check for this influence has been investigated. [ 3 H]Flunitrazepam (1 nM) was used to label benzodiazepine receptors for autoradiographic localization. Bicuculline was added to the incubation medium of an additional set of tissue sections to antagonize any potential effect of endogenous GABA. Binding in these sections was compared to that occurring in another set in which excess GABA was added to create further GABA enhancement. Binding was also compared to adjacent sections which were treated similarly but also preincubated in distilled-deionized water to burst the cells by osmotic shock and eliminate endogenous GABA, thereby preventing any effect on benzodiazepine binding. The results indicated that endogenous GABA is indeed present in the slide-mounted tissue sections and is affecting benzodiazepine receptor binding differentially in various regions of the brain depending on the density of GABAergic innervation. Scatchard analysis of saturation data demonstrated that the alteration in BZ binding due to GABA was a result of a change in the affinity rather than number of receptors present

  5. Synthesis of branched polymers under continuous-flow microprocess: an improvement of the control of macromolecular architectures.

    Science.gov (United States)

    Bally, Florence; Serra, Christophe A; Brochon, Cyril; Hadziioannou, Georges

    2011-11-15

    Polymerization reactions can benefit from continuous-flow microprocess in terms of kinetics control, reactants mixing or simply efficiency when high-throughput screening experiments are carried out. In this work, we perform for the first time the synthesis of branched macromolecular architecture through a controlled/'living' polymerization technique, in tubular microreactor. Just by tuning process parameters, such as flow rates of the reactants, we manage to generate a library of polymers with various macromolecular characteristics. Compared to conventional batch process, polymerization kinetics shows a faster initiation step and more interestingly an improved branching efficiency. Due to reduced diffusion pathway, a characteristic of microsystems, it is thus possible to reach branched polymers exhibiting a denser architecture, and potentially a higher functionality for later applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Effects of far-ultraviolet radiation and oxygen on macromolecular synthesis and protein induction in Bacteroides fragilis BF-2

    International Nuclear Information System (INIS)

    Schumann, J.P.

    1983-11-01

    The study deals with the effects of far-UV radiation, oxygen and hydrogen peroxide on macromolecular synthesis and viability in the obligate anaerobe, Bacteroides fragilis, as well as the specific proteins induced in this organism by these different DNA damaging agents. Irradiation of Bacteroides fragilis cells with far-UV light (254 nm) under anaerobic conditions resulted in the immediate, rapid and extensive degradation of DNA which continued for 40 to 60 min after irradiation. DNA degradation after irradiation was inhibited by chloramphenicol and caffeine. RNA and protein synthesis were decreased by UV irradiation and the degree of inhibition was proportional to the UV dose. Colony formation was not affected immediately by UV irradiation and continued for a dose-dependent period prior to inhibition. The relationship between the DNA damage-induced proteins, macromolecular synthesis in damaged B. fragilis cells and the observed physiological responses and inducible repair phenomena after the different DNA damaging treatments in this anaerobe are discussed

  7. The 2D Structure of the T. brucei Preedited RPS12 mRNA Is Not Affected by Macromolecular Crowding

    Directory of Open Access Journals (Sweden)

    W.-Matthias Leeder

    2017-01-01

    Full Text Available Mitochondrial transcript maturation in African trypanosomes requires RNA editing to convert sequence-deficient pre-mRNAs into translatable mRNAs. The different pre-mRNAs have been shown to adopt highly stable 2D folds; however, it is not known whether these structures resemble the in vivo folds given the extreme “crowding” conditions within the mitochondrion. Here, we analyze the effects of macromolecular crowding on the structure of the mitochondrial RPS12 pre-mRNA. We use high molecular mass polyethylene glycol as a macromolecular cosolute and monitor the structure of the RNA globally and with nucleotide resolution. We demonstrate that crowding has no impact on the 2D fold and we conclude that the MFE structure in dilute solvent conditions represents a good proxy for the folding of the pre-mRNA in its mitochondrial solvent context.

  8. Distribution and enzymatic activity of heterotrophic bacteria decomposing selected macromolecular compounds in a Baltic Sea sandy beach

    Science.gov (United States)

    Podgórska, B.; Mudryk, Z. J.

    2003-03-01

    The potential capability to decompose macromolecular compounds, and the level of extracellular enzyme activities were determined in heterotrophic bacteria isolated from a sandy beach in Sopot on the Southern Baltic Sea coast. Individual isolates were capable of hydrolysing a wide spectrum of organic macromolecular compounds. Lipids, gelatine, and DNA were hydrolyzed most efficiently. Only a very small percentage of strains were able to decompose cellulose, and no pectinolytic bacteria were found. Except for starch-hydrolysis, no significant differences in the intensity of organic compound decomposition were recorded between horizontal and vertical profiles of the studied beach. Of all the studied extracellular enzymes, alkaline phosphatase, esterase lipase, and leucine acrylaminidase were most active; in contrast, the activity α-fucosidase, α-galactosidase and β-glucouronidase was the weakest. The level of extracellular enzyme activity was similar in both sand layers.

  9. Investigation of the effect of cucurbit[7]uril complexation on the photophysical and acid-base properties of the antimalarial drug quinine.

    Science.gov (United States)

    Mallick, Suman; Pal, Kaushik; Chandra, Falguni; Koner, Apurba L

    2016-11-09

    Host-guest complexation of mono and dicationic quinine with cucurbit[7]uril (CB7), a water-soluble macrocyclic host molecule, has been investigated. Job's plot, time-resolved anisotropy as well as concentration dependent NMR titration confirm the binding of two CB7 macrocycles with one quinine molecule. The binding affinity of dicationic quinine with CB7 is one order of magnitude higher than the binding constant of mono-cationic quinine. Such preferential binding results in one unit pK a shift in the ground-state of the quinoline ring. However, using fluorescence spectroscopy we have obtained two acid-dissociation constants, one for quinoline ring nitrogen and the other for the nitrogen of the quinuclidine moiety. In the excited state, CB7 complexation causes one unit pK a shift for the quinoline ring and 1.9 unit shift for the quinuclidine moiety. Interestingly, a large enhancement of fluorescence lifetime and anisotropy of quinine at pH 2.7 and pH 9.0 upon CB7 complexation was observed due to the restriction of conformational flexibility. Moreover, at pH 3.0, a large fluorescence enhancement of quinine due to CB7 complexation was observed and it was quite significant as compared to that of quinine in 0.1 (M) HCl without CB7. We believe that this study of quinine complexation with CB7 will reduce phototoxicity, increase bioavailability and offer an alternative standard for quantum yield measurements in an amiable condition.

  10. Release of polyanions from polyelectrolyte complexes by selective degradation of the polycation

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Boustta, M.; Leclercq, L.; Vert, M.

    2006-01-01

    Roč. 21, č. 2 (2006), s. 89-105 ISSN 0883-9115 Institutional research plan: CEZ:AV0Z40500505 Keywords : polyelectrolyte complex * enzymatic degradation * hydrolytic degradation Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.925, year: 2006

  11. Using Simple Manipulatives to Improve Student Comprehension of a Complex Biological Process: Protein Synthesis

    Science.gov (United States)

    Guzman, Karen; Bartlett, John

    2012-01-01

    Biological systems and living processes involve a complex interplay of biochemicals and macromolecular structures that can be challenging for undergraduate students to comprehend and, thus, misconceptions abound. Protein synthesis, or translation, is an example of a biological process for which students often hold many misconceptions. This article…

  12. Fourier-transform infrared spectroscopic study of a fractional-complexed polymer blend

    Czech Academy of Sciences Publication Activity Database

    Šturcová, Adriana; Kratochvíl, Jaroslav; Dybal, Jiří; Sikora, Antonín

    2014-01-01

    Roč. 59, October (2014), s. 200-207 ISSN 0014-3057 R&D Projects: GA ČR GAP108/12/0703 Institutional support: RVO:61389013 Keywords : miscible blend * inter-polymer complex * associative phase separation Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.005, year: 2014

  13. Study of physicochemical properties of zinc(II) butyrate complex compounds with some heterocyclic ligands

    Czech Academy of Sciences Publication Activity Database

    Szakácsová, M.; Györová, K.; Szunyogová, E.; Kovářová, Jana

    2002-01-01

    Roč. 96, - (2002), s. 383 ISSN 0009-2770. [Meeting of Chemical Societies /54./. 30.06.2002-04.07.2002, Brno] R&D Projects: GA AV ČR KSK4050111; GA MŠk VEGA 1/9247/02; GA MŠk VEGA 047/074 Keywords : butyrate complex compounds * heterocyclic ligands Subject RIV: CD - Macromolecular Chemistry

  14. Fractional complexation in a miscible polymer blend. Calorimetry and size exclusion chromatography

    Czech Academy of Sciences Publication Activity Database

    Kratochvíl, Jaroslav; Šturcová, Adriana; Sikora, Antonín; Dybal, Jiří

    2014-01-01

    Roč. 63, č. 8 (2014), s. 1406-1413 ISSN 0959-8103 R&D Projects: GA AV ČR IAA200500903; GA ČR GAP108/12/0703 Institutional support: RVO:61389013 Keywords : miscible blend * interpolymer complex * residual phase Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.409, year: 2014

  15. Interaction of cesium ions with calix[2]furan[4]pyrrole and its fluoride complex

    Czech Academy of Sciences Publication Activity Database

    Kříž, Jaroslav; Dybal, Jiří; Makrlík, E.; Kohnke, F. H.

    2012-01-01

    Roč. 541, 10 July (2012), s. 27-31 ISSN 0009-2614 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : calix[2]furan[4]pyrrole * Cs complex * NMR Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.145, year: 2012

  16. Experimental and DFT study on complexation of Eu3+ with a macrocyclic lactam receptor

    Czech Academy of Sciences Publication Activity Database

    Makrlík, E.; Záliš, Stanislav; Vaňura, P.; Sedláková, Zdeňka

    2013-01-01

    Roč. 24, č. 6 (2013), s. 2149-2153 ISSN 1040-0400 Institutional support: RVO:61388955 ; RVO:61389013 Keywords : europium * macrocyclic lactam receptor * complexation Subject RIV: CF - Physical ; Theoretical Chemistry; CD - Macromolecular Chemistry (UMCH-V) Impact factor: 1.900, year: 2013

  17. Complexation of Eu3+ with a macrocyclic lactam receptor: Experimental and theoretical study

    Czech Academy of Sciences Publication Activity Database

    Makrlík, E.; Záliš, Stanislav; Sedláková, Zdeňka; Vaňura, P.

    2013-01-01

    Roč. 1038, APR 2013 (2013), s. 216-219 ISSN 0022-2860 Institutional support: RVO:61388955 ; RVO:61389013 Keywords : europium * macrocyclic lactam receptor * complexation Subject RIV: CF - Physical ; Theoretical Chemistry; CD - Macromolecular Chemistry (UMCH-V) Impact factor: 1.599, year: 2013

  18. Macromolecular pHPMA-based nanoparticles with cholesterol for solid tumor targeting: behavior in HSA protein environment

    Czech Academy of Sciences Publication Activity Database

    Zhang, X.; Niebuur, B.-J.; Chytil, Petr; Etrych, Tomáš; Filippov, Sergey K.; Kikhney, A.; Wieland, D. C. F.; Svergun, D. I.; Papadakis, C. M.

    2018-01-01

    Roč. 19, č. 2 (2018), s. 470-480 ISSN 1525-7797 R&D Projects: GA ČR(CZ) GC15-10527J; GA MZd(CZ) NV16-28594A; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : polymer carriers * N-(2-hydroxypropyl)methacrylamide * tumor targeting Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 5.246, year: 2016

  19. Macromolecular basis for homocystein-induced changes in proteoglycan structure in growth and arteriosclerosis.

    Science.gov (United States)

    McCully, K S

    1972-01-01

    Cell culture monolayers deficient in cystathionine synthetase bound more inorganic sulfate than normal cell monolayers during growth to confluence; this was correlated with the production of granular proteoglycan by the abnormal cells and fibrillar proteoglycan by normal cells. Homocysteine was demonstrated to be an active precursor of esterified sulfate, confirming our previous finding of this sulfation pathway in liver. The cell cultures deficient in cystathionine synthetase were found to assume an abnormal cellular distribution on the surface of the culture dish, resembling the distribution assumed by neoplastic cells with loss of contact inhibition; the degree of abnormality of the cellular distribution was correlated with the amount of granular proteoglycan produced by the cells and the amount of inorganic sulfate binding by the cell monolayers. Pyridoxine was found to increase the growth rate of cell cultures from a patient with pyridoxineresponsive homocystinuria and to increase the production of fibrillar proteoglycan by the cells; no effect of pyridoxine was observed in the cell cultures from a patient who failed to respond to pyridoxine therapy. The findings suggest that the change in macromolecular conformation of cellular proteoglycans from fibrillar to granular is due to increased sulfation of the carbohydrate envelope of the molecule. The significance of the findings is related to the pathogenesis of homocystinuria, the phenomenon of contact inhibition, the action of growth hormone and initiation of arteriosclerotic plaques.

  20. Lactoferricin B inhibits bacterial macromolecular synthesis in Escherichia coli and Bacillus subtilis.

    Science.gov (United States)

    Ulvatne, Hilde; Samuelsen, Ørjan; Haukland, Hanne H; Krämer, Manuela; Vorland, Lars H

    2004-08-15

    Most antimicrobial peptides have an amphipathic, cationic structure, and an effect on the cytoplasmic membrane of susceptible bacteria has been postulated as the main mode of action. Other mechanisms have been reported, including inhibition of cellular functions by binding to DNA, RNA and proteins, and the inhibition of DNA and/or protein synthesis. Lactoferricin B (Lfcin B), a cationic peptide derived from bovine lactoferrin, exerts slow inhibitory and bactericidal activity and does not lyse susceptible bacteria, indicating a possible intracellular target. In the present study incorporation of radioactive precursors into DNA, RNA and proteins was used to demonstrate effects of Lfcin B on macromolecular synthesis in bacteria. In Escherichia coli UC 6782, Lfcin B induces an initial increase in protein and RNA synthesis and a decrease in DNA synthesis. After 10 min, the DNA-synthesis increases while protein and RNA-synthesis decreases significantly. In Bacillus subtilis, however, all synthesis of macromolecules is inhibited for at least 20 min. After 20 min RNA-synthesis increases. The results presented here show that Lfcin B at concentrations not sufficient to kill bacterial cells inhibits incorporation of radioactive precursors into macromolecules in both Gram-positive and Gram-negative bacteria.

  1. About Small Streams and Shiny Rocks: Macromolecular Crystal Growth in Microfluidics

    Science.gov (United States)

    vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    We are developing a novel technique with which we have grown diffraction quality protein crystals in very small volumes, utilizing chip-based, microfluidic ("LabChip") technology. With this technology volumes smaller than achievable with any laboratory pipette can be dispensed with high accuracy. We have performed a feasibility study in which we crystallized several proteins with the aid of a LabChip device. The protein crystals are of excellent quality as shown by X-ray diffraction. The advantages of this new technology include improved accuracy of dispensing for small volumes, complete mixing of solution constituents without bubble formation, highly repeatable recipe and growth condition replication, and easy automation of the method. We have designed a first LabChip device specifically for protein crystallization in batch mode and can reliably dispense and mix from a range of solution constituents. We are currently testing this design. Upon completion additional crystallization techniques, such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility aboard the International Space Station.

  2. Improved reproducibility of unit-cell parameters in macromolecular cryocrystallography by limiting dehydration during crystal mounting.

    Science.gov (United States)

    Farley, Christopher; Burks, Geoffry; Siegert, Thomas; Juers, Douglas H

    2014-08-01

    In macromolecular cryocrystallography unit-cell parameters can have low reproducibility, limiting the effectiveness of combining data sets from multiple crystals and inhibiting the development of defined repeatable cooling protocols. Here, potential sources of unit-cell variation are investigated and crystal dehydration during loop-mounting is found to be an important factor. The amount of water lost by the unit cell depends on the crystal size, the loop size, the ambient relative humidity and the transfer distance to the cooling medium. To limit water loss during crystal mounting, a threefold strategy has been implemented. Firstly, crystal manipulations are performed in a humid environment similar to the humidity of the crystal-growth or soaking solution. Secondly, the looped crystal is transferred to a vial containing a small amount of the crystal soaking solution. Upon loop transfer, the vial is sealed, which allows transport of the crystal at its equilibrated humidity. Thirdly, the crystal loop is directly mounted from the vial into the cold gas stream. This strategy minimizes the exposure of the crystal to relatively low humidity ambient air, improves the reproducibility of low-temperature unit-cell parameters and offers some new approaches to crystal handling and cryoprotection.

  3. A vibrating membrane bioreactor (VMBR): Macromolecular transmission-influence of extracellular polymeric substances

    DEFF Research Database (Denmark)

    Beier, Søren; Jonsson, Gunnar Eigil

    2009-01-01

    The vibrating membrane bioreactor (VMBR) system facilitates the possibility of conducting a separation of macromolecules (BSA) from larger biological components (yeast cells) with a relatively high and stable macromolecular transmission at sub-critical flux. This is not possible to achieve...... for a static non-vibrating membrane module. A BSA transmission of 74% has been measured in the separation of 4g/L BSA from 8 g/L dry weight yeast cells in suspension at sub-critical flux (20L/(m(2) h)). However, this transmission is lower than the 85% BSA transmission measured for at pure 4g/L BSA solution....... This can be ascribed to the presence of extracellular polymeric substances (EPS) from the yeast cells. The initial fouling rate for constant sub-critical flux filtration of unwashed yeast cells is 3-4 times larger than for washed yeast cells (18(mbar/h)/5(mbar/h)). At sub-critical flux, an EPS transmission...

  4. Using support vector machines to improve elemental ion identification in macromolecular crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Morshed, Nader [University of California, Berkeley, CA 94720 (United States); Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Echols, Nathaniel, E-mail: nechols@lbl.gov [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Adams, Paul D., E-mail: nechols@lbl.gov [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); University of California, Berkeley, CA 94720 (United States)

    2015-05-01

    A method to automatically identify possible elemental ions in X-ray crystal structures has been extended to use support vector machine (SVM) classifiers trained on selected structures in the PDB, with significantly improved sensitivity over manually encoded heuristics. In the process of macromolecular model building, crystallographers must examine electron density for isolated atoms and differentiate sites containing structured solvent molecules from those containing elemental ions. This task requires specific knowledge of metal-binding chemistry and scattering properties and is prone to error. A method has previously been described to identify ions based on manually chosen criteria for a number of elements. Here, the use of support vector machines (SVMs) to automatically classify isolated atoms as either solvent or one of various ions is described. Two data sets of protein crystal structures, one containing manually curated structures deposited with anomalous diffraction data and another with automatically filtered, high-resolution structures, were constructed. On the manually curated data set, an SVM classifier was able to distinguish calcium from manganese, zinc, iron and nickel, as well as all five of these ions from water molecules, with a high degree of accuracy. Additionally, SVMs trained on the automatically curated set of high-resolution structures were able to successfully classify most common elemental ions in an independent validation test set. This method is readily extensible to other elemental ions and can also be used in conjunction with previous methods based on a priori expectations of the chemical environment and X-ray scattering.

  5. A technique for determining the deuterium/hydrogen contrast map in neutron macromolecular crystallography.

    Science.gov (United States)

    Chatake, Toshiyuki; Fujiwara, Satoru

    2016-01-01

    A difference in the neutron scattering length between hydrogen and deuterium leads to a high density contrast in neutron Fourier maps. In this study, a technique for determining the deuterium/hydrogen (D/H) contrast map in neutron macromolecular crystallography is developed and evaluated using ribonuclease A. The contrast map between the D2O-solvent and H2O-solvent crystals is calculated in real space, rather than in reciprocal space as performed in previous neutron D/H contrast crystallography. The present technique can thus utilize all of the amplitudes of the neutron structure factors for both D2O-solvent and H2O-solvent crystals. The neutron D/H contrast maps clearly demonstrate the powerful detectability of H/D exchange in proteins. In fact, alternative protonation states and alternative conformations of hydroxyl groups are observed at medium resolution (1.8 Å). Moreover, water molecules can be categorized into three types according to their tendency towards rotational disorder. These results directly indicate improvement in the neutron crystal structure analysis. This technique is suitable for incorporation into the standard structure-determination process used in neutron protein crystallography; consequently, more precise and efficient determination of the D-atom positions is possible using a combination of this D/H contrast technique and standard neutron structure-determination protocols.

  6. In Vitro and In Vivo Biocompatibility Evaluation of Polyallylamine and Macromolecular Heparin Conjugates Modified Alginate Microbeads.

    Science.gov (United States)

    Vaithilingam, Vijayaganapathy; Steinkjer, Bjørg; Ryan, Liv; Larsson, Rolf; Tuch, Bernard Edward; Oberholzer, Jose; Rokstad, Anne Mari

    2017-09-15

    Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC). The PAV-CHC strategy resulted in uniform and stable coatings with increased anti-clot activity and low cytotoxicity. In human whole blood, PAV coating at high dose (100 µg/ml) induced elevated complement, leukocyte CD11b and inflammatory mediators, and in Wistar rats increased fibrotic overgrowth. Coating of high dose PAV with CHC significantly reduced these responses. Low dose PAV (10 µg/ml) ± CHC and unmodified alginate microbeads showed low responses. That the human whole blood inflammatory reactions paralleled the host response shows a link between inflammatory potential and initial fibrotic response. CHC possessed anti-inflammatory activity, but failed to improve overall biocompatibility. We conclude that the human whole blood assay is an efficient first-phase screening model for inflammation, and a guiding tool in development of new generation microspheres for cell encapsulation therapy.

  7. Photochemical internalisation of a macromolecular protein toxin using a cell penetrating peptide-photosensitiser conjugate.

    Science.gov (United States)

    Wang, Julie T-W; Giuntini, Francesca; Eggleston, Ian M; Bown, Stephen G; MacRobert, Alexander J

    2012-01-30

    Photochemical internalisation (PCI) is a site-specific technique for improving cellular delivery of macromolecular drugs. In this study, a cell penetrating peptide, containing the core HIV-1 Tat 48-57 sequence, conjugated with a porphyrin photosensitiser has been shown to be effective for PCI. Herein we report an investigation of the photophysical and photobiological properties of a water soluble bioconjugate of the cationic Tat peptide with a hydrophobic tetraphenylporphyrin derivative. The cellular uptake and localisation of the amphiphilic bioconjugate was examined in the HN5 human head and neck squamous cell carcinoma cell line. Efficient cellular uptake and localisation in endo/lysosomal vesicles was found using fluorescence detection, and light-induced, rupture of the vesicles resulting in a more diffuse intracellular fluorescence distribution was observed. Conjugation of the Tat sequence with a hydrophobic porphyrin thus enables cellular delivery of an amphiphilic photosensitiser which can then localise in endo/lysosomal membranes, as required for effective PCI treatment. PCI efficacy was tested in combination with a protein toxin, saporin, and a significant reduction in cell viability was measured versus saporin or photosensitiser treatment alone. This study demonstrates that the cell penetrating peptide-photosensitiser bioconjugation strategy is a promising and versatile approach for enhancing the therapeutic potential of bioactive agents through photochemical internalisation. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. The Effect of Attractive Interactions and Macromolecular Crowding on Crystallins Association.

    Directory of Open Access Journals (Sweden)

    Jiachen Wei

    Full Text Available In living systems proteins are typically found in crowded environments where their effective interactions strongly depend on the surrounding medium. Yet, their association and dissociation needs to be robustly controlled in order to enable biological function. Uncontrolled protein aggregation often causes disease. For instance, cataract is caused by the clustering of lens proteins, i.e., crystallins, resulting in enhanced light scattering and impaired vision or blindness. To investigate the molecular origins of cataract formation and to design efficient treatments, a better understanding of crystallin association in macromolecular crowded environment is needed. Here we present a theoretical study of simple coarse grained colloidal models to characterize the general features of how the association equilibrium of proteins depends on the magnitude of intermolecular attraction. By comparing the analytic results to the available experimental data on the osmotic pressure in crystallin solutions, we identify the effective parameters regimes applicable to crystallins. Moreover, the combination of two models allows us to predict that the number of binding sites on crystallin is small, i.e. one to three per protein, which is different from previous estimates. We further observe that the crowding factor is sensitive to the size asymmetry between the reactants and crowding agents, the shape of the protein clusters, and to small variations of intermolecular attraction. Our work may provide general guidelines on how to steer the protein interactions in order to control their association.

  9. Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

    Science.gov (United States)

    Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

    2017-12-01

    Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

  10. FitEM2EM--tools for low resolution study of macromolecular assembly and dynamics.

    Directory of Open Access Journals (Sweden)

    Ziv Frankenstein

    Full Text Available Studies of the structure and dynamics of macromolecular assemblies often involve comparison of low resolution models obtained using different techniques such as electron microscopy or atomic force microscopy. We present new computational tools for comparing (matching and docking of low resolution structures, based on shape complementarity. The matched or docked objects are represented by three dimensional grids where the value of each grid point depends on its position with regard to the interior, surface or exterior of the object. The grids are correlated using fast Fourier transformations producing either matches of related objects or docking models depending on the details of the grid representations. The procedures incorporate thickening and smoothing of the surfaces of the objects which effectively compensates for differences in the resolution of the matched/docked objects, circumventing the need for resolution modification. The presented matching tool FitEM2EMin successfully fitted electron microscopy structures obtained at different resolutions, different conformers of the same structure and partial structures, ranking correct matches at the top in every case. The differences between the grid representations of the matched objects can be used to study conformation differences or to characterize the size and shape of substructures. The presented low-to-low docking tool FitEM2EMout ranked the expected models at the top.

  11. Olfactory nerve transport of macromolecular drugs to the brain. A problem in olfactory impaired patients

    International Nuclear Information System (INIS)

    Shiga, Hideaki; Yamamoto, Junpei; Miwa, Takaki

    2012-01-01

    Nasal administration of macromolecular drugs (including peptides and nanoparticles) has the potential to enable drug delivery system beyond the blood brain barrier (BBB) via olfactory nerve transport. Basic research on drug deliver systems to the brain via nasal administration has been well reported. Insulin-like growth factor-I (IGF-I) is associated with the development and growth of the central nervous system. Clinical application of IGF-I with nasal administration is intended to enable drug delivery to brain through the BBB. Uptake of IGF-I in the olfactory bulb and central nervous system increased according to the dosage of nasally administered IGF-I in normal ICR mice, however IGF-I uptake in the trigeminal nerve remained unchanged. Olfactory nerve transport is important for the delivery of nasally administered IGF-I to the brain in vivo. Because a safe olfactory nerve tracer has not been clinically available, olfactory nerve transport has not been well studied in humans. Nasal thallium-201 ( 201 Tl) administration has been safely used to assess the direct pathway to the brain via the nose in healthy volunteers with a normal olfactory threshold. 201 Tl olfactory nerve transport has recently been shown to decrease in patients with hyposmia. The olfactory nerve transport function in patients with olfactory disorders will be determined using 201 Tl olfacto-scintigraphy for the exclusion of candidates in a clinical trial to assess the usefulness of nasal administration of IGF-I. (author)

  12. Macromolecular crowding-assisted fabrication of liquid-crystalline imprinted polymers.

    Science.gov (United States)

    Zhang, Chen; Zhang, Jing; Huang, Yan-Ping; Liu, Zhao-Sheng

    2015-04-01

    A macromolecular crowding-assisted liquid-crystalline molecularly imprinted monolith (LC-MIM) was prepared successfully for the first time. The imprinted stationary phase was synthesized with polymethyl methacrylate (PMMA) or polystyrene (PS) as the crowding agent, 4-cyanophenyl dicyclohexyl propylene (CPCE) as the liquid-crystal monomer, and hydroquinidine as the pseudo-template for the chiral separation of cinchona alkaloids in HPLC. A low level of cross-linker (26%) has been found to be sufficient to achieve molecular recognition on the crowding-assisted LC-MIM due to the physical cross-linking of mesogenic groups in place of chemical cross-linking, and baseline separation of quinidine and quinine could be achieved with good resolution (R(s) = 2.96), selectivity factor (α = 2.16), and column efficiency (N = 2650 plates/m). In contrast, the LC-MIM prepared without crowding agents displayed the smallest diastereoselectivity (α = 1.90), while the crowding-assisted MIM with high level of cross-linker (80%) obtained the greatest selectivity factor (α = 7.65), but the lowest column efficiency (N = 177 plates/m).

  13. Quickly Getting the Best Data from Your Macromolecular Crystals with a New Generation of Beamline Instruments

    International Nuclear Information System (INIS)

    Cipriani, Florent; Felisaz, Franck; Lavault, Bernard; Brockhauser, Sandor; Ravelli, Raimond; Launer, Ludovic; Leonard, Gordon; Renier, Michel

    2007-01-01

    While routine Macromolecular x-ray (MX) crystallography has relied on well established techniques for some years all the synchrotrons around the world are improving the throughput of their MX beamlines. Third generation synchrotrons provide small intense beams that make data collection of 5-10 microns sized crystals possible. The EMBL/ESRF MX Group in Grenoble has developed a new generation of instruments to easily collect data on 10 μm size crystals in an automated environment. This work is part of the Grenoble automation program that enables FedEx like crystallography using fully automated data collection and web monitored experiments. Seven ESRF beamlines and the MRC BM14 ESRF/CRG beamline are currently equipped with these latest instruments. We describe here the main features of the MD2x diffractometer family and the SC3 sample changer robot. Although the SC3 was primarily designed to increase the throughput of MX beamlines, it has also been shown to be efficient in improving the quality of the data collected. Strategies in screening a large number of crystals, selecting the best, and collecting a full data set from several re-oriented micro-crystals can now be run with minimum time and effort. The MD2x and SC3 instruments are now commercialised by the company ACCEL GmbH

  14. Macromolecular scaffolding: the relationship between nanoscale architecture and function in multichromophoric arrays for organic electronics.

    Science.gov (United States)

    Palermo, Vincenzo; Schwartz, Erik; Finlayson, Chris E; Liscio, Andrea; Otten, Matthijs B J; Trapani, Sara; Müllen, Klaus; Beljonne, David; Friend, Richard H; Nolte, Roeland J M; Rowan, Alan E; Samorì, Paolo

    2010-02-23

    The optimization of the electronic properties of molecular materials based on optically or electrically active organic building blocks requires a fine-tuning of their self-assembly properties at surfaces. Such a fine-tuning can be obtained on a scale up to 10 nm by mastering principles of supramolecular chemistry, i.e., by using suitably designed molecules interacting via pre-programmed noncovalent forces. The control and fine-tuning on a greater length scale is more difficult and challenging. This Research News highlights recent results we obtained on a new class of macromolecules that possess a very rigid backbone and side chains that point away from this backbone. Each side chain contains an organic semiconducting moiety, whose position and electronic interaction with neighboring moieties are dictated by the central macromolecular scaffold. A combined experimental and theoretical approach has made it possible to unravel the physical and chemical properties of this system across multiple length scales. The (opto)electronic properties of the new functional architectures have been explored by constructing prototypes of field-effect transistors and solar cells, thereby providing direct insight into the relationship between architecture and function.

  15. A decade of user operation on the macromolecular crystallography MAD beamline ID14-4 at the ESRF

    International Nuclear Information System (INIS)

    McCarthy, Andrew A.; Brockhauser, Sandor; Nurizzo, Didier; Theveneau, Pascal; Mairs, Trevor; Spruce, Darren; Guijarro, Matias; Lesourd, Marc; Ravelli, Raimond B. G.; McSweeney, Sean

    2009-01-01

    The improvement of the X-ray beam quality achieved on ID14-4 by the installation of new X-ray optical elements is described. ID14-4 at the ESRF is the first tunable undulator-based macromolecular crystallography beamline that can celebrate a decade of user service. During this time ID14-4 has not only been instrumental in the determination of the structures of biologically important molecules but has also contributed significantly to the development of various instruments, novel data collection schemes and pioneering radiation damage studies on biological samples. Here, the evolution of ID14-4 over the last decade is presented, and some of the major improvements that were carried out in order to maintain its status as one of the most productive macromolecular crystallography beamlines are highlighted. The experimental hutch has been upgraded to accommodate a high-precision diffractometer, a sample changer and a large CCD detector. More recently, the optical hutch has been refurbished in order to improve the X-ray beam quality on ID14-4 and to incorporate the most modern and robust optical elements used at other ESRF beamlines. These new optical elements will be described and their effect on beam stability discussed. These studies may be useful in the design, construction and maintenance of future X-ray beamlines for macromolecular crystallography and indeed other applications, such as those planned for the ESRF upgrade

  16. Predictive Mechanical Characterization of Macro-Molecular Material Chemistry Structures of Cement Paste at Nano Scale - Two-phase Macro-Molecular Structures of Calcium Silicate Hydrate, Tri-Calcium Silicate, Di-Calcium Silicate and Calcium Hydroxide

    Science.gov (United States)

    Padilla Espinosa, Ingrid Marcela

    Concrete is a hierarchical composite material with a random structure over a wide range of length scales. At submicron length scale the main component of concrete is cement paste, formed by the reaction of Portland cement clinkers and water. Cement paste acts as a binding matrix for the other components and is responsible for the strength of concrete. Cement paste microstructure contains voids, hydrated and unhydrated cement phases. The main crystalline phases of unhydrated cement are tri-calcium silicate (C3S) and di-calcium silicate (C2S), and of hydrated cement are calcium silicate hydrate (CSH) and calcium hydroxide (CH). Although efforts have been made to comprehend the chemical and physical nature of cement paste, studies at molecular level have primarily been focused on individual components. Present research focuses on the development of a method to model, at molecular level, and analysis of the two-phase combination of hydrated and unhydrated phases of cement paste as macromolecular systems. Computational molecular modeling could help in understanding the influence of the phase interactions on the material properties, and mechanical performance of cement paste. Present work also strives to create a framework for molecular level models suitable for potential better comparisons with low length scale experimental methods, in which the sizes of the samples involve the mixture of different hydrated and unhydrated crystalline phases of cement paste. Two approaches based on two-phase cement paste macromolecular structures, one involving admixed molecular phases, and the second involving cluster of two molecular phases are investigated. The mechanical properties of two-phase macromolecular systems of cement paste consisting of key hydrated phase CSH and unhydrated phases C3S or C2S, as well as CSH with the second hydrated phase CH were calculated. It was found that these cement paste two-phase macromolecular systems predicted an isotropic material behavior. Also

  17. Design, Synthesis and Characterization of Polyethylene-Based Macromolecular Architectures by Combining Polyhomologation with Powerful Linking Chemistry

    KAUST Repository

    Alkayal, Nazeeha

    2016-09-05

    Polyhomologation is a powerful method to prepare polyethylene-based materials with controlled molecular weight, topology and composition. This dissertation focuses on the discovery of new synthetic routes to prepare polyethylene-based macromolecular architectures by combining polyhomologation with highly orthogonal and efficient linking reactions such as Diels Alder, copper-catalyzed azide-alkyne cycloaddition (CuAAC), and Glaser. Taking advantage of functionalized polyhomologation initiators, as well as of the efficient coupling chemistry, we were able to synthesize various types of polymethylene (polyethylene)-based materials with complex architectures including linear co/terpolymers, graft terpolymers, and tadpole copolymers. In the first project, a facile synthetic route towards well-defined polymethylene-based co/terpolymers, by combining the anthracene/maleimide Diels–Alder reaction with polyhomologation, is presented. For the synthesis of diblock copolymers the following approach was applied: (a) synthesis of α-anthracene-ω-hydroxy-polymethylene by polyhomologation using tri (9 anthracene-methyl propyl ether) borane as the initiator, (b) synthesis of furan-protected-maleimide-terminated poly(ε-caprolactone) or polyethylene glycol and (c) Diels–Alder reaction between anthracene and maleimide-terminated polymers. In the case of triblock terpolymers, the α-anthracene-ω-hydroxy polymethylene was used as a macroinitiator for the ring-opening polymerization of D, L-lactide to afford an anthracene-terminated PM-b-PLA copolymer, followed by the Diels–Alder reaction with furan-protected maleimide-terminated poly (ε-caprolactone) or polyethylene glycol to give the triblock terpolymers. The synthetic methodology is general and potentially applicable to a range of polymers. The coupling reaction applied in the second project of this dissertation was copper-catalyzed “click” cycloaddition of azides and alkynes (CuAAC). Novel well-defined polyethylene

  18. Macromolecular crystallographic results obtained using a 2048x2048 CCD detector at CHESS

    International Nuclear Information System (INIS)

    Thiel, D.J.; Ealick, S.E.; Tate, M.W.; Gruner, S.M.; Eikenberry, E.F.

    1996-01-01

    We present results of macromolecular crystallographic experiments performed at the Cornell High Energy Synchrotron Source (CHESS) with a new CCD-based detector. This detector, installed in January 1995, complements a 1024x1024 CCD detector that has been in continuous operation at CHESS since December 1993. The new detector is based on a 4-port, 2048x2048 pixel CCD that is directly coupled to a Gd 2 O 2 S:Tb phosphor by a 3:1 tapered fiber optic. The active area of the phosphor is a square 82 mm on an edge. The readout time is 7 seconds. In the standard mode of operation, the pixel size at the active area is 41 μm on the edge leading to the capability of resolving approximately 200 orders of diffraction across the detector face. The detector also operates in a 1024x1024 mode in which the pixel size is electronically increased by a factor of 4 in area resulting in smaller data files and faster detector readout but at the expense of spatial resolution. Most of the data that has been collected by this detector has been collected in this mode. Dozens of data sets have been collected by many experimenters using this detector at CHESS during the four month period from its installation until the start of the six-month down period of the storage ring. The capabilities of the detector will be illustrated with results from various crystallographic measurements including experiments in which the recorded diffraction patterns extend in resolution as far as 1 A. The results demonstrate that this detector is capable of collecting data of quality at least equal to that of imaging plates but, in many circumstances, with much greater beamline efficiency. copyright 1996 American Institute of Physics

  19. Interpretation of ensembles created by multiple iterative rebuilding of macromolecular models

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V.; Adams, Paul D.; Moriarty, Nigel W.; Zwart, Peter; Read, Randy J.; Turk, Dusan; Hung, Li-Wei

    2007-01-01

    Heterogeneity in ensembles generated by independent model rebuilding principally reflects the limitations of the data and of the model-building process rather than the diversity of structures in the crystal. Automation of iterative model building, density modification and refinement in macromolecular crystallography has made it feasible to carry out this entire process multiple times. By using different random seeds in the process, a number of different models compatible with experimental data can be created. Sets of models were generated in this way using real data for ten protein structures from the Protein Data Bank and using synthetic data generated at various resolutions. Most of the heterogeneity among models produced in this way is in the side chains and loops on the protein surface. Possible interpretations of the variation among models created by repetitive rebuilding were investigated. Synthetic data were created in which a crystal structure was modelled as the average of a set of ‘perfect’ structures and the range of models obtained by rebuilding a single starting model was examined. The standard deviations of coordinates in models obtained by repetitive rebuilding at high resolution are small, while those obtained for the same synthetic crystal structure at low resolution are large, so that the diversity within a group of models cannot generally be a quantitative reflection of the actual structures in a crystal. Instead, the group of structures obtained by repetitive rebuilding reflects the precision of the models, and the standard deviation of coordinates of these structures is a lower bound estimate of the uncertainty in coordinates of the individual models

  20. a Study of the Concentration Dependence of Macromolecular Diffusion Using Photon Correlation Spectroscopy.

    Science.gov (United States)

    Marlowe, Robert Lloyd

    The dynamic light scattering technique of photon correlation spectroscopy has been used to investigate the dependence of the mutual diffusion coefficient of a macromolecular system upon concentration. The first part of the research was devoted to the design and construction of a single-clipping autocorrelator based on newly-developed integrated circuits. The resulting 128 channel instrument can perform real time autocorrelation for sample time intervals >(, )10 (mu)s, and batch processed autocorrelation for intervals down to 3 (mu)s. An improved design for a newer, all-digital autocorrelator is given. Homodyne light scattering experiments were then undertaken on monodisperse solutions of polystyrene spheres. The single-mode TEM(,oo) beam of an argon-ion laser ((lamda) = 5145 (ANGSTROM)) was used as the light source; all solutions were studied at room temperature. The scattering angle was varied from 30(DEGREES) to 110(DEGREES). Excellent agreement with the manufacturer's specification for the particle size was obtained from the photon correlation studies. Finally, aqueous solutions of the globular protein ovalbumin, ranging in concentration from 18.9 to 244.3 mg/ml, were illuminated under the same conditions of temperature and wavelength as before; the homodyne scattered light was detected at a fixed scattering angle of 30(DEGREES). The single-clipped photocount autocorrelation function was analyzed using the homodyne exponential integral method of Meneely et al. The resulting diffusion coefficients showed a general linear dependence upon concentration, as predicted by the generalized Stokes-Einstein equation. However, a clear peak in the data was evident at c (TURNEQ) 100 mg/ml, which could not be explained on the basis of a non -interacting particle theory. A semi-quantitative approach based on the Debye-Huckel theory of electrostatic interactions is suggested as the probable cause for the peak's rise, and an excluded volume effect for its decline.

  1. Novel use for polyvinylpyrrolidone as a macromolecular crowder for enhanced extracellular matrix deposition and cell proliferation.

    Science.gov (United States)

    Rashid, Rafi; Lim, Natalie Sheng Jie; Chee, Stella Min Ling; Png, Si Ning; Wohland, Thorsten; Raghunath, Michael

    2014-12-01

    Macromolecular crowding (MMC) is a biophysical effect that governs biochemical processes inside and outside of cells. Since standard cell culture media lack this effect, the physiological performance of differentiated and progenitor cells, including extracellular matrix (ECM) deposition, is impaired in vitro. To bring back physiological crowdedness to in vitro systems, we have previously introduced carbohydrate-based macromolecules to culture media and have achieved marked improvements with mixed MMC in terms of ECM deposition and differentiation of mesenchymal stem cells (MSCs). We show here that although this system is successful, it is limited, due to viscosity, to only 33% of the fractional volume occupancy (FVO) of full serum, which we calculated to have an FVO of approximately 54% v/v. We show here that full-serum FVO can be achieved using polyvinylpyrrolidone (PVP) 360 kDa. Under these conditions, ECM deposition in human fibroblasts and MSCs is on par, if not stronger than, with original MMC protocols using carbohydrates, but with a viscosity that is not significantly changed. In addition, we have found that the proliferation rate for bone marrow-derived MSCs and fibroblasts increases slightly in the presence of PVP360, similar to that observed with carbohydrate-based crowders. A palette of MMC compounds is now emerging that enables us to tune the crowdedness of culture media seamlessly from interstitial fluid (9% FVO), in which the majority of tissue cells might be based, to serum environments mimicking intravascular conditions. Despite identical FVO's, individual crowder size effects play a role and different cell types appear to have preferences in terms of FVO and the crowder that this is achieved with. However, in the quest of crowders that we have predicted to have a smoother regulatory approval path, PVP is a highly interesting compound, as it has been widely used in the medical and food industries and shows a novel promising use in cell culture and

  2. Improving 2D and 3D Skin In Vitro Models Using Macromolecular Crowding.

    Science.gov (United States)

    Benny, Paula; Badowski, Cedric; Lane, E Birgitte; Raghunath, Michael

    2016-08-22

    The glycoprotein family of collagens represents the main structural proteins in the human body, and are key components of biomaterials used in modern tissue engineering. A technical bottleneck is the deposition of collagen in vitro, as it is notoriously slow, resulting in sub-optimal formation of connective tissue and subsequent tissue cohesion, particularly in skin models. Here, we describe a method which involves the addition of differentially-sized sucrose co-polymers to skin cultures to generate macromolecular crowding (MMC), which results in a dramatic enhancement of collagen deposition. Particularly, dermal fibroblasts deposited a significant amount of collagen I/IV/VII and fibronectin under MMC in comparison to controls. The protocol also describes a method to decellularize crowded cell layers, exposing significant amounts of extracellular matrix (ECM) which were retained on the culture surface as evidenced by immunocytochemistry. Total matrix mass and distribution pattern was studied using interference reflection microscopy. Interestingly, fibroblasts, keratinocytes and co-cultures produced cell-derived matrices (CDM) of varying composition and morphology. CDM could be used as "bio-scaffolds" for secondary cell seeding, where the current use of coatings or scaffolds, typically from xenogenic animal sources, can be avoided, thus moving towards more clinically relevant applications. In addition, this protocol describes the application of MMC during the submerged phase of a 3D-organotypic skin co-culture model which was sufficient to enhance ECM deposition in the dermo-epidermal junction (DEJ), in particular, collagen VII, the major component of anchoring fibrils. Electron microscopy confirmed the presence of anchoring fibrils in cultures developed with MMC, as compared to controls. This is significant as anchoring fibrils tether the dermis to the epidermis, hence, having a pre-formed mature DEJ may benefit skin graft recipients in terms of graft stability and

  3. Development of an online UV-visible microspectrophotometer for a macromolecular crystallography beamline.

    Science.gov (United States)

    Shimizu, Nobutaka; Shimizu, Tetsuya; Baba, Seiki; Hasegawa, Kazuya; Yamamoto, Masaki; Kumasaka, Takashi

    2013-11-01

    Measurement of the UV-visible absorption spectrum is a convenient technique for detecting chemical changes of proteins, and it is therefore useful to combine spectroscopy and diffraction studies. An online microspectrophotometer for the UV-visible region was developed and installed on the macromolecular crystallography beamline, BL38B1, at SPring-8. This spectrophotometer is equipped with a difference dispersive double monochromator, a mercury-xenon lamp as the light source, and a photomultiplier as the detector. The optical path is mostly constructed using mirrors, in order to obtain high brightness in the UV region, and the confocal optics are assembled using a cross-slit diaphragm like an iris to eliminate stray light. This system can measure optical densities up to a maximum of 4.0. To study the effect of radiation damage, preliminary measurements of glucose isomerase and thaumatin crystals were conducted in the UV region. Spectral changes dependent on X-ray dose were observed at around 280 nm, suggesting that structural changes involving Trp or Tyr residues occurred in the protein crystal. In the case of the thaumatin crystal, a broad peak around 400 nm was also generated after X-ray irradiation, suggesting the cleavage of a disulfide bond. Dose-dependent spectral changes were also observed in cryo-solutions alone, and these changes differed with the composition of the cryo-solution. These responses in the UV region are informative regarding the state of the sample; consequently, this device might be useful for X-ray crystallography.

  4. Phase behaviour of macromolecular liquid crystalline materials. Computational studies at the molecular level

    International Nuclear Information System (INIS)

    Stimson, Lorna M.

    2003-01-01

    Molecular simulations provide an increasingly useful insight into the static and dynamic characteristics of materials. In this thesis molecular simulations of macro-molecular liquid crystalline materials are reported. The first liquid crystalline material that has been investigated is a side chain liquid crystal polymer (SCLCP). In this study semi-atomistic molecular dynamics simulations have been conducted at a range of temperatures and an aligning potential has been applied to mimic the effect of a magnetic field. In cooling the SCLCP from an isotropic melt, microphase separation was observed yielding a domain structure. The application of a magnetic field to this structure aligns the domains producing a stable smectic mesophase. This is the first study in which mesophases have been observed using an off-lattice model of a SCLCP. The second material that has been investigated is a dendrimer with terminal mesogenic functionalization. Here, a multi-scale approach has been taken with Monte Carlo studies of a single dendrimer molecule in the gas phase at the atomistic level, semi-atomistic molecular dynamics of a single molecule in liquid crystalline solvents and a coarse-grained molecular dynamics study of the dendrimer in the bulk. The coarse-grained model has been developed and parameterized using the results of the atomistic and semi-atomistic work. The single molecule studies showed that the liquid crystalline dendrimer was able to change its structure by conformational changes in the flexible chains that link the mesogenic groups to the core. Structural change was seen under the application of a mean field ordering potential in the gas phase, and in the presence of liquid crystalline solvents. No liquid crystalline phases were observed for the bulk phase studies of the coarse-grained model. However, when the length of the mesogenic units was increased there was some evidence for microphase separation in these systems. (author)

  5. Prospects for simulating macromolecular surfactant chemistry at the ocean–atmosphere boundary

    International Nuclear Information System (INIS)

    Elliott, S; Burrows, S M; Liu, X; Deal, C; Long, M; Ogunro, O; Wingenter, O; Russell, L M

    2014-01-01

    Biogenic lipids and polymers are surveyed for their ability to adsorb at the water–air interfaces associated with bubbles, marine microlayers and particles in the overlying boundary layer. Representative ocean biogeochemical regimes are defined in order to estimate local concentrations for the major macromolecular classes. Surfactant equilibria and maximum excess are then derived based on a network of model compounds. Relative local coverage and upward mass transport follow directly, and specific chemical structures can be placed into regional rank order. Lipids and denatured protein-like polymers dominate at the selected locations. The assigned monolayer phase states are variable, whether assessed along bubbles or at the atmospheric spray droplet perimeter. Since oceanic film compositions prove to be irregular, effects on gas and organic transfer are expected to exhibit geographic dependence as well. Moreover, the core arguments extend across the sea–air interface into aerosol–cloud systems. Fundamental nascent chemical properties including mass to carbon ratio and density depend strongly on the geochemical state of source waters. High surface pressures may suppress the Kelvin effect, and marine organic hygroscopicities are almost entirely unconstrained. While bubble adsorption provides a well-known means for transporting lipidic or proteinaceous material into sea spray, the same cannot be said of polysaccharides. Carbohydrates tend to be strongly hydrophilic so that their excess carbon mass is low despite stacked polymeric geometries. Since sugars are abundant in the marine aerosol, gel-based mechanisms may be required to achieve uplift. Uncertainties distill to a global scale dearth of information regarding two dimensional kinetics and equilibria. Nonetheless simulations are recommended, to initiate the process of systems level quantification. (papers)

  6. Design of cellulose ether-based macromolecular prodrugs of ciprofloxacin for extended release and enhanced bioavailability.

    Science.gov (United States)

    Amin, Muhammad; Abbas, Nazia Shahana; Hussain, Muhammad Ajaz; Sher, Muhammad; Edgar, Kevin J

    2018-07-01

    The present study reveals the syntheses of hydroxypropylcellulose‑(HPC) and hydroxyethylcellulose‑(HEC) based macromolecular prodrugs (MPDs) of ciprofloxacin (CIP) using homogeneous reaction methodology. Covalently loaded drug content (DC) of each prodrug was quantified using UV-Vis spectrophotometry to determine degree of substitution (DS). HPC-ciprofloxacin (HPC-CIP) conjugates showed DS of CIP in the range 0.87-1.15 whereas HEC-ciprofloxacin (HEC-CIP) conjugates showed DS range 0.51-0.75. Transmission electron microscopy revealed that HPC-CIP conjugate 2 and HEC-CIP conjugate 6 self-assembled into nanoparticles of 150-300 and 180-250nm, respectively. Size exclusion chromatography revealed HPC-CIP conjugate 2 and HEC-CIP conjugate 6 as monodisperse systems. In vitro drug release studies indicated 15 and 43% CIP release from HPC-CIP conjugate 2 after 6h in simulated gastric and simulated intestinal fluids (SGF and SIF), respectively. HEC-CIP conjugate 6 showed 16% and 46% release after 6h in SGF and SIF, respectively. HPC-CIP conjugate 2 and HEC-CIP conjugate 6 exhibited half-lives of 10.87 and 11.71h, respectively with area under the curve values of 164 and 175hμgmL -1 , respectively, indicating enhanced bioavailability and improved pharmacokinetic profiles in animal model. Equal antibacterial activities to that of unmodified CIP confirmed their competitive efficacies. Cytotoxicity studies supported their non-toxic nature and biocompatibility. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Phase-Separated Liposomes Enhance the Efficiency of Macromolecular Delivery to the Cellular Cytoplasm.

    Science.gov (United States)

    Imam, Zachary I; Kenyon, Laura E; Ashby, Grant; Nagib, Fatema; Mendicino, Morgan; Zhao, Chi; Gadok, Avinash K; Stachowiak, Jeanne C

    2017-10-01

    From viruses to organelles, fusion of biological membranes is used by diverse biological systems to deliver macromolecules across membrane barriers. Membrane fusion is also a potentially efficient mechanism for the delivery of macromolecular therapeutics to the cellular cytoplasm. However, a key shortcoming of existing fusogenic liposomal systems is that they are inefficient, requiring a high concentration of fusion-promoting lipids in order to cross cellular membrane barriers. Toward addressing this limitation, our experiments explore the extent to which membrane fusion can be amplified by using the process of lipid membrane phase separation to concentrate fusion-promoting lipids within distinct regions of the membrane surface. We used confocal fluorescence microscopy to investigate the integration of fusion-promoting lipids into a ternary lipid membrane system that separated into liquid-ordered and liquid-disordered membrane phases. Additionally, we quantified the impact of membrane phase separation on the efficiency with which liposomes transferred lipids and encapsulated macromolecules to cells, using a combination of confocal fluorescence imaging and flow cytometry. Here we report that concentrating fusion-promoting lipids within phase-separated lipid domains on the surfaces of liposomes significantly increases the efficiency of liposome fusion with model membranes and cells. In particular, membrane phase separation enhanced the delivery of lipids and model macromolecules to the cytoplasm of tumor cells by at least 4-fold in comparison to homogenous liposomes. Our findings demonstrate that phase separation can enhance membrane fusion by locally concentrating fusion-promoting lipids on the surface of liposomes. This work represents the first application of lipid membrane phase separation in the design of biomaterials-based delivery systems. Additionally, these results lay the ground work for developing fusogenic liposomes that are triggered by physical and

  8. Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent.

    Science.gov (United States)

    Jenjob, Ratchapol; Kun, Na; Ghee, Jung Yeon; Shen, Zheyu; Wu, Xiaoxia; Cho, Steve K; Lee, Don Haeng; Yang, Su-Geun

    2016-04-01

    In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd(3+), chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd(3+) in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd(3+) incubated with Ca(2+) was performed by using a dialysis membrane (MWCO 100-500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd(3+), the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd(3+) were released from Gd-DTPA-Pullulan after 2h incubation with Ca(2+) and Fe(2+), respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t1/2,α=0.43 h, t1/2,β=2.32 h), much longer than 0.11h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Experimental and Theoretical Investigations on the Supermolecular Structure of Isoliquiritigenin and 6-O-α-D-Maltosyl-β-cyclodextrin Inclusion Complex

    Directory of Open Access Journals (Sweden)

    Bin Li

    2015-08-01

    Full Text Available Isoliquiritigenin (ILTG possesses many pharmacological properties. However, its poor solubility and stability in water hinders its wide applications. The solubility of bioactive compounds can often be enhanced through preparation and delivery of various cyclodextrin (CD inclusion complexes. The 6-O-α-D-maltosyl-β-CD (G2-β-CD, as one of the newest developments of CDs, has high aqueous solubility and low toxicity, especially stable inclusion characteristics with bioactive compounds. In this work, we for the first time construct and characterize the supermolecular structure of ILTG/G2-β-CD by scanning electron microscopy (SEM, ultraviolet-visible spectroscopy (UV, Fourier transform infrared spectroscopy (FT-IR, and X-ray diffractometry (XRD. The solubility of ILTG in water at 25 °C rises from 0.003 to 0.717 mg/mL by the encapsulation with G2-β-CD. Our experimental observations on the presence of the ILTG/G2-β-CD inclusion complex are further supported by the ONIOM(our Own N-layer Integrated Orbital molecular Mechanics-based QM/MM (Quantum Mechanics/Molecular Mechanics calculations, typically substantiating these supermolecular characteristics, such as detailed structural assignments, preferred binding orientations, selectivity, solvent effects, interaction energies and forces of the ILTG/G2-β-CD inclusion complex. Our results have elucidated how ILTG interacts with G2-β-CD, demonstrating the primary host-guest interactions between ILTG and G2-β-CD, characterized by hydrogen bonds, hydrophobic interactions, electrostatic forces, and conformational effects, are favored for the formation of the ILTG/G2-β-CD inclusion.

  10. Permeability to macromolecular contrast media quantified by dynamic MRI correlates with tumor tissue assays of vascular endothelial growth factor (VEGF)

    International Nuclear Information System (INIS)

    Cyran, Clemens C.; Sennino, Barbara; Fu, Yanjun; Rogut, Victor; Shames, David M.; Chaopathomkul, Bundit; Wendland, Michael F.; McDonald, Donald M.; Brasch, Robert C.; Raatschen, Hans-Juergen

    2012-01-01

    Purpose: To correlate dynamic MRI assays of macromolecular endothelial permeability with microscopic area–density measurements of vascular endothelial growth factor (VEGF) in tumors. Methods and material: This study compared tumor xenografts from two different human cancer cell lines, MDA-MB-231 tumors (n = 5), and MDA-MB-435 (n = 8), reported to express respectively higher and lower levels of VEGF. Dynamic MRI was enhanced by a prototype macromolecular contrast medium (MMCM), albumin-(Gd-DTPA)35. Quantitative estimates of tumor microvascular permeability (K PS ; μl/min × 100 cm 3 ), obtained using a two-compartment kinetic model, were correlated with immunohistochemical measurements of VEGF in each tumor. Results: Mean K PS was 2.4 times greater in MDA-MB-231 tumors (K PS = 58 ± 30.9 μl/min × 100 cm 3 ) than in MDA-MB-435 tumors (K PS = 24 ± 8.4 μl/min × 100 cm 3 ) (p < 0.05). Correspondingly, the area–density of VEGF in MDA-MB-231 tumors was 2.6 times greater (27.3 ± 2.2%, p < 0.05) than in MDA-MB-435 cancers (10.5 ± 0.5%, p < 0.05). Considering all tumors without regard to cell type, a significant positive correlation (r = 0.67, p < 0.05) was observed between MRI-estimated endothelial permeability and VEGF immunoreactivity. Conclusion: Correlation of MRI assays of endothelial permeability to a MMCM and VEGF immunoreactivity of tumors support the hypothesis that VEGF is a major contributor to increased macromolecular permeability in cancers. When applied clinically, the MMCM-enhanced MRI approach could help to optimize the appropriate application of VEGF-inhibiting therapy on an individual patient basis.

  11. Nitrogen limitation in natural populations of cyanobacteria (Spirulina and Oscillatoria spp.) and its effect on macromolecular synthesis

    International Nuclear Information System (INIS)

    van Rijn, J.; Shilo, M.

    1986-01-01

    Natural populations of the cyanobacteria Spirulina species and Oscillatoria species obtained from Israeli fish ponds were limited in growth by nitrogen availability in summer. Physiological indicators for nitrogen limitation, such as phycocyanin, chlorophyll a, and carbohydrate content, did not show clear evidence for nitrogen limited growth, since these organisms are capable of vertical migration from and to the nitrogen-rich bottom. By means of 14 C labeling of the cells under simulated pond conditions followed by cell fractionation into macromolecular compounds, it was found that carbohydrates synthesized at the lighted surface were partially utilized for dark protein synthesis at the bottom of these ponds

  12. Comparison of two self-assembled macromolecular prodrug micelles with different conjugate positions of SN38 for enhancing antitumor activity

    Directory of Open Access Journals (Sweden)

    Liu Y

    2015-03-01

    Full Text Available Yi Liu,1 Hongyu Piao,1 Ying Gao,1 Caihong Xu,2 Ye Tian,1 Lihong Wang,1 Jinwen Liu,1 Bo Tang,1 Meijuan Zou,1 Gang Cheng1 1Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Food Science, Shenyang Normal University, Shenyang, Liaoning Province, People’s Republic of China Abstract: 7-Ethyl-10-hydroxycamptothecin (SN38, an active metabolite of irinotecan (CPT-11, is a remarkably potent antitumor agent. The clinical application of SN38 has been extremely restricted by its insolubility in water. In this study, we successfully synthesized two macromolecular prodrugs of SN38 with different conjugate positions (chitosan-(C10-OHSN38 and chitosan-(C20-OHSN38 to improve the water solubility and antitumor activity of SN38. These prodrugs can self-assemble into micelles in aqueous medium. The particle size, morphology, zeta potential, and in vitro drug release of SN38 and its derivatives, as well as their cytotoxicity, pharmacokinetics, and in vivo antitumor activity in a xenograft BALB/c mouse model were studied. In vitro, chitosan-(C10-OHSN38 (CS-(10sSN38 and chitosan-(C20-OHSN38 (CS-(20sSN38 were 13.3- and 25.9-fold more potent than CPT-11 in the murine colon adenocarcinoma cell line CT26, respectively. The area under the curve (AUC0–24 of SN38 after intravenously administering CS-(10sSN38 and CS-(20sSN38 to Sprague Dawley rats was greatly improved when compared with CPT-11 (both P<0.01. A larger AUC0–24 of CS-(20sSN38 was observed when compared to CS-(10sSN38 (P<0.05. Both of the novel self-assembled chitosan-SN38 prodrugs demonstrated superior anticancer activity to CPT-11 in the CT26 xenograft BALB/c mouse model. We have also investigated the differences between these macromolecular prodrug micelles with regards to enhancing the antitumor activity of SN38. CS-(20sSN38 exhibited better in vivo antitumor activity than CS-(10sSN38 at a dose of 2.5 mg/kg (P<0

  13. Glycogen-graft-poly(2-alkyl-2-oxazolines) - the new versatile biopolymer-based thermoresponsive macromolecular toolbox

    Czech Academy of Sciences Publication Activity Database

    Pospíšilová, Aneta; Filippov, Sergey K.; Bogomolova, Anna; Turner, S.; Sedláček, Ondřej; Matushkin, Nikolai; Černochová, Zulfiya; Štěpánek, Petr; Hrubý, Martin

    2014-01-01

    Roč. 4, č. 106 (2014), s. 61580-61588 ISSN 2046-2069 R&D Projects: GA ČR GA13-08336S; GA MŠk(CZ) LH14079 Grant - others:AV ČR(CZ) M200501201; AV ČR(CZ) ASCR/CONICET 2012CZ006 Program:M Institutional support: RVO:61389013 Keywords : glycogen * poly(2-alkyl-2-oxazoline) * hybrid copolymer Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.840, year: 2014

  14. Structure analysis of molecular systems in the Institute of Macromolecular Chemistry of the Czech Academy of Sciences

    Czech Academy of Sciences Publication Activity Database

    Hašek, Jindřich

    2010-01-01

    Roč. 17, 2a (2010), k32-k34 ISSN 1211-5894. [Struktura 2010. Soláň, 14.06.2010-17.06.2010] R&D Projects: GA AV ČR IAA500500701; GA ČR GA305/07/1073 Institutional research plan: CEZ:AV0Z40500505 Keywords : Academy of Sciences of the Czech Republic * X-ray structure analysis * crystallography Subject RIV: CD - Macromolecular Chemistry http:// xray .cz/ms/bul2010-2a/hasek.pdf

  15. Macromolecular crowding gives rise to microviscosity, anomalous diffusion and accelerated actin polymerization.

    Science.gov (United States)

    Rashid, Rafi; Chee, Stella Min Ling; Raghunath, Michael; Wohland, Thorsten

    2015-04-30

    Macromolecular crowding (MMC) has been used in various in vitro experimental systems to mimic in vivo physiology. This is because the crowded cytoplasm of cells contains many different types of solutes dissolved in an aqueous medium. MMC in the extracellular microenvironment is involved in maintaining stem cells in their undifferentiated state (niche) as well as in aiding their differentiation after they have travelled to new locations outside the niche. MMC at physiologically relevant fractional volume occupancies (FVOs) significantly enhances the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells during chemically induced adipogenesis. The mechanism by which MMC produces this enhancement is not entirely known. In the context of extracellular collagen deposition, we have recently reported the importance of optimizing the FVO while minimizing the bulk viscosity. Two opposing properties will determine the net rate of a biochemical reaction: the negative effect of bulk viscosity and the positive effect of the excluded volume, the latter being expressed by the FVO. In this study we have looked more closely at the effect of viscosity on reaction rates. We have used fluorimetry to measure the rate of actin polymerization and fluorescence correlation spectroscopy (FCS) to measure diffusion of various probes in solutions containing the crowder Ficoll at physiological concentrations. Similar to its effect on collagen, Ficoll enhanced the actin polymerization rate despite increasing the bulk viscosity. Our FCS measurements reveal a relatively minor component of anomalous diffusion. In addition, our measurements do suggest that microviscosity becomes relevant in a crowded environment. We ruled out bulk viscosity as a cause of the rate enhancement by performing the actin polymerization assay in glycerol. These opposite effects of Ficoll and glycerol led us to conclude that microviscosity becomes relevant at the length scale of the reacting

  16. Macromolecular crowding gives rise to microviscosity, anomalous diffusion and accelerated actin polymerization

    Science.gov (United States)

    Rashid, Rafi; Chee, Stella Min Ling; Raghunath, Michael; Wohland, Thorsten

    2015-05-01

    Macromolecular crowding (MMC) has been used in various in vitro experimental systems to mimic in vivo physiology. This is because the crowded cytoplasm of cells contains many different types of solutes dissolved in an aqueous medium. MMC in the extracellular microenvironment is involved in maintaining stem cells in their undifferentiated state (niche) as well as in aiding their differentiation after they have travelled to new locations outside the niche. MMC at physiologically relevant fractional volume occupancies (FVOs) significantly enhances the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells during chemically induced adipogenesis. The mechanism by which MMC produces this enhancement is not entirely known. In the context of extracellular collagen deposition, we have recently reported the importance of optimizing the FVO while minimizing the bulk viscosity. Two opposing properties will determine the net rate of a biochemical reaction: the negative effect of bulk viscosity and the positive effect of the excluded volume, the latter being expressed by the FVO. In this study we have looked more closely at the effect of viscosity on reaction rates. We have used fluorimetry to measure the rate of actin polymerization and fluorescence correlation spectroscopy (FCS) to measure diffusion of various probes in solutions containing the crowder Ficoll at physiological concentrations. Similar to its effect on collagen, Ficoll enhanced the actin polymerization rate despite increasing the bulk viscosity. Our FCS measurements reveal a relatively minor component of anomalous diffusion. In addition, our measurements do suggest that microviscosity becomes relevant in a crowded environment. We ruled out bulk viscosity as a cause of the rate enhancement by performing the actin polymerization assay in glycerol. These opposite effects of Ficoll and glycerol led us to conclude that microviscosity becomes relevant at the length scale of the reacting

  17. Leaching of organic acids from macromolecular organic matter by non-supercritical CO2

    Science.gov (United States)

    Sauer, P.; Glombitza, C.; Kallmeyer, J.

    2012-04-01

    The storage of CO2 in underground reservoirs is discussed controversly in the scientific literature. The worldwide search for suitable storage formations also considers coal-bearing strata. CO2 is already injected into seams for enhanced recovery of coal bed methane. However, the effects of increased CO2 concentration, especially on organic matter rich formations, are rarely investigated. The injected CO2 will dissolve in the pore water, causing a decrease in pH and resulting in acidic formation waters. Huge amounts of low molecular weight organic acids (LMWOAs) are chemically bound to the macromolecular matrix of sedimentary organic matter and may be liberated by hydrolysis, which is enhanced by the acidic porewater. Recent investigations outlined the importance of LMWOAs as a feedstock for microbial life in the subsurface [1]. Therefore, injection of CO2 into coal formations may result in enhanced nutrient supply for subsurface microbes. To investigate the effect of high concentrations of dissolved CO2 on the release of LMWOAs from coal we developed an inexpensive high-pressure high temperature system that allows manipulating the partial pressure of dissolved gases at pressures and temperatures up to 60 MPa and 120° C, respectively. In a reservoir vessel, gases are added to saturate the extraction medium to the desired level. Inside the extraction vessel hangs a flexible and inert PVDF sleeve (polyvinylidene fluoride, almost impermeable for gases), holding the sample and separating it from the pressure fluid. The flexibility of the sleeve allows for subsampling without loss of pressure. Coal samples from the DEBITS-1 well, Waikato Basin, NZ (R0 = 0.29, TOC = 30%). were extracted at 90° C and 5 MPa, either with pure or CO2-saturated water. Subsamples were taken at different time points during the extraction. The extracted LMWOAs such as formate, acetate and oxalate were analysed by ion chromatography. Yields of LMWOAs were higher with pure water than with CO2

  18. Photon-counting single-molecule spectroscopy for studying conformational dynamics and macromolecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Laurence, Ted Alfred [Univ. of California, Berkeley, CA (United States)

    2002-01-01

    Single-molecule methods have the potential to provide information about conformational dynamics and molecular interactions that cannot be obtained by other methods. Removal of ensemble averaging provides several benefits, including the ability to detect heterogeneous populations and the ability to observe asynchronous reactions. Single-molecule diffusion methodologies using fluorescence resonance energy transfer (FRET) are developed to monitor conformational dynamics while minimizing perturbations introduced by interactions between molecules and surfaces. These methods are used to perform studies of the folding of Chymotrypsin Inhibitor 2, a small, single-domain protein, and of single-stranded DNA (ssDNA) homopolymers. Confocal microscopy is used in combination with sensitive detectors to detect bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract fluorescence resonance energy transfer (FRET) efficiency. Advances in data acquisition and analysis techniques that are providing a more complete picture of the accessible molecular information are discussed. Photon Arrival-time Interval Distribution (PAID) analysis is a new method for monitoring macromolecular interactions by fluorescence detection with simultaneous determination of coincidence, brightness, diffusion time, and occupancy (proportional to concentration) of fluorescently-labeled molecules undergoing diffusion in a confocal detection volume. This method is based on recording the time of arrival of all detected photons, and then plotting the two-dimensional histogram of photon pairs, where one axis is the time interval between each pair of photons 1 and 2, and the second axis is the number of other photons detected in the time interval between photons 1 and 2. PAID is related to Fluorescence Correlation Spectroscopy (FCS) by a collapse of this histogram onto the time interval axis. PAID extends auto- and cross-correlation FCS

  19. Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Jenjob, Ratchapol [Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712 (Korea, Republic of); Kun, Na [Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743 (Korea, Republic of); Ghee, Jung Yeon [Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7–50, Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Shen, Zheyu; Wu, Xiaoxia [Division of Functional Materials and Nano-Devices, Ningbo Institute of Materials Technology & Engineering (NIMTE), Chinese Academy of Sciences, 519 Zhuangshi Street, Zhenhai District, Ningbo, Zhejiang 315201 (China); Cho, Steve K., E-mail: scho@gist.ac.kr [Division of Liberal Arts and Science, GIST College, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Lee, Don Haeng [Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7–50, Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Internal Medicine, School of Medicine, Inha University Hospital, Incheon 420-751 (Korea, Republic of); Yang, Su-Geun, E-mail: Sugeun.Yang@Inha.ac.kr [Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712 (Korea, Republic of)

    2016-04-01

    In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd{sup 3+}, chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd{sup 3+} in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd{sup 3+} incubated with Ca{sup 2+} was performed by using a dialysis membrane (MWCO 100–500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd{sup 3+}, the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd{sup 3+} were released from Gd-DTPA-Pullulan after 2 h incubation with Ca{sup 2+} and Fe{sup 2+}, respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t{sub 1/2,α} = 0.43 h, t{sub 1/2,β} = 2.32 h), much longer than 0.11 h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. - Highlights: • Macromolecule (pullulan) conjugated Gd contrast agent (Gd-DTPA-Pullulan) showed the extended plasma half-life (t{sub 1/2,α} = 0.43 h, t{sub 1/2,β} = 2.32 h) in comparison with Gd-EOB-DTPA • Gd-DTPA-pullulan T1 contrast agent exhibited strong chelation stability against Gd. • The extended blood circulation attributed the enhanced and prolonged MR contrast on abdominal region of rats. • The extended blood circulation may provide prolonged MR acquisition time window in clinics.

  20. Photon-counting single-molecule spectroscopy for studying conformational dynamics and macromolecular interactions

    International Nuclear Information System (INIS)

    Laurence, Ted Alfred

    2002-01-01

    Single-molecule methods have the potential to provide information about conformational dynamics and molecular interactions that cannot be obtained by other methods. Removal of ensemble averaging provides several benefits, including the ability to detect heterogeneous populations and the ability to observe asynchronous reactions. Single-molecule diffusion methodologies using fluorescence resonance energy transfer (FRET) are developed to monitor conformational dynamics while minimizing perturbations introduced by interactions between molecules and surfaces. These methods are used to perform studies of the folding of Chymotrypsin Inhibitor 2, a small, single-domain protein, and of single-stranded DNA (ssDNA) homopolymers. Confocal microscopy is used in combination with sensitive detectors to detect bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract fluorescence resonance energy transfer (FRET) efficiency. Advances in data acquisition and analysis techniques that are providing a more complete picture of the accessible molecular information are discussed. Photon Arrival-time Interval Distribution (PAID) analysis is a new method for monitoring macromolecular interactions by fluorescence detection with simultaneous determination of coincidence, brightness, diffusion time, and occupancy (proportional to concentration) of fluorescently-labeled molecules undergoing diffusion in a confocal detection volume. This method is based on recording the time of arrival of all detected photons, and then plotting the two-dimensional histogram of photon pairs, where one axis is the time interval between each pair of photons 1 and 2, and the second axis is the number of other photons detected in the time interval between photons 1 and 2. PAID is related to Fluorescence Correlation Spectroscopy (FCS) by a collapse of this histogram onto the time interval axis. PAID extends auto- and cross-correlation FCS

  1. Mineral Grains, Dimples, and Hot Volcanic Organic Streams: Dynamic Geological Backstage of Macromolecular Evolution.

    Science.gov (United States)

    Skoblikow, Nikolai E; Zimin, Andrei A

    2018-04-01

    , polycondensation, and formation of proto-cellular structures) are combined within a common dynamic geological process. We suppose macromolecular evolution had an extremely fast, "flash" start: the period from volcanic eruption to formation of lithocyte "populations" took not million years but just several tens of minutes. The scenario proposed can be verified experimentally with a three-module setup working with principles of dynamic (flow) chemistry in its core element.

  2. Identification of transcriptional macromolecular associations in human bone using browser based in silico analysis in a giant correlation matrix.

    Science.gov (United States)

    Reppe, Sjur; Sachse, Daniel; Olstad, Ole K; Gautvik, Vigdis T; Sanderson, Paul; Datta, Harish K; Berg, Jens P; Gautvik, Kaare M

    2013-03-01

    Intracellular signaling is critically dependent on gene regulatory networks comprising physical molecular interactions. Presently, there is a lack of comprehensive databases for most human tissue types to verify such macromolecular interactions. We present a user friendly browser which helps to identify functional macromolecular interactions in human bone as significant correlations at the transcriptional level. The molecular skeletal phenotype has been characterized by transcriptome analysis of iliac crest bone biopsies from 84 postmenopausal women through quantifications of ~23,000 mRNA species. When the signal levels were inter-correlated, an array containing >260 million correlations was generated, thus recognizing the human bone interactome at the RNA level. The matrix correlation and p values were made easily accessible by a freely available online browser. We show that significant correlations within the giant matrix are reproduced in a replica set of 13 male vertebral biopsies. The identified correlations differ somewhat from transcriptional interactions identified in cell culture experiments and transgenic mice, thus demonstrating that care should be taken in extrapolating such results to the in vivo situation in human bone. The current giant matrix and web browser are a valuable tool for easy access to the human bone transcriptome and molecular interactions represented as significant correlations at the RNA-level. The browser and matrix should be a valuable hypothesis generating tool for identification of regulatory mechanisms and serve as a library of transcript relationships in human bone, a relatively inaccessible tissue. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. AR-NE3A, a New Macromolecular Crystallography Beamline for Pharmaceutical Applications at the Photon Factory

    International Nuclear Information System (INIS)

    Yamada, Yusuke; Hiraki, Masahiko; Sasajima, Kumiko; Matsugaki, Naohiro; Igarashi, Noriyuki; Kikuchi, Takashi; Mori, Takeharu; Toyoshima, Akio; Kishimoto, Shunji; Wakatsuki, Soichi; Amano, Yasushi; Warizaya, Masaichi; Sakashita, Hitoshi

    2010-01-01

    Recent advances in high-throughput techniques for macromolecular crystallography have highlighted the importance of structure-based drug design (SBDD), and the demand for synchrotron use by pharmaceutical researchers has increased. Thus, in collaboration with Astellas Pharma Inc., we have constructed a new high-throughput macromolecular crystallography beamline, AR-NE3A, which is dedicated to SBDD. At AR-NE3A, a photon flux up to three times higher than those at existing high-throughput beams at the Photon Factory, AR-NW12A and BL-5A, can be realized at the same sample positions. Installed in the experimental hutch are a high-precision diffractometer, fast-readout, high-gain CCD detector, and sample exchange robot capable of handling more than two hundred cryo-cooled samples stored in a Dewar. To facilitate high-throughput data collection required for pharmaceutical research, fully automated data collection and processing systems have been developed. Thus, sample exchange, centering, data collection, and data processing are automatically carried out based on the user's pre-defined schedule. Although Astellas Pharma Inc. has a priority access to AR-NE3A, the remaining beam time is allocated to general academic and other industrial users.

  4. Implementation of fast macromolecular proton fraction mapping on 1.5 and 3 Tesla clinical MRI scanners: preliminary experience

    Science.gov (United States)

    Yarnykh, V.; Korostyshevskaya, A.

    2017-08-01

    Macromolecular proton fraction (MPF) is a biophysical parameter describing the amount of macromolecular protons involved into magnetization exchange with water protons in tissues. MPF represents a significant interest as a magnetic resonance imaging (MRI) biomarker of myelin for clinical applications. A recent fast MPF mapping method enabled clinical translation of MPF measurements due to time-efficient acquisition based on the single-point constrained fit algorithm. However, previous MPF mapping applications utilized only 3 Tesla MRI scanners and modified pulse sequences, which are not commonly available. This study aimed to test the feasibility of MPF mapping implementation on a 1.5 Tesla clinical scanner using standard manufacturer’s sequences and compare the performance of this method between 1.5 and 3 Tesla scanners. MPF mapping was implemented on 1.5 and 3 Tesla MRI units of one manufacturer with either optimized custom-written or standard product pulse sequences. Whole-brain three-dimensional MPF maps obtained from a single volunteer were compared between field strengths and implementation options. MPF maps demonstrated similar quality at both field strengths. MPF values in segmented brain tissues and specific anatomic regions appeared in close agreement. This experiment demonstrates the feasibility of fast MPF mapping using standard sequences on 1.5 T and 3 T clinical scanners.

  5. Evaluation of macromolecular electron-density map quality using the correlation of local r.m.s. density

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Berendzen, Joel

    1999-01-01

    The correlation of local r.m.s. density is shown to be a good measure of the presence of distinct solvent and macromolecule regions in macromolecular electron-density maps. It has recently been shown that the standard deviation of local r.m.s. electron density is a good indicator of the presence of distinct regions of solvent and protein in macromolecular electron-density maps [Terwilliger & Berendzen (1999 ▶). Acta Cryst. D55, 501–505]. Here, it is demonstrated that a complementary measure, the correlation of local r.m.s. density in adjacent regions on the unit cell, is also a good measure of the presence of distinct solvent and protein regions. The correlation of local r.m.s. density is essentially a measure of how contiguous the solvent (and protein) regions are in the electron-density map. This statistic can be calculated in real space or in reciprocal space and has potential uses in evaluation of heavy-atom solutions in the MIR and MAD methods as well as for evaluation of trial phase sets in ab initio phasing procedures

  6. Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina.

    Directory of Open Access Journals (Sweden)

    Sachin S Thakur

    Full Text Available Herein we showcase the potential of ultrasound-responsive nanobubbles in enhancing macromolecular permeation through layers of the retina, ultimately leading to significant and direct intracellular delivery; this being effectively demonstrated across three relevant and distinct retinal cell lines. Stably engineered nanobubbles of a highly homogenous and echogenic nature were fully characterised using dynamic light scattering, B-scan ultrasound and transmission electron microscopy (TEM. The nanobubbles appeared as spherical liposome-like structures under TEM, accompanied by an opaque luminal core and darkened corona around their periphery, with both features indicative of efficient gas entrapment and adsorption, respectively. A nanobubble +/- ultrasound sweeping study was conducted next, which determined the maximum tolerated dose for each cell line. Detection of underlying cellular stress was verified using the biomarker heat shock protein 70, measured before and after treatment with optimised ultrasound. Next, with safety to nanobubbles and optimised ultrasound demonstrated, each human or mouse-derived cell population was incubated with biotinylated rabbit-IgG in the presence and absence of ultrasound +/- nanobubbles. Intracellular delivery of antibody in each cell type was then quantified using Cy3-streptavidin. Nanobubbles and optimised ultrasound were found to be negligibly toxic across all cell lines tested. Macromolecular internalisation was achieved to significant, yet varying degrees in all three cell lines. The results of this study pave the way towards better understanding mechanisms underlying cellular responsiveness to ultrasound-triggered drug delivery in future ex vivo and in vivo models of the posterior eye.

  7. Indicators of Macromolecular Oxidative Damage and Antioxidant Defence Examinees Exposed to the Radar Frequencies 1.5 - 10.9 GHz

    International Nuclear Information System (INIS)

    Marjanovic, A.M.; Flajs, D.; Pavicic, I.; Domijan, A.

    2011-01-01

    Radar is an object-detection system which uses microwaves (Mw). As a result of increased use of radar there is a rising concern regarding health effects of Mw radiation on human body. Living organisms are complex electrochemical systems being evolved in a relatively narrow range of well-defined environmental parameters. For life to be maintained these parameters must be kept within their normal range, since deviations can induce biochemical effects causing cell function impairment and disease. Some theories indicate connection between Mw radiation, oxidative damage as well as antioxidant defence of organism. Aim of this study was to evaluate level and damage of macromolecular structures - proteins and lipids in blood of men occupationally exposed to Mw radiation. Concentration of glutathione (GSH), a known indicator of organism antioxidant defence, was also determined. Blood samples were collected from 27 male workers occupationally exposed to radar frequencies 1.5 to 10.9 GHz. Corresponding control group (N = 8) was a part of study. Concentrations of total and oxidised proteins, protein carbonyls, and GSH were measured by spectrophotometric method, while malondialdeyde (MDA), product of lipid peroxidation, was determined by high performance liquid chromatography (HPLC). Gained concentrations of oxidised proteins, GSH and MDA were presented in relation to total proteins. Concentration of oxidised proteins between control and exposed group of examinees did not show any significant statistical difference. However, concentration of GSH in exposed group was found considerably decreased, while concentration of MDA was found to be increased. Results indicate that Mw radiation of radar operating at frequencies 1.5 - 10.9 GHz could cause damage to proteins and lipids in addition to impairment of antioxidant defence of organism. (author)

  8. Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase.

    Science.gov (United States)

    Navarro, Gemma; Cordomí, Arnau; Casadó-Anguera, Verónica; Moreno, Estefanía; Cai, Ning-Sheng; Cortés, Antoni; Canela, Enric I; Dessauer, Carmen W; Casadó, Vicent; Pardo, Leonardo; Lluís, Carme; Ferré, Sergi

    2018-03-28

    G protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether the ligand-dependent interactions between these signaling molecules are based on random collisions or the rearrangement of pre-coupled elements in a macromolecular complex. Furthermore, it remains controversial whether a GPCR homodimer coupled to a single heterotrimeric G protein constitutes a common functional unit. Using a peptide-based approach, we here report evidence for the existence of functional pre-coupled complexes of heteromers of adenosine A 2A receptor and dopamine D 2 receptor homodimers coupled to their cognate Gs and Gi proteins and to subtype 5 AC. We also demonstrate that this macromolecular complex provides the necessary frame for the canonical Gs-Gi interactions at the AC level, sustaining the ability of a Gi-coupled GPCR to counteract AC activation mediated by a Gs-coupled GPCR.

  9. SASSIE: A program to study intrinsically disordered biological molecules and macromolecular ensembles using experimental scattering restraints

    Science.gov (United States)

    Curtis, Joseph E.; Raghunandan, Sindhu; Nanda, Hirsh; Krueger, Susan

    2012-02-01

    A program to construct ensembles of biomolecular structures that are consistent with experimental scattering data are described. Specifically, we generate an ensemble of biomolecular structures by varying sets of backbone dihedral angles that are then filtered using experimentally determined restraints to rapidly determine structures that have scattering profiles that are consistent with scattering data. We discuss an application of these tools to predict a set of structures for the HIV-1 Gag protein, an intrinsically disordered protein, that are consistent with small-angle neutron scattering experimental data. We have assembled these algorithms into a program called SASSIE for structure generation, visualization, and analysis of intrinsically disordered proteins and other macromolecular ensembles using neutron and X-ray scattering restraints. Program summaryProgram title: SASSIE Catalogue identifier: AEKL_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKL_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License v3 No. of lines in distributed program, including test data, etc.: 3 991 624 No. of bytes in distributed program, including test data, etc.: 826 Distribution format: tar.gz Programming language: Python, C/C++, Fortran Computer: PC/Mac Operating system: 32- and 64-bit Linux (Ubuntu 10.04, Centos 5.6) and Mac OS X (10.6.6) RAM: 1 GB Classification: 3 External routines: Python 2.6.5, numpy 1.4.0, swig 1.3.40, scipy 0.8.0, Gnuplot-py-1.8, Tcl 8.5, Tk 8.5, Mac installation requires aquaterm 1.0 (or X window system) and Xcode 3 development tools. Nature of problem: Open source software to generate structures of disordered biological molecules that subsequently allow for the comparison of computational and experimental results is limiting the use of scattering resources. Solution method: Starting with an all atom model of a protein, for example, users can input

  10. Liberation of microbial substrates from macromolecular organic matter by non-supercritical CO2

    Science.gov (United States)

    Sauer, P.; Glombitza, C.; Kallmeyer, J.

    2012-12-01

    The worldwide search for suitable underground storage formations for CO2 also considers coal-bearing strata. CO2 is already injected into coal seams for enhanced recovery of coal bed methane. However, the geochemical and microbiological effects of increased CO2 concentrations on organic matter rich formations are rarely investigated. The injected CO2 will dissolve in the pore water, causing a decrease in pH and resulting in acidic formation waters. Low molecular weight organic acids (LMWOAs) are chemically bound to the macromolecular matrix of sedimentary organic matter and may be liberated by hydrolysis, which is enhanced under acidic conditions. Recent investigations outlined the importance of LMWOAs as a feedstock for subsurface microbial life [1]. Therefore, injection of CO2 into coal formations may result in enhanced nutrient supply for subsurface microbes. To investigate the effects of highly CO2-saturated waters on the release of LMWOAs from coal, we developed an inexpensive high-pressure-high-temperature system that allows manipulating the concentration of dissolved gases up to 60 MPa and 120°C, respectively. The sample is placed in a flexible, gas-tight and inert PVDF sleeve, separating it from the pressure fluid and allowing for subsampling without loss of pressure. Lignite samples from the DEBITS-1 well, Waikato Basin, NZ and the Welzow-Süd open-cast mine, Niederlausitz, Germany, were extracted at 90° C and 5 MPa, with either pure water, CO2-saturated water, CO2/NO2 or CO2/SO2-saturated water. Subsamples were taken at different time points during the 72 hrs. long extraction. Extraction of LMWOAs from coal samples with our pressurised system resulted in yields that were up to four times higher than those reported for Soxhlet extraction [2]. These higher yields may be explained by the fact that during Soxhlet extraction the sample only gets into contact with freshly distilled water, whereas in our system the extraction fluid is circulated, resulting in

  11. Searching and Extracting Data from the EMBL-EBI Complex Portal.

    Science.gov (United States)

    Meldal, Birgit H M; Orchard, Sandra

    2018-01-01

    The Complex Portal ( www.ebi.ac.uk/complexportal ) is an encyclopedia of macromolecular complexes. Complexes are assigned unique, stable IDs, are species specific, and list all participating members with links to an appropriate reference database (UniProtKB, ChEBI, RNAcentral). Each complex is annotated extensively with its functions, properties, structure, stoichiometry, tissue expression profile, and subcellular location. Links to domain-specific databases allow the user to access additional information and enable data searching and filtering. Complexes can be saved and downloaded in PSI-MI XML, MI-JSON, and tab-delimited formats.

  12. Electrochemical Evidence of Host-Guest Interactions. Change of Redox Mechanism of Fungicides Iprodione and Procymidone in the Nano-cavity of Cyclodextrins

    Czech Academy of Sciences Publication Activity Database

    Hromadová, Magdaléna; Pospíšil, Lubomír; Giannarelli, S.; Fuoco, R.; Colombini, M. P.

    2002-01-01

    Roč. 73, - (2002), s. 213-219 ISSN 0026-265X R&D Projects: GA MŠk OC D15.10; GA ČR GP203/02/P082 Institutional research plan: CEZ:AV0Z4040901 Keywords : electrochemical evidence * fungicide * cyclodextrin Subject RIV: CG - Electrochemistry Impact factor: 1.325, year: 2002

  13. A facile and flexible process of β-cyclodextrin grafted on Fe3O4 magnetic nanoparticles and host-guest inclusion studies

    International Nuclear Information System (INIS)

    Zhu Jie; He Jiang; Du Xiaoyan; Lu Ruihua; Huang Lizhen; Ge Xia

    2011-01-01

    In this study, a kind of novel surface-functionalized magnetic nanoparticles was fabricated by the Fe 3 O 4 nanoparticles surface modification with mono-6-deoxy-6-(p-tolylsulfonyl)-cyclodextrin (6-TsO-β-CD), which were employed to interact with uric acid and their behavior was investigated by electrochemical methods. The architecture has been characterized by powder X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA), which confirmed that cyclodextrins have been effectively functionalized on the surface of Fe 3 O 4 nanoparticles. The analyses of vibration sample magnetometer (VSM) verified that the nanoparticles owned good magnetic property. The grafted β-cyclodextrin on the Fe3O4 nanoparticles contributed to as a modified electrode for detecting uric acid with cyclic voltammograms. Electrochemical results revealed that the new materials could exhibit excellent molecules recognition ability and show high electrochemical response. The new nanoparticles simultaneously had unique properties of magnetic nanoparticles and cyclodextrins through combining their individual distinct advantages.

  14. Flavylium network of chemical reactions in confined media: modulation of 3',4',7-trihydroxyflavilium reactions by host-guest interactions with cucurbit[7]uril.

    Science.gov (United States)

    Basílio, Nuno; Pina, Fernando

    2014-08-04

    In moderately acidic aqueous solutions, flavylium compounds undergo a pH-, and in some cases, light-dependent array of reversible chemical reactions. This network can be described as a single acid-base reaction involving a flavylium cation (acidic form) and a mixture of basic forms (quinoidal base, hemiketal and cis and trans chalcones). The apparent pK'a of the system and the relative mole fractions of the basic forms can be modulated by the interaction with cucurbit[7]uril. The system is studied by using (1) H NMR spectroscopy, UV/Vis spectroscopy, flash photolysis, and steady-state irradiation. Of all the network species, the flavylium cation possesses the highest affinity for cucurbit[7]uril. The rate of interconversion between flavylium cation and the basic species (where trans-chalcone is dominant) is approximately nine times lower inside the cucurbit[7]uril. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Quantitative analysis of the guest-concentration dependence of the mobility in a disordered fluorene-arylamine host-guest system in the guest-to-guest regime

    NARCIS (Netherlands)

    Nicolai, H. T.; Hof, A.J.; Lu, M.; Blom, P. W. M.; de Vries, R. J.; Coehoorn, R.

    2011-01-01

    The charge transport in a polyspirobifluorene derivative with copolymerized N,N,N',N'-tetraaryldiamino biphenyl (TAD) hole transport units is investigated as a function of the TAD content. For TAD concentrations larger than 5%, guest-to-guest transport is observed. It is demonstrated that in this

  16. Quantitative analysis of the guest-concentration dependence of the mobility in a disordered fluorene-arylamine host-guest system in the guest-to-guest regime

    NARCIS (Netherlands)

    Nicolai, H.T.; Hof, A.J.; Lu, M.; Blom, P.W.M.; Vries, R.J. de; Coehoorn, R.

    2011-01-01

    The charge transport in a polyspirobifluorene derivative with copolymerized N,N,N',N'-tetraaryldiamino biphenyl (TAD) hole transport units is investigated as a function of the TAD content. For TAD concentrations larger than 5, guest-to-guest transport is observed. It is demonstrated that in this

  17. Selective Surface Acoustic Wave-Based Organophosphorus Sensor Employing a Host-Guest Self-Assembly Monolayer of β-Cyclodextrin Derivative

    Directory of Open Access Journals (Sweden)

    Yong Pan

    2015-07-01

    Full Text Available Self-assembly and molecular imprinting technologies are very attractive technologies for the development of artificial recognition systems and provide chemical recognition based on need and not happenstance. In this paper, we employed a b-cyclodextrin derivative surface acoustic wave (SAW chemical sensor for detecting the chemical warfare agents (CWAs sarin (O-Isoprophyl methylphosphonofluoridate, GB. Using sarin acid (isoprophyl hydrogen methylphosphonate as an imprinting template, mono[6-deoxy-6-[(mercaptodecamethylenethio

  18. Metabolic growth rate control in Escherichia coli may be a consequence of subsaturation of the macromolecular biosynthetic apparatus with substrates and catalytic components

    DEFF Research Database (Denmark)

    Jensen, Kaj Frank; Pedersen, Steen

    1990-01-01

    In this paper, the Escherichia coli cell is considered as a system designed for rapid growth, but limited by the medium. We propose that this very design causes the cell to become subsaturated with precursors and catalytic components at all levels of macromolecular biosynthesis and leads to a mol...

  19. Errors in macromolecular synthesis after stress. A study of the possible protective role of the small heat shock proteinsBiochemistry

    NARCIS (Netherlands)

    Marin Vinader, L.

    2006-01-01

    The general goal of this thesis was to gain insight in what small heat shock proteins (sHsps) do with respect to macromolecular synthesis during a stressful situation in the cell. It is known that after a non-lethal heat shock, cells are better protected against a subsequent more severe heat shock,

  20. A fast band–Krylov eigensolver for macromolecular functional motion simulation on multicore architectures and graphics processors

    Energy Technology Data Exchange (ETDEWEB)

    Aliaga, José I., E-mail: aliaga@uji.es [Depto. Ingeniería y Ciencia de Computadores, Universitat Jaume I, Castellón (Spain); Alonso, Pedro [Departamento de Sistemas Informáticos y Computación, Universitat Politècnica de València (Spain); Badía, José M. [Depto. Ingeniería y Ciencia de Computadores, Universitat Jaume I, Castellón (Spain); Chacón, Pablo [Dept. Biological Chemical Physics, Rocasolano Physics and Chemistry Institute, CSIC, Madrid (Spain); Davidović, Davor [Rudjer Bošković Institute, Centar za Informatiku i Računarstvo – CIR, Zagreb (Croatia); López-Blanco, José R. [Dept. Biological Chemical Physics, Rocasolano Physics and Chemistry Institute, CSIC, Madrid (Spain); Quintana-Ortí, Enrique S. [Depto. Ingeniería y Ciencia de Computadores, Universitat Jaume I, Castellón (Spain)

    2016-03-15

    We introduce a new iterative Krylov subspace-based eigensolver for the simulation of macromolecular motions on desktop multithreaded platforms equipped with multicore processors and, possibly, a graphics accelerator (GPU). The method consists of two stages, with the original problem first reduced into a simpler band-structured form by means of a high-performance compute-intensive procedure. This is followed by a memory-intensive but low-cost Krylov iteration, which is off-loaded to be computed on the GPU by means of an efficient data-parallel kernel. The experimental results reveal the performance of the new eigensolver. Concretely, when applied to the simulation of macromolecules with a few thousands degrees of freedom and the number of eigenpairs to be computed is small to moderate, the new solver outperforms other methods implemented as part of high-performance numerical linear algebra packages for multithreaded architectures.

  1. A new on-axis multimode spectrometer for the macromolecular crystallography beamlines of the Swiss Light Source

    International Nuclear Information System (INIS)

    Owen, Robin L.; Pearson, Arwen R.; Meents, Alke; Boehler, Pirmin; Thominet, Vincent; Schulze-Briese, Clemens

    2009-01-01

    Complementary techniques greatly aid the interpretation of macromolecule structures to yield functional information, and can also help to track radiation-induced changes. A new on-axis spectrometer being integrated into the macromolecular crystallography beamlines of the Swiss Light Source is presented. X-ray crystallography at third-generation synchrotron sources permits tremendous insight into the three-dimensional structure of macromolecules. Additional information is, however, often required to aid the transition from structure to function. In situ spectroscopic methods such as UV–Vis absorption and (resonance) Raman can provide this, and can also provide a means of detecting X-ray-induced changes. Here, preliminary results are introduced from an on-axis UV–Vis absorption and Raman multimode spectrometer currently being integrated into the beamline environment at X10SA of the Swiss Light Source. The continuing development of the spectrometer is also outlined

  2. A fast band–Krylov eigensolver for macromolecular functional motion simulation on multicore architectures and graphics processors

    International Nuclear Information System (INIS)

    Aliaga, José I.; Alonso, Pedro; Badía, José M.; Chacón, Pablo; Davidović, Davor; López-Blanco, José R.; Quintana-Ortí, Enrique S.

    2016-01-01

    We introduce a new iterative Krylov subspace-based eigensolver for the simulation of macromolecular motions on desktop multithreaded platforms equipped with multicore processors and, possibly, a graphics accelerator (GPU). The method consists of two stages, with the original problem first reduced into a simpler band-structured form by means of a high-performance compute-intensive procedure. This is followed by a memory-intensive but low-cost Krylov iteration, which is off-loaded to be computed on the GPU by means of an efficient data-parallel kernel. The experimental results reveal the performance of the new eigensolver. Concretely, when applied to the simulation of macromolecules with a few thousands degrees of freedom and the number of eigenpairs to be computed is small to moderate, the new solver outperforms other methods implemented as part of high-performance numerical linear algebra packages for multithreaded architectures.

  3. Polyelectrolyte complex formation and stability when mixing polyanions and polycations in salted media: A model study related to the case of body fluids

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Leclercq, L.; Boustta, M.; Vert, M.

    2005-01-01

    Roč. 25, 1-2 (2005), s. 281-288 ISSN 0928-0987 EU Projects: European Commission(XE) 512087 - GIANT Institutional research plan: CEZ:AV0Z40500505 Keywords : polyelectrolyte complex * selectivity * light scattering Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.347, year: 2005

  4. Complexation of the cesium cation with 1,3-alternate-25,27-bis(1-octyloxy)calix[4]arene-crown-6

    Czech Academy of Sciences Publication Activity Database

    Makrlík, E.; Dybal, Jiří; Vaňura, P.

    2013-01-01

    Roč. 295, č. 2 (2013), s. 1299-1303 ISSN 0236-5731 R&D Projects: GA ČR GA203/09/1478 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : cesium cation * substituted calix[4]arene-crown-6 * complexation Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.415, year: 2013

  5. A neutral polydisulfide containing Gd(III) DOTA monoamide as a redox-sensitive biodegradable macromolecular MRI contrast agent.

    Science.gov (United States)

    Ye, Zhen; Zhou, Zhuxian; Ayat, Nadia; Wu, Xueming; Jin, Erlei; Shi, Xiaoyue; Lu, Zheng-Rong

    2016-01-01

    This work aims to develop safe and effective gadolinium (III)-based biodegradable macromolecular MRI contrast agents for blood pool and cancer imaging. A neutral polydisulfide containing macrocyclic Gd-DOTA monoamide (GOLS) was synthesized and characterized. In addition to studying the in vitro degradation of GOLS, its kinetic stability was also investigated in an in vivo model. The efficacy of GOLS for contrast-enhanced MRI was examined with female BALB/c mice bearing 4T1 breast cancer xenografts. The pharmacokinetics, biodistribution, and metabolism of GOLS were also determined in mice. GOLS has an apparent molecular weight of 23.0 kDa with T1 relaxivities of 7.20 mM(-1) s(-1) per Gd at 1.5 T, and 6.62 mM(-1) s(-1) at 7.0 T. GOLS had high kinetic inertness against transmetallation with Zn(2+) ions, and its polymer backbone was readily cleaved by L-cysteine. The agent showed improved efficacy for blood pool and tumor MR imaging. The structural effect on biodistribution and in vivo chelation stability was assessed by comparing GOLS with Gd(HP-DO3A), a negatively charged polydisulfide containing Gd-DOTA monoamide GODC, and a polydisulfide containing Gd-DTPA-bisamide (GDCC). GOLS showed high in vivo chelation stability and minimal tissue deposition of gadolinium. The biodegradable macromolecular contrast agent GOLS is a promising polymeric contrast agent for clinical MR cardiovascular imaging and cancer imaging. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Macromolecular Engineering: New Routes Towards the Synthesis of Well-??Defined Polyethers/Polyesters Co/Terpolymers with Different Architectures

    KAUST Repository

    Alamri, Haleema

    2016-05-18

    The primary objective of this research was to develop a new and efficient pathway for well-defined multicomponent homo/co/terpolymers of cyclic esters/ethers using an organocatalytic approach with an emphasis on the macromolecular engineering aspects of the overall synthesis. Macromolecular engineering (as discussed in the first chapter) of homo/copolymers refers to the specific tailoring of these materials for achieving an easy and reproducible synthesis that results in precise molecular characteristics, i.e. molecular weight and polydispersity, as well as specific structure and end?group choices. Precise control of these molecular characteristics will provide access to new materials that can be used for pre-targeted purposes such as biomedical applications. Among the most commonly used engineering materials are polyesters (biocompatible and biodegradable) and polyethers (biocompatible), either as homopolymers or when or copolymers with linear structures. The ability to create non-linear structures, for example stars, will open new horizons in the applications of these important polymeric materials. The second part of this thesis describes the synthesis of aliphatic polyesters, particularly polycaprolactone and polylactide, using a metal-free initiator/catalyst system. A phosphazene base (t?BuP2) was used as the catalyst for the ring-opening copolymerization of ?-aprolactone (??CL) and L,Lactide (LLA) at room temperature with a variety of protic initiators in different solvents. These studies provided important information for the design of a metal-free route toward the synthesis of polyester?based (bio) materials. The third part of the thesis describes a novel route for the one?pot synthesis of polyether-b polyester block copolymers with either a linear or a specific macromolecular architecture. Poly (styrene oxide)?b?poly(caprolactone)?b?poly(L,lactide) was prepared using this method with the goal of synthesizing poly(styrene oxide)-based materials since this

  7. Synthesis and biological evaluation of novel folic acid receptor-targeted, β-cyclodextrin-based drug complexes for cancer treatment.

    Directory of Open Access Journals (Sweden)

    Juan-Juan Yin

    Full Text Available Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+] cancer. Water-soluble folic acid (FA-conjugated CD carriers (FACDs were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR, matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS, high performance liquid chromatography (HPLC, Fourier transform infrared spectroscopy (FTIR, and circular dichroism. Drug complexes of adamatane (Ada and cytotoxic doxorubicin (Dox with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5-2.5 nm. The host-guest association constant K a was 1,639 M(-1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+ cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release

  8. The In-Situ One-Step Synthesis of a PDC Macromolecular Pro-Drug and the Fabrication of a Novel Core-Shell Micell.

    Science.gov (United States)

    Yu, Cui-Yun; Yang, Sa; Li, Zhi-Ping; Huang, Can; Ning, Qian; Huang, Wen; Yang, Wen-Tong; He, Dongxiu; Sun, Lichun

    2016-01-01

    The development of slow release nano-sized carriers for efficient antineoplastic drug delivery with a biocompatible and biodegradable pectin-based macromolecular pro-drug for tumor therapy has been reported in this study. Pectin-doxorubicin conjugates (PDC), a macromolecular pro-drug, were prepared via an amide condensation reaction, and a novel amphiphilic core-shell micell based on a PDC macromolecular pro-drug (PDC-M) was self-assembled in situ, with pectin as the hydrophilic shell and doxorubicin (DOX) as the hydrophobic core. Then the chemical structure of the PDC macromolecular pro-drug was identified by both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ((1)H-NMR), and proved that doxorubicin combined well with the pectin and formed macromolecular pro-drug. The PDC-M were observed to have an unregularly spherical shape and were uniform in size by scanning electron microscopy (SEM). The average particle size of PDC-M, further measured by a Zetasizer nanoparticle analyzer (Nano ZS, Malvern Instruments), was about 140 nm. The encapsulation efficiency and drug loading were 57.82% ± 3.7% (n = 3) and 23.852% ±2.3% (n = 3), respectively. The in vitro drug release behaviors of the resulting PDC-M were studied in a simulated tumor environment (pH 5.0), blood (pH 7.4) and a lysosome media (pH 6.8), and showed a prolonged slow release profile. Assays for antiproliferative effects and flow cytometry of the resulting PDC-M in HepG2 cell lines demonstrated greater properties of delayed and slow release as compared to free DOX. A cell viability study against endothelial cells further revealed that the resulting PDC-M possesses excellent cell compatibilities and low cytotoxicities in comparison with that of the free DOX. Hemolysis activity was investigated in rabbits, and the results also demonstrated that the PDC-M has greater compatibility in comparison with free DOX. This shows that the resulting PDC-M can ameliorate the

  9. Moessbauer spectroscopic characterization of macromolecule-metallochlorophyll complexes

    International Nuclear Information System (INIS)

    Inoue, H.; Fukuda, K.; Nonomura, Y.; Fluck, E.

    1993-01-01

    The bis-adducts of iron chlorophylls with poly(4-vinylpyridine-costyrene) (PVP) have been prepared and characterized by 57 Fe Moessbauer spectroscopy. The Moessbauer parameters of the PVP-adducts of iron chlorophylls are typical of low-spin iron(II) complexes. The central iron(III) ion is spontaneously reduced upon the axial coordination of PVP to iron(III) chlorophylls. The general tendency in the spontaneous reduction of the iron(III) chlorophylls has been interpreted in terms of the σ-donor and π-acceptor power of the axial macromolecular ligand. (orig.)

  10. Macromolecular HPMA-based nanoparticles with cholesterol for solid-tumor targeting: detailed study of the inner structure of a highly efficient drug delivery system

    Czech Academy of Sciences Publication Activity Database

    Filippov, Sergey K.; Chytil, Petr; Konarev, P. V.; Dyakonova, M.; Papadakis, C. M.; Zhigunov, Alexander; Pleštil, Josef; Štěpánek, Petr; Etrych, Tomáš; Ulbrich, Karel; Svergun, D. I.

    2012-01-01

    Roč. 13, č. 8 (2012), s. 2594-2604 ISSN 1525-7797 R&D Projects: GA MŠk ME09059; GA AV ČR IAAX00500803; GA ČR GAP108/12/0640 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : HPMA * cholesterol * SAXS Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.371, year: 2012

  11. Macromolecular 3D SEM reconstruction strategies: Signal to noise ratio and resolution

    International Nuclear Information System (INIS)

    Woodward, J.D.; Wepf, R.A.

    2014-01-01

    Three-dimensional scanning electron microscopy generates quantitative volumetric structural data from SEM images of macromolecules. This technique provides a quick and easy way to define the quaternary structure and handedness of protein complexes. Here, we apply a variety of preparation and imaging methods to filamentous actin in order to explore the relationship between resolution, signal-to-noise ratio, structural preservation and dataset size. This information can be used to define successful imaging strategies for different applications. - Highlights: • F-actin SEM datasets were collected using 8 different preparation/ imaging techniques. • Datasets were reconstructed by back projection and compared/analyzed • 3DSEM actin reconstructions can be produced with <100 views of the asymmetric unit. • Negatively stained macromolecules can be reconstructed by 3DSEM to ∼3 nm resolution

  12. Fluorene-based macromolecular nanostructures and nanomaterials for organic (opto)electronics.

    Science.gov (United States)

    Xie, Ling-Hai; Yang, Su-Hui; Lin, Jin-Yi; Yi, Ming-Dong; Huang, Wei

    2013-10-13

    Nanotechnology not only opens up the realm of nanoelectronics and nanophotonics, but also upgrades organic thin-film electronics and optoelectronics. In this review, we introduce polymer semiconductors and plastic electronics briefly, followed by various top-down and bottom-up nano approaches to organic electronics. Subsequently, we highlight the progress in polyfluorene-based nanoparticles and nanowires (nanofibres), their tunable optoelectronic properties as well as their applications in polymer light-emitting devices, solar cells, field-effect transistors, photodetectors, lasers, optical waveguides and others. Finally, an outlook is given with regard to four-element complex devices via organic nanotechnology and molecular manufacturing that will spread to areas such as organic mechatronics in the framework of robotic-directed science and technology.

  13. Synthesis and evaluation of water-soluble poly(vinyl alcohol)-paclitaxel conjugate as a macromolecular prodrug

    International Nuclear Information System (INIS)

    Kakinoki, Atsufumi; Kaneo, Yoshiharu; Tanaka, Tetsuro; Hosokawa, Yoshitsugu

    2008-01-01

    Paclitaxel (PTX) is an antitumor agent for the treatment of various human cancers. Cremophor EL and ethanol are used to formulate PTX in commercial injection solutions, because of its poor solubility in water. However, these agents cause severe allergic reaction upon intravenous administration. The aim of this study is to synthesize water-soluble macromolecular prodrugs of PTX for enhancing the therapeutic efficacy. Poly (vinyl alcohol) (PVA, 80 kDa), water-soluble synthetic polymer, was used as a drug carrier which is safe and stable in the body. The 2'-hydroxyl group of PTX was reacted with succinic anhydride and then carboxylic group of the succinyl spacer was coupled to PVA via ethylene diamine spacer, resulting the water-soluble prodrug of poly (vinyl alcohol)-paclitaxel conjugate (PVA-SPTX). The solubility of PTX was greatly enhanced by the conjugation to PVA. The release of PTX from the conjugate was accelerated at the neutral to basic conditions in in vitro release experiment. [ 125 I]-labeled PVA-SPTX was retained in the blood circulation for several days and was gradually distributed into the tumorous tissue after intravenous injection to the tumor-bearing mice. PVA-SPTX inhibited the growth of sarcoma 180 cells subcutaneously inoculated in mice. It was suggested that the water-solubility of PTX was markedly enhanced by the conjugation to PVA, and PVA-SPTX effectively delivered PTX to the tumorous tissue due to the enhanced permeability and retention (EPR) effect. (author)

  14. Innovative High-Throughput SAXS Methodologies Based on Photonic Lab-on-a-Chip Sensors: Application to Macromolecular Studies.

    Science.gov (United States)

    Rodríguez-Ruiz, Isaac; Radajewski, Dimitri; Charton, Sophie; Phamvan, Nhat; Brennich, Martha; Pernot, Petra; Bonneté, Françoise; Teychené, Sébastien

    2017-06-02

    The relevance of coupling droplet-based Photonic Lab-on-a-Chip (PhLoC) platforms and Small-Angle X-Ray Scattering (SAXS) technique is here highlighted for the performance of high throughput investigations, related to the study of protein macromolecular interactions. With this configuration, minute amounts of sample are required to obtain reliable statistical data. The PhLoC platforms presented in this work are designed to allow and control an effective mixing of precise amounts of proteins, crystallization reagents and buffer in nanoliter volumes, and the subsequent generation of nanodroplets by means of a two-phase flow. Spectrophotometric sensing permits a fine control on droplet generation frequency and stability as well as on concentration conditions, and finally the droplet flow is synchronized to perform synchrotron radiation SAXS measurements in individual droplets (each one acting as an isolated microreactor) to probe protein interactions. With this configuration, droplet physic-chemical conditions can be reproducibly and finely tuned, and monitored without cross-contamination, allowing for the screening of a substantial number of saturation conditions with a small amount of biological material. The setup was tested and validated using lysozyme as a model of study. By means of SAXS experiments, the proteins gyration radius and structure envelope were calculated as a function of protein concentration. The obtained values were found to be in good agreement with previously reported data, but with a dramatic reduction of sample volume requirements compared to studies reported in the literature.

  15. Accelerated Development of Supramolecular Corneal Stromal-Like Assemblies from Corneal Fibroblasts in the Presence of Macromolecular Crowders.

    Science.gov (United States)

    Kumar, Pramod; Satyam, Abhigyan; Fan, Xingliang; Rochev, Yury; Rodriguez, Brian J; Gorelov, Alexander; Joshi, Lokesh; Raghunath, Michael; Pandit, Abhay; Zeugolis, Dimitrios I

    2015-07-01

    Tissue engineering by self-assembly uses the cells' secretome as a regeneration template and biological factory of trophic factors. Despite the several advantages that have been witnessed in preclinical and clinical settings, the major obstacle for wide acceptance of this technology remains the tardy extracellular matrix formation. In this study, we assessed the influence of macromolecular crowding (MMC)/excluding volume effect, a biophysical phenomenon that accelerates thermodynamic activities and biological processes by several orders of magnitude, in human corneal fibroblast (HCF) culture. Our data indicate that the addition of negatively charged galactose derivative (carrageenan) in HCF culture, even at 0.5% serum, increases by 12-fold tissue-specific matrix deposition, while maintaining physiological cell morphology and protein/gene expression. Gene analysis indicates that a glucose derivative (dextran sulfate) may drive corneal fibroblasts toward a myofibroblast lineage. Collectively, these results indicate that MMC may be suitable not only for clinical translation and commercialization of tissue engineering by self-assembly therapies, but also for the development of in vitro pathophysiology models.

  16. New insight on aliphatic linkages in the macromolecular organic fraction of Orgueil and Murchison meteorites through ruthenium tetroxide oxidation

    Science.gov (United States)

    Remusat, Laurent; Derenne, Sylvie; Robert, François

    2005-09-01

    Ruthenium tetroxide oxidation was used to examine the macromolecular insoluble organic matter (IOM) from the Orgueil and Murchison meteorites and especially to characterize the aliphatic linkages. Already applied to various terrestrial samples, ruthenium tetroxide is a selective oxidant which destroys aromatic units, converting them into CO 2, and yields aliphatic and aromatic acids. In our experiment on chondritic IOM, it produces mainly short aliphatic diacids and polycarboxylic aromatic acids. Some short hydroxyacids are also detected. Aliphatic diacids are interpreted as aliphatic bridges between aromatic units in the chemical structure, and polycarboxylic aromatic acids are the result of the fusion of polyaromatic units. The product distribution shows that aliphatic links are short with numerous substitutions. No indigenous monocarboxylic acid was detected, showing that free aliphatic chains must be very short (less than three carbon atoms). The hydroxyacids are related to the occurrence of ester and ether functional groups within the aliphatic bridges between the aromatic units. This technique thus allows us to characterize in detail the aliphatic linkages of the IOMs, and the derived conclusions are in agreement with spectroscopic, pyrolytic, and degradative results previously reported. Compared to terrestrial samples, the aliphatic part of chondritic IOM is shorter and highly substituted. Aromatic units are smaller and more cross-linked than in coals, as already proposed from NMR data. Orgueil and Murchison IOM exhibit some tiny differences, especially in the length of aliphatic chains.

  17. Effects of nicotine on cellular proliferation, cell cycle phase distribution, and macromolecular synthesis in human promyelocytic HL-60 leukaemia cells

    International Nuclear Information System (INIS)

    Konno, S.; Wu, J.M.; Chiao, J.W.

    1986-01-01

    Addition of nicotine causes a dose- and time-dependent inhibition of cell growth in the human promyelocytic HL-60 leukemia cells, with 4 mM nicotine resulting in a 50% inhibition of cellular proliferation after 48-50h. Accompanying the anticellular effect of nicotine is a significant change in the cell cycle distribution of HL-60 cells. For example, treatment with 4 mM nicotine for 20h causes an increase in the proportion of G1-phase cells (from 49% to 57%) and a significant decrease in the proportion of S-phase cells (from 41% to 32%). These results suggest that nicotine causes partial cell arrest in the G-1 phase which may in part account for its effects on cell growth. To determine whether nicotine changes the cellular uptake/transport to macromolecular precursors, HL-60 cells were treated with 216 mM nicotine for 30h, at the end of which time cells were labelled with ( 3 H)thymidine, ( 3 H)uridine, ( 14 C)lysine and( 35 S)methionine, the trichloroacetic acid soluble and insoluble radioactivities from each of the labelling conditions were determined. These studies show that nicotine mainly affects the ''de novo synthesis'' of proteins. (author)

  18. Determination of macromolecular exchange and PO2 in the microcirculation: a simple system for in vivo fluorescence and phosphorescence videomicroscopy

    Directory of Open Access Journals (Sweden)

    Torres L.N.

    2001-01-01

    Full Text Available We have developed a system with two epi-illumination sources, a DC-regulated lamp for transillumination and mechanical switches for rapid shift of illumination and detection of defined areas (250-750 µm² by fluorescence and phosphorescence videomicroscopy. The system permits investigation of standard microvascular parameters, vascular permeability as well as intra- and extravascular PO2 by phosphorescence quenching of Pd-meso-tetra (4-carboxyphenyl porphine (PORPH. A Pechan prism was used to position a defined region over the photomultiplier and TV camera. In order to validate the system for in vivo use, in vitro tests were performed with probes at concentrations that can be found in microvascular studies. Extensive in vitro evaluations were performed by filling glass capillaries with solutions of various concentrations of FITC-dextran (diluted in blood and in saline mixed with different amounts of PORPH. Fluorescence intensity and phosphorescence decay were determined for each mixture. FITC-dextran solutions without PORPH and PORPH solutions without FITC-dextran were used as references. Phosphorescence decay curves were relatively unaffected by the presence of FITC-dextran at all concentrations tested (0.1 µg/ml to 5 mg/ml. Likewise, fluorescence determinations were performed in the presence of PORPH (0.05 to 0.5 mg/ml. The system was successfully used to study macromolecular extravasation and PO2 in the rat mesentery circulation under controlled conditions and during ischemia-reperfusion.

  19. Macromolecular Design Strategies for Preventing Active-Material Crossover in Non-Aqueous All-Organic Redox-Flow Batteries.

    Science.gov (United States)

    Doris, Sean E; Ward, Ashleigh L; Baskin, Artem; Frischmann, Peter D; Gavvalapalli, Nagarjuna; Chénard, Etienne; Sevov, Christo S; Prendergast, David; Moore, Jeffrey S; Helms, Brett A

    2017-02-01

    Intermittent energy sources, including solar and wind, require scalable, low-cost, multi-hour energy storage solutions in order to be effectively incorporated into the grid. All-Organic non-aqueous redox-flow batteries offer a solution, but suffer from rapid capacity fade and low Coulombic efficiency due to the high permeability of redox-active species across the battery's membrane. Here we show that active-species crossover is arrested by scaling the membrane's pore size to molecular dimensions and in turn increasing the size of the active material above the membrane's pore-size exclusion limit. When oligomeric redox-active organics (RAOs) were paired with microporous polymer membranes, the rate of active-material crossover was reduced more than 9000-fold compared to traditional separators at minimal cost to ionic conductivity. This corresponds to an absolute rate of RAO crossover of less than 3 μmol cm -2  day -1 (for a 1.0 m concentration gradient), which exceeds performance targets recently set forth by the battery industry. This strategy was generalizable to both high and low-potential RAOs in a variety of non-aqueous electrolytes, highlighting the versatility of macromolecular design in implementing next-generation redox-flow batteries. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

    Science.gov (United States)

    Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

    2017-01-01

    Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P<0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM−1 s−1) was observed compared to Magnevist® (4.9 mM−1 s−1; P<0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. PMID:28765707

  1. Macromolecular Colloids of Diblock Poly(amino acids) That Bind Insulin.

    Science.gov (United States)

    Constancis; Meyrueix; Bryson; Huille; Grosselin; Gulik-Krzywicki; Soula

    1999-09-15

    The diblock polymer poly(l-leucine-block-l-glutamate), bLE, was synthesized by acid hydrolysis of the ester poly(l-leucine-block-l-methyl glutamate). During the hydrolysis reaction the leucine block precipitates from the reaction mixture, forming nanosized particulate structures. These particles can be purified and further suspended in water or in 0.15 M phosphate saline buffer (PBS) to give stable, colloidal dispersions. TEM analysis shows the predominant particle form to be that of platelets with a diameter of 200 nm. Smaller cylindrical or spherical particles form a relatively minor fraction of the sample. After fractionation, analysis shows the platelets to be compositionally rich in leucine, while the spheres are glutamate-rich. (1)H NMR, CD, and X-ray diffraction indicate that the core of the platelets is composed of crystalline, helical leucine segments. The poly(l-glutamate) polyelectrolyte brush extending out from the two faces of the disk stabilizes individual particles from flocculation. At pH 7.4, the nanoparticles (platelets and cylinders) spontaneously adsorb proteins, such as insulin, directly from solution. Partial desorption of the protein in its native configuration can be induced by simple dilution. The reversibility of the insulin-nanoparticle complex is the basis for a potential new delivery system. Copyright 1999 Academic Press.

  2. Self-assembling supramolecular systems of different symmetry formed by wedged macromolecular dendrons

    Energy Technology Data Exchange (ETDEWEB)

    Shcherbina, M. A., E-mail: shcherbina@ispm.ru; Bakirov, A. V. [Russian Academy of Sciences, Institute of Synthetic Polymer Materials (Russian Federation); Yakunin, A. N. [Karpov Institute of Physical Chemistry (Russian Federation); Percec, V. [University of Pennsylvania (United States); Beginn, U. [Universitaet Osnabrueck, Institut fuer Chemie (Germany); Moeller, M. [Institute for Technical and Macromolecular Chemistry (Germany); Chvalun, S. N. [Russian Academy of Sciences, Institute of Synthetic Polymer Materials (Russian Federation)

    2012-03-15

    The main stages of the self-assembling of supramolecular ensembles have been revealed by studying different functional wedged macromolecules: polymethacrylates with tapered side chains based on gallic acid, their macromonomers, and salts of 2,3,4- and 3,4,5-tris(dodecyloxy)benzenesulphonic acid. The first stage is the formation of individual supramolecular aggregates (long cylinders or spherical micelles) due to the weak noncovalent interactions of mesogenic groups and the subsequent ordering in these aggregates, which is accompanied by a decrease in the free energy of the system. Supramolecular aggregates, in turn, form 2D or 3D lattices. The shape of supramolecular aggregates and its change with temperature are delicate functions of the mesogen chemical structure; this circumstance makes it possible to rationally design complex self-assembling systems with the ability to respond smartly to external stimuli. X-ray diffraction analysis allows one to study the structure of supramolecular systems with different degrees of order, determine the type of mesophases formed by these systems, and reveal the phase behavior of the material. Particular attention has been paid to the method for reconstruction of electron density distribution from the relative reflection intensity. The application of a suite of experimental methods, including wide- and small-angle X-ray diffraction, molecular modeling, differential scanning calorimetry, and polarization optical microscopy, allows one to establish the relationship between the shape of the structural unit (molecule or molecular aggregate), the nature of the interaction, and the phase behavior of the material.

  3. Self-assembling supramolecular systems of different symmetry formed by wedged macromolecular dendrons

    International Nuclear Information System (INIS)

    Shcherbina, M. A.; Bakirov, A. V.; Yakunin, A. N.; Percec, V.; Beginn, U.; Möller, M.; Chvalun, S. N.

    2012-01-01

    The main stages of the self-assembling of supramolecular ensembles have been revealed by studying different functional wedged macromolecules: polymethacrylates with tapered side chains based on gallic acid, their macromonomers, and salts of 2,3,4- and 3,4,5-tris(dodecyloxy)benzenesulphonic acid. The first stage is the formation of individual supramolecular aggregates (long cylinders or spherical micelles) due to the weak noncovalent interactions of mesogenic groups and the subsequent ordering in these aggregates, which is accompanied by a decrease in the free energy of the system. Supramolecular aggregates, in turn, form 2D or 3D lattices. The shape of supramolecular aggregates and its change with temperature are delicate functions of the mesogen chemical structure; this circumstance makes it possible to rationally design complex self-assembling systems with the ability to respond smartly to external stimuli. X-ray diffraction analysis allows one to study the structure of supramolecular systems with different degrees of order, determine the type of mesophases formed by these systems, and reveal the phase behavior of the material. Particular attention has been paid to the method for reconstruction of electron density distribution from the relative reflection intensity. The application of a suite of experimental methods, including wide- and small-angle X-ray diffraction, molecular modeling, differential scanning calorimetry, and polarization optical microscopy, allows one to establish the relationship between the shape of the structural unit (molecule or molecular aggregate), the nature of the interaction, and the phase behavior of the material.

  4. Teaching structure: student use of software tools for understanding macromolecular structure in an undergraduate biochemistry course.

    Science.gov (United States)

    Jaswal, Sheila S; O'Hara, Patricia B; Williamson, Patrick L; Springer, Amy L

    2013-01-01

    Because understanding the structure of biological macromolecules is critical to understanding their function, students of biochemistry should become familiar not only with viewing, but also with generating and manipulating structural representations. We report a strategy from a one-semester undergraduate biochemistry course to integrate use of structural representation tools into both laboratory and homework activities. First, early in the course we introduce the use of readily available open-source software for visualizing protein structure, coincident with modules on amino acid and peptide bond properties. Second, we use these same software tools in lectures and incorporate images and other structure representations in homework tasks. Third, we require a capstone project in which teams of students examine a protein-nucleic acid complex and then use the software tools to illustrate for their classmates the salient features of the structure, relating how the structure helps explain biological function. To ensure engagement with a range of software and database features, we generated a detailed template file that can be used to explore any structure, and that guides students through specific applications of many of the software tools. In presentations, students demonstrate that they are successfully interpreting structural information, and using representations to illustrate particular points relevant to function. Thus, over the semester students integrate information about structural features of biological macromolecules into the larger discussion of the chemical basis of function. Together these assignments provide an accessible introduction to structural representation tools, allowing students to add these methods to their biochemical toolboxes early in their scientific development. © 2013 by The International Union of Biochemistry and Molecular Biology.

  5. FlexED8: the first member of a fast and flexible sample-changer family for macromolecular crystallography.

    Science.gov (United States)

    Papp, Gergely; Felisaz, Franck; Sorez, Clement; Lopez-Marrero, Marcos; Janocha, Robert; Manjasetty, Babu; Gobbo, Alexandre; Belrhali, Hassan; Bowler, Matthew W; Cipriani, Florent

    2017-10-01

    Automated sample changers are now standard equipment for modern macromolecular crystallography synchrotron beamlines. Nevertheless, most are only compatible with a single type of sample holder and puck. Recent work aimed at reducing sample-handling efforts and crystal-alignment times at beamlines has resulted in a new generation of compact and precise sample holders for cryocrystallography: miniSPINE and NewPin [see the companion paper by Papp et al. (2017, Acta Cryst., D73, 829-840)]. With full data collection now possible within seconds at most advanced beamlines, and future fourth-generation synchrotron sources promising to extract data in a few tens of milliseconds, the time taken to mount and centre a sample is rate-limiting. In this context, a versatile and fast sample changer, FlexED8, has been developed that is compatible with the highly successful SPINE sample holder and with the miniSPINE and NewPin sample holders. Based on a six-axis industrial robot, FlexED8 is equipped with a tool changer and includes a novel open sample-storage dewar with a built-in ice-filtering system. With seven versatile puck slots, it can hold up to 112 SPINE sample holders in uni-pucks, or 252 miniSPINE or NewPin sample holders, with 36 samples per puck. Additionally, a double gripper, compatible with the SPINE sample holders and uni-pucks, allows a reduction in the sample-exchange time from 40 s, the typical time with a standard single gripper, to less than 5 s. Computer vision-based sample-transfer monitoring, sophisticated error handling and automatic error-recovery procedures ensure high reliability. The FlexED8 sample changer has been successfully tested under real conditions on a beamline.

  6. iDC: A comprehensive toolkit for the analysis of residual dipolar couplings for macromolecular structure determination

    International Nuclear Information System (INIS)

    Wei Yufeng; Werner, Milton H.

    2006-01-01

    Measurement of residual dipolar couplings (RDCs) has become an important method for the determination and validation of protein or nucleic acid structures by NMRf spectroscopy. A number of toolkits have been devised for the handling of RDC data which run in the Linux/Unix operating environment and require specifically formatted input files. The outputs from these programs, while informative, require format modification prior to the incorporation of this data into commonly used personal computer programs for manuscript preparation. To bridge the gap between analysis and publication, an easy-to-use, comprehensive toolkit for RDC analysis has been created, iDC. iDC is written for the WaveMetrics Igor Pro mathematics program, a widely used graphing and data analysis software program that runs on both Windows PC and Mac OS X computers. Experimental RDC values can be loaded into iDC using simple data formats accessible to Igor's tabular data function. The program can perform most useful RDC analyses, including alignment tensor estimation from a histogram of RDC occurrence versus values and order tensor analysis by singular value decomposition (SVD). SVD analysis can be performed on an entire structure family at once, a feature missing in other applications of this kind. iDC can also import from and export to several different commonly used programs for the analysis of RDC data (DC, PALES, REDCAT) and can prepare formatted files for RDC-based refinement of macromolecular structures using XPLOR-NIH, CNS and ARIA. The graphical user interface provides an easy-to-use I/O for data, structures and formatted outputs

  7. Macromolecular 'size' and 'hardness' drives structure in solvent-swollen blends of linear, cyclic, and star polymers.

    Science.gov (United States)

    Gartner, Thomas E; Jayaraman, Arthi

    2018-01-17

    In this paper, we apply molecular simulation and liquid state theory to uncover the structure and thermodynamics of homopolymer blends of the same chemistry and varying chain architecture in the presence of explicit solvent species. We use hybrid Monte Carlo (MC)/molecular dynamics (MD) simulations in the Gibbs ensemble to study the swelling of ∼12 000 g mol -1 linear, cyclic, and 4-arm star polystyrene chains in toluene. Our simulations show that the macroscopic swelling response is indistinguishable between the various architectures and matches published experimental data for the solvent annealing of linear polystyrene by toluene vapor. We then use standard MD simulations in the NPT ensemble along with polymer reference interaction site model (PRISM) theory to calculate effective polymer-solvent and polymer-polymer Flory-Huggins interaction parameters (χ eff ) in these systems. As seen in the macroscopic swelling results, there are no significant differences in the polymer-solvent and polymer-polymer χ eff between the various architectures. Despite similar macroscopic swelling and effective interaction parameters between various architectures, the pair correlation function between chain centers-of-mass indicates stronger correlations between cyclic or star chains in the linear-cyclic blends and linear-star blends, compared to linear chain-linear chain correlations. Furthermore, we note striking similarities in the chain-level correlations and the radius of gyration of cyclic and 4-arm star architectures of identical molecular weight. Our results indicate that the cyclic and star chains are 'smaller' and 'harder' than their linear counterparts, and through comparison with MD simulations of blends of soft spheres with varying hardness and size we suggest that these macromolecular characteristics are the source of the stronger cyclic-cyclic and star-star correlations.

  8. Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

    Directory of Open Access Journals (Sweden)

    Liu YJ

    2017-07-01

    Full Text Available Yongjun Liu,1 Xiaoyun Wu,1 Xiaohe Sun,1 Dan Wang,1 Ying Zhong,1 Dandan Jiang,1 Tianqi Wang,1 Dexin Yu,2 Na Zhang1 1School of Pharmaceutical Science, Shandong University, 2Department of Radiology Medicine, Qilu Hospital, Jinan, People’s Republic of China Abstract: Developing magnetic resonance imaging (MRI contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR-targeted poly (l-lysine (PLL-diethylene triamine pentacetate acid (DTPA-gadolinium (Gd (VEGFR-targeted PLL-DTPA-Gd, VPDG, was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22% in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG (25.16%±4.71%, P<0.05. In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM-1 s-1 was observed compared to Magnevist® (4.9 mM-1 s-1; P<0.01. Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h. These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. Keywords: MRI, contrast agent, VEGFR, biotin–avidin reaction, relaxivity

  9. Characterization of macromolecular baseline of human brain using metabolite cycled semi-LASER at 9.4T.

    Science.gov (United States)

    Giapitzakis, Ioannis-Angelos; Avdievich, Nikolai; Henning, Anke

    2018-08-01

    Macromolecular resonances (MM) arise mainly from cytosolic proteins and overlap with metabolites, influencing metabolite quantification. Macromolecules can serve as valuable biomarkers for diseases and pathologies. The objectives of this study were to characterize MM at 9.4T in the human brain (occipital and left parietal lobe) and to describe the RF coil setup used for MM acquisition in the two regions. An adiabatic inversion pulse was optimised for metabolite nulling at 9.4T using double inversion recovery and was combined for the first time with metabolite cycled (MC) semi-LASER and appropriate coil configuration. MM spectra (seven volunteers) from two brain locations were averaged and smoothed creating MM templates, which were then parametrized using simulated Voigt-shaped lines within LCModel. Quantification was performed on individual data sets, including corrections for different tissue composition and the T 1 and T 2 relaxation of water. Our coil configuration method resulted in efficient B1+ (>30 T/√kW) for both brain regions. The 15 MM components were detected and quantified in MM baselines of the two brain areas. No significant differences in concentration levels of MM between different regions were found. Two new MM peaks were reported (M7 & M8). Double inversion, which was combined with MC semi-LASER, enabled the acquisition of high spectral resolution MM spectra for both brain regions at 9.4T. The 15 MM components were detected and quantified. Two new MM peaks were reported for the first time (M7 & M8) and preliminarily assigned to β-methylene protons of aspartyl-groups. Magn Reson Med 80:462-473, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

  10. Computations between metallocalix(4)arene host and a series of four oil-based fuel pollutant guests

    International Nuclear Information System (INIS)

    Pathak, D.A.; Street, N.C.

    2006-01-01

    Calculations using PM3 and mechanics methods on metallocalix(4)arene hosts (1-10) and substituted dibenzothiophene guests (A-D), which are generally known as oil-based fuel pollutants, show that host-guest formation is energetically favored. Calculations have been carried out for both 1/1 and 1/4 ratios of host/guest. There is no direct bonding between the metal center of the host and the sulfur of the guest in the host-guest complex. Sterically hundered dibenzothiophene guests show similar energies to the unhindered analogs. For calix(4)arenas (5-10) in partial cone conformations and having hydrogen rather than p-tert-butyl groups on the wide rim, host-guest formation occurs within the narrow rim rather than the wide rim. Host-guest association appears to occur via Pie-Pie interactions between host and guest phenyl groups rather than via metal-sulfur bonding. The study has importance especially in oil refining to obtain environmentally safe fuel oils and help supramolecular chemists in designing and synthesizing more sophisticated host molecules for the removal of sulfur from crude oil / refinery oil. (author)

  11. Complexity explained

    CERN Document Server

    Erdi, Peter

    2008-01-01

    This book explains why complex systems research is important in understanding the structure, function and dynamics of complex natural and social phenomena. Readers will learn the basic concepts and methods of complex system research.

  12. Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA chromatin remodeling complexes.

    Science.gov (United States)

    Lee, Kenneth K; Sardiu, Mihaela E; Swanson, Selene K; Gilmore, Joshua M; Torok, Michael; Grant, Patrick A; Florens, Laurence; Workman, Jerry L; Washburn, Michael P

    2011-07-05

    Despite the availability of several large-scale proteomics studies aiming to identify protein interactions on a global scale, little is known about how proteins interact and are organized within macromolecular complexes. Here, we describe a technique that consists of a combination of biochemistry approaches, quantitative proteomics and computational methods using wild-type and deletion strains to investigate the organization of proteins within macromolecular protein complexes. We applied this technique to determine the organization of two well-studied complexes, Spt-Ada-Gcn5 histone acetyltransferase (SAGA) and ADA, for which no comprehensive high-resolution structures exist. This approach revealed that SAGA/ADA is composed of five distinct functional modules, which can persist separately. Furthermore, we identified a novel subunit of the ADA complex, termed Ahc2, and characterized Sgf29 as an ADA family protein present in all Gcn5 histone acetyltransferase complexes. Finally, we propose a model for the architecture of the SAGA and ADA complexes, which predicts novel functional associations within the SAGA complex and provides mechanistic insights into phenotypical observations in SAGA mutants.

  13. Calixarene receptors in the selective separation of alachlor. Characterization of the separated complexes

    International Nuclear Information System (INIS)

    Garcia G, M.C.

    2004-01-01

    in dilute as concentrate solutions, solvents as chloroform and acetonitrile did not interfere in the formation of the species. At the same time and based on the structure of the reactants and information from the scientific literature related to this particular topic, using the M M3, CONFLEX and MOPAC/PM5/COSMO procedures, we calculated the optimized geometry which rendered the most stable molecular structures of reactants and products, this means those with the lowest minimum energies, the lowest energies of the most stable conformers and the heat of formation of the most stable conformational structures of the calixarene-substrate species. The latter were those formed by hydrogen bonding and π-π interactions. Species formed with H n bL n stabilized by hydrogen bonding through CH 2 -Cl interaction of alachlor with OH groups of the calixarenes. Concerning the phosphinoylated calixarenes, the P=O groups immobilize the alachlor by hydrogen bonding with the benzyl of the acetanilide. However, the species formed with alachlor and parents or functionalized calixarenes demanded a second interaction between calixarene phenyl-π-π-benzyl-alachlor to be stabilised. Heat of formation of reactants and products allowed to calculate the heat o reaction associated to the formation of the hosts...guest species, these results were surprising in line with the experimental results. Based on the solution and computational results we synthesized and isolated the calixarene---alachlor complexes in sizeable amounts. The latter were characterized by spectroscopic techniques like IR, UV-Vis, luminescence and elemental analysis. The results from the solution and solid studies of the reagents and products as molar absorption coefficients, the features of the luminescence and IR spectra, luminescence lifetimes and minimum formulae of the isolated complexes are in good agreement with the parameters and tendencies of the minimum energies of the geometrical and conformational structures found

  14. Complex chemistry

    International Nuclear Information System (INIS)

    Kim, Bong Gon; Kim, Jae Sang; Kim, Jin Eun; Lee, Boo Yeon

    2006-06-01

    This book introduces complex chemistry with ten chapters, which include development of complex chemistry on history coordination theory and Warner's coordination theory and new development of complex chemistry, nomenclature on complex with conception and define, chemical formula on coordination compound, symbol of stereochemistry, stereo structure and isomerism, electron structure and bond theory on complex, structure of complex like NMR and XAFS, balance and reaction on solution, an organo-metallic chemistry, biology inorganic chemistry, material chemistry of complex, design of complex and calculation chemistry.

  15. From precision polymers to complex materials and systems

    Science.gov (United States)

    Lutz, Jean-François; Lehn, Jean-Marie; Meijer, E. W.; Matyjaszewski, Krzysztof

    2016-05-01

    Complex chemical systems, such as living biological matter, are highly organized structures based on discrete molecules in constant dynamic interactions. These natural materials can evolve and adapt to their environment. By contrast, man-made materials exhibit simpler properties. In this Review, we highlight that most of the necessary elements for the development of more complex synthetic matter are available today. Using modern strategies, such as controlled radical polymerizations, supramolecular polymerizations or stepwise synthesis, polymers with precisely controlled molecular structures can be synthesized. Moreover, such tailored polymers can be folded or self-assembled into defined nanoscale morphologies. These self-organized macromolecular objects can be at thermal equilibrium or can be driven out of equilibrium. Recently, in the latter case, interesting dynamic materials have been developed. However, this is just a start, and more complex adaptive materials are anticipated.

  16. A gadolinium(III) complex of a carboxylic-phosphorus acid derivative of diethylenetriamine covalently bound to inulin, a potential macromolecular MRI contrast agent.

    Science.gov (United States)

    Lebdusková, Petra; Kotek, Jan; Hermann, Petr; Vander Elst, Luce; Muller, Robert N; Lukes, Ivan; Peters, Joop A

    2004-01-01

    A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as contrast agent for magnetic resonance imaging (MRI) was synthesized. The structure of the chelate was derived from H5DTPA by replacing the central pendant arm by a phosphinic acid functional group, which was covalently bound to the polysaccharide inulin. On the average, each monosaccharide unit of the inulin was attached to approximately one (0.9) chelate moiety. The average molecular weight is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate oxygen atoms, and one P-O oxygen atom, and its first coordination sphere is completed by a water molecule. This compound shows promising properties for application as a contrast agent for MRI thanks to a favorable residence lifetime of this water molecule (170 ns at 298 K), a relatively long rotational correlation time (866 ps at 298 K), and the presence of two water molecules in the second coordination sphere of the Gd3+ ion. Furthermore, its stability toward transmetalation with Zn(II) is as high as that of the clinically used [Gd(DTPA)(H2O)]2-.

  17. Complexation between Methyl Viologen (Paraquat) Bis(Hexafluorophosphate) and Dibenzo[24]Crown-8 Revisited

    DEFF Research Database (Denmark)

    Gasa, Travis B.; Spruell, Jason M.; Dichtel, William R.

    2009-01-01

    Paraquat bis(hexafluorophosphate) undergoes stepwise dissociation in acetone. All three species - the neutral molecule, and the mono- and dications - are represented significantly under the experimental conditions typically used in host-guest binding studies. Paraquat forms at least four host...... toward dibenzo[24]crown-8. Thus, the relative abundance of neutral, singly, and doubly charged pseudorotaxanes is identical to the relative abundance of neutral, singly, and doubly charged paraquat unbound with respect to the crown ether in acetone. In the specific case of paraquat/dibenzo[24]crown-8...

  18. Identification of the Mitochondrial Heme Metabolism Complex.

    Science.gov (United States)

    Medlock, Amy E; Shiferaw, Mesafint T; Marcero, Jason R; Vashisht, Ajay A; Wohlschlegel, James A; Phillips, John D; Dailey, Harry A

    2015-01-01

    Heme is an essential cofactor for most organisms and all metazoans. While the individual enzymes involved in synthesis and utilization of heme are fairly well known, less is known about the intracellular trafficking of porphyrins and heme, or regulation of heme biosynthesis via protein complexes. To better understand this process we have undertaken a study of macromolecular assemblies associated with heme synthesis. Herein we have utilized mass spectrometry with coimmunoprecipitation of tagged enzymes of the heme biosynthetic pathway in a developing erythroid cell culture model to identify putative protein partners. The validity of these data obtained in the tagged protein system is confirmed by normal porphyrin/heme production by the engineered cells. Data obtained are consistent with the presence of a mitochondrial heme metabolism complex which minimally consists of ferrochelatase, protoporphyrinogen oxidase and aminolevulinic acid synthase-2. Additional proteins involved in iron and intermediary metabolism as well as mitochondrial transporters were identified as potential partners in this complex. The data are consistent with the known location of protein components and support a model of transient protein-protein interactions within a dynamic protein complex.

  19. Chiral Recognition in Molecular and Macromolecular Pairs of(S)- and (R)- 1-Cyano-2-Methylpropyl 4’((4-(8-Vinyloxyoctyloxy)Benzoyl) Biphenyl-4-Carboxylate Enantiomers

    Science.gov (United States)

    1994-06-30

    above please provide a graphical abstract of the paper ar, return it to the Editorial Office as soon as possible. 4oeg0 o F-99S or TS A& I DTI•’ I J. u1...TCLSICAON 2.LIMITATION OF ABSTRAC •F oFPORT OF THIS PAGE OF ABSTRACT . unclass ified Graphical Abstracts for Perkin Txans. 1 Example TITLE GRAPHICAL ... ABSTRACT AUTHORS’ N AMES Template (S)-II Chiral recognition in molecular and . -- macromolecular pairs of (S)- and -- (R)-i-cyano-2-methyipropyl 4’-{[4

  20. A simple model for solvation in mixed solvents. Applications to the stabilization and destabilization of macromolecular structures.

    Science.gov (United States)

    Schellman, J A

    1990-08-31

    The properties of a simple model for solvation in mixed solvents are explored in this paper. The model is based on the supposition that solvent replacement is a simple one-for-one substitution reaction at macromolecular sites which are independent of one another. This leads to a new form for the binding polynomial in which all terms are associated with ligand interchange rather than ligand addition. The principal solvent acts as one of the ligands. Thermodynamic analysis then shows that thermodynamic binding (i.e., selective interaction) depends on the properties of K'-1, whereas stoichiometric binding (site occupation) depends on K'. K' is a 'practical' interchange equilibrium constant given by (f3/f1)K, where K is the true equilibrium constant for the interchange of components 3 and 1 on the site and f3 and f4 denote their respective activity coefficients on the mole fraction scale. Values of K' less than unity lead to negative selective interaction. It is selective interaction and not occupation number which determines the thermodynamic effects of solvation. When K' greater than 100 on the mole fraction scale or K' greater than 2 on the molality scale (in water), the differences between stoichiometric binding and selective interaction become less than 1%. The theory of this paper is therefore necessary only for very weak binding constants. When K'-1 is small, large concentrations of the added solvent component are required to produce a thermodynamic effect. Under these circumstances the isotherms for the selective interaction and for the excess (or transfer) free energy are strongly dependent on the behavior of the activity coefficients of both solvent components. Two classes of behavior are described depending on whether the components display positive or negative deviations from Raoult's law. Examples which are discussed are aqueous solutions of urea and guanidinium chloride for positive deviations and of sucrose and glucose for negative deviations

  1. Synthesis, structure, and properties of a series of chiral tweezer-diamine complexes consisting of an achiral zinc(II) bisporphyrin host and chiral diamine guest: induction and rationalization of supramolecular chirality.

    Science.gov (United States)

    Brahma, Sanfaori; Ikbal, Sk Asif; Rath, Sankar Prasad

    2014-01-06

    We report here the synthesis, structure, and spectroscopic properties of a series of supramolecular chiral 1:1 tweezer-diamine complexes consisting of an achiral Zn(II) bisporphyrin (Zn2DPO) host and five different chiral diamine guests, namely, (R)-diaminopropane (DAP), (1S,2S)-diaminocyclohexane (CHDA), (S)-phenylpropane diamine (PPDA), (S)-phenyl ethylenediamine (PEDA), and (1R,2R)-diphenylethylene diamine (DPEA). The solid-state structures are preserved in solution, as reflected in their (1)H NMR spectra, which also revealed the remarkably large upfield shifts of the NH2 guest protons with the order Zn2DPO·DAP > Zn2DPO·CHDA > Zn2DPO·PPDA> Zn2DPO·PEDA ≫ Zn2DPO·DPEA, which happens to be the order of binding constants of the respective diamines with Zn2DPO. As the bulk of the substituent at the chiral center of the guest ligand increases, the Zn-Nax distance of the tweezer-diamine complex also increases, which eventually lowers the binding of the guest ligand toward the host. Also, the angle between the two porphyrin rings gradually increases with increasing bulk of the guest in order to accommodate the guest within the bisporphyrin cavity with minimal steric clash. The notably high amplitude bisignate CD signal response by Zn2DPO·DAP, Zn2DPO·CHDA, and Zn2DPO·PPDA can be ascribed to the complex's high stability and the formation of a unidirectional screw as observed in the X-ray structures of the complexes. A relatively lower value of CD amplitude shown by Zn2DPO·PEDA is due to the lower stability of the complex. The projection of the diamine binding sites of the chiral guest would make the two porphyrin macrocycles oriented in either a clockwise or anticlockwise direction in order to minimize host-guest steric clash. In sharp contrast, Zn2DPO·DPEA shows a very low amplitude bisignate CD signal due to the presence of both left- (dictated by the pre-existing chirality of (1R,2R)-DPEA) and right-handed screws (dictated by the steric differentiation at

  2. High Performance Macromolecular Material

    National Research Council Canada - National Science Library

    Forest, M

    2002-01-01

    .... In essence, most commercial high-performance polymers are processed through fiber spinning, following Nature and spider silk, which is still pound-for-pound the toughest liquid crystalline polymer...

  3. Subunit Organisation of In Vitro Reconstituted HOPS and CORVET Multisubunit Membrane Tethering Complexes

    Science.gov (United States)

    Guo, Zhong; Johnston, Wayne; Kovtun, Oleksiy; Mureev, Sergey; Bröcker, Cornelia; Ungermann, Christian; Alexandrov, Kirill

    2013-01-01

    Biochemical and structural analysis of macromolecular protein assemblies remains challenging due to technical difficulties in recombinant expression, engineering and reconstitution of multisubunit complexes. Here we use a recently developed cell-free protein expression system based on the protozoan Leishmania tarentolae to produce in vitro all six subunits of the 600 kDa HOPS and CORVET membrane tethering complexes. We demonstrate that both subcomplexes and the entire HOPS complex can be reconstituted in vitro resulting in a comprehensive subunit interaction map. To our knowledge this is the largest eukaryotic protein complex in vitro reconstituted to date. Using the truncation and interaction analysis, we demonstrate that the complex is assembled through short hydrophobic sequences located in the C-terminus of the individual Vps subunits. Based on this data we propose a model of the HOPS and CORVET complex assembly that reconciles the available biochemical and structural data. PMID:24312556

  4. Subsumed complexity: abiogenesis as a by-product of complex energy transduction

    Science.gov (United States)

    Adam, Z. R.; Zubarev, D.; Aono, M.; Cleaves, H. James

    2017-11-01

    The origins of life bring into stark relief the inadequacy of our current synthesis of thermodynamic, chemical, physical and information theory to predict the conditions under which complex, living states of organic matter can arise. Origins research has traditionally proceeded under an array of implicit or explicit guiding principles in lieu of a universal formalism for abiogenesis. Within the framework of a new guiding principle for prebiotic chemistry called subsumed complexity, organic compounds are viewed as by-products of energy transduction phenomena at different scales (subatomic, atomic, molecular and polymeric) that retain energy in the form of bonds that inhibit energy from reaching the ground state. There is evidence for an emergent level of complexity that is overlooked in most conceptualizations of abiogenesis that arises from populations of compounds formed from atomic energy input. We posit that different forms of energy input can exhibit different degrees of dissipation complexity within an identical chemical medium. By extension, the maximum capacity for organic chemical complexification across molecular and macromolecular scales subsumes, rather than emerges from, the underlying complexity of energy transduction processes that drive their production and modification. This article is part of the themed issue 'Reconceptualizing the origins of life'.

  5. Manipulation of Energy Transfer Processes in Nano channels

    International Nuclear Information System (INIS)

    Devaux, A.; Calzaferri, G.

    2010-01-01

    The realisation of molecular assemblies featuring specific macroscopic properties is a prime example for the versatility of supramolecular organisation. Microporous materials such as zeolite L are well suited for the preparation of host-guest composites containing dyes, complexes, or clusters. This short tutorial focuses on the possibilities offered by zeolite L to study and influence Forster resonance energy transfer inside of its nano channels. The highly organised host-guest materials can in turn be structured on a larger scale to form macroscopic patterns, making it possible to create large-scale structures from small, highly organised building blocks for novel optical applications.

  6. Energy transfer in a mechanically trapped exciplex.

    Science.gov (United States)

    Klosterman, Jeremy K; Iwamura, Munetaka; Tahara, Tahei; Fujita, Makoto

    2009-07-15

    Host-guest complexes involving M(6)L(4) coordination cages can display unusual photoreactivity, and enclathration of the very large fluorophore bisanthracene resulted in an emissive, mechanically trapped intramolecular exciplex. Mechanically linked intramolecular exciplexes are important for understanding the dependence of energy transfer on donor-acceptor distance, orientation, and electronic coupling but are relatively unexplored. Steady-state and picosecond time-resolved fluorescence measurements have revealed that selective excitation of the encapsulated guest fluorophore results in efficient energy transfer from the excited guest to an emissive host-guest exciplex state.

  7. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  8. Vertical Distributions of Macromolecular Composition of Particulate Organic Matter in the Water Column of the Amundsen Sea Polynya During the Summer in 2014

    Science.gov (United States)

    Kim, Bo Kyung; Lee, SangHoon; Ha, Sun-Yong; Jung, Jinyoung; Kim, Tae Wan; Yang, Eun Jin; Jo, Naeun; Lim, Yu Jeong; Park, Jisoo; Lee, Sang Heon

    2018-02-01

    Macromolecular compositions (carbohydrates, proteins, and lipids) of particulate organic matter (POM) are crucial as a basic marine food quality. To date, however, one investigation has been carried out in the Amundsen Sea. Water samples for macromolecular compositions were obtained at selected seven stations in the Amundsen Sea Polynya (AP) during the austral summer in 2014 to investigate vertical characteristics of POM. We found that a high proportion of carbohydrates (45.9 ± 11.4%) in photic layer which are significantly different from the previous result (27.9 ± 6.9%) in the AP, 2012. The plausible reason could be the carbohydrate content strongly associated with biomass of the dominant species (Phaeocystis antarctica). The calorific content of food material (FM) in the photic layer obtained in this study is similar with that of the Ross Sea as one of the highest primary productivity regions in the Southern Ocean. Total concentrations, calorific values, and calorific contents of FM were higher in the photic layer than the aphotic layer, which implies that a significant fraction of organic matter underwent degradation. A decreasing proteins/carbohydrates (PRT/CHO) ratio with depth could be caused by preferential nitrogen loss during sinking period. Since the biochemical compositions of POM mostly fixed in photic layers could play an important role in transporting organic carbon into the deep sea, further detail studies on the variations in biochemical compositions and main controlling factors are needed to understand sinking mechanisms of POM.

  9. Stretchable All-Gel-State Fiber-Shaped Supercapacitors Enabled by Macromolecularly Interconnected 3D Graphene/Nanostructured Conductive Polymer Hydrogels.

    Science.gov (United States)

    Li, Panpan; Jin, Zhaoyu; Peng, Lele; Zhao, Fei; Xiao, Dan; Jin, Yong; Yu, Guihua

    2018-05-01

    Nanostructured conductive polymer hydrogels (CPHs) have been extensively applied in energy storage owing to their advantageous features, such as excellent electrochemical activity and relatively high electrical conductivity, yet the fabrication of self-standing and flexible electrode-based CPHs is still hampered by their limited mechanical properties. Herein, macromolecularly interconnected 3D graphene/nanostructured CPH is synthesized via self-assembly of CPHs and graphene oxide macrostructures. The 3D hybrid hydrogel shows uniform interconnectivity and enhanced mechanical properties due to the strong macromolecular interaction between the CPHs and graphene, thus greatly reducing aggregation in the fiber-shaping process. A proof-of-concept all-gel-state fibrous supercapacitor based on the 3D polyaniline/graphene hydrogel is fabricated to demonstrate the outstanding flexibility and mouldability, as well as superior electrochemical properties enabled by this 3D hybrid hydrogel design. The proposed device can achieve a large strain (up to ≈40%), and deliver a remarkable volumetric energy density of 8.80 mWh cm -3 (at power density of 30.77 mW cm -3 ), outperforming many fiber-shaped supercapacitors reported previously. The all-hydrogel design opens up opportunities in the fabrication of next-generation wearable and portable electronics. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. A new on-axis micro-spectrophotometer for combining Raman, fluorescence and UV/Vis absorption spectroscopy with macromolecular crystallography at the Swiss Light Source

    International Nuclear Information System (INIS)

    Pompidor, Guillaume; Dworkowski, Florian S. N.; Thominet, Vincent; Schulze-Briese, Clemens; Fuchs, Martin R.

    2013-01-01

    The new version MS2 of the in situ on-axis micro-spectrophotometer at the macromolecular crystallography beamline X10SA of the Swiss Light Source supports the concurrent acquisition of Raman, resonance Raman, fluorescence and UV/Vis absorption spectra along with diffraction data. The combination of X-ray diffraction experiments with optical methods such as Raman, UV/Vis absorption and fluorescence spectroscopy greatly enhances and complements the specificity of the obtained information. The upgraded version of the in situ on-axis micro-spectrophotometer, MS2, at the macromolecular crystallography beamline X10SA of the Swiss Light Source is presented. The instrument newly supports Raman and resonance Raman spectroscopy, in addition to the previously available UV/Vis absorption and fluorescence modes. With the recent upgrades of the spectral bandwidth, instrument stability, detection efficiency and control software, the application range of the instrument and its ease of operation were greatly improved. Its on-axis geometry with collinear X-ray and optical axes to ensure optimal control of the overlap of sample volumes probed by each technique is still unique amongst comparable facilities worldwide and the instrument has now been in general user operation for over two years

  11. Accurate macromolecular crystallographic refinement: incorporation of the linear scaling, semiempirical quantum-mechanics program DivCon into the PHENIX refinement package

    Energy Technology Data Exchange (ETDEWEB)

    Borbulevych, Oleg Y.; Plumley, Joshua A.; Martin, Roger I. [QuantumBio Inc., 2790 West College Avenue, State College, PA 16801 (United States); Merz, Kenneth M. Jr [University of Florida, Gainesville, Florida (United States); Westerhoff, Lance M., E-mail: lance@quantumbioinc.com [QuantumBio Inc., 2790 West College Avenue, State College, PA 16801 (United States)

    2014-05-01

    Semiempirical quantum-chemical X-ray macromolecular refinement using the program DivCon integrated with PHENIX is described. Macromolecular crystallographic refinement relies on sometimes dubious stereochemical restraints and rudimentary energy functionals to ensure the correct geometry of the model of the macromolecule and any covalently bound ligand(s). The ligand stereochemical restraint file (CIF) requires a priori understanding of the ligand geometry within the active site, and creation of the CIF is often an error-prone process owing to the great variety of potential ligand chemistry and structure. Stereochemical restraints have been replaced with more robust functionals through the integration of the linear-scaling, semiempirical quantum-mechanics (SE-QM) program DivCon with the PHENIX X-ray refinement engine. The PHENIX/DivCon package has been thoroughly validated on a population of 50 protein–ligand Protein Data Bank (PDB) structures with a range of resolutions and chemistry. The PDB structures used for the validation were originally refined utilizing various refinement packages and were published within the past five years. PHENIX/DivCon does not utilize CIF(s), link restraints and other parameters for refinement and hence it does not make as many a priori assumptions about the model. Across the entire population, the method results in reasonable ligand geometries and low ligand strains, even when the original refinement exhibited difficulties, indicating that PHENIX/DivCon is applicable to both single-structure and high-throughput crystallography.

  12. Communication complexity and information complexity

    Science.gov (United States)

    Pankratov, Denis

    Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

  13. Tandem mass spectrometry: analysis of complex mixtures

    International Nuclear Information System (INIS)

    Singleton, K.E.

    1985-01-01

    Applications of tandem mass spectrometry (MS/MS) for the analysis of complex mixtures results in increased specificity and selectivity by using a variety of reagent gases in both negative and positive ion modes. Natural isotopic abundance ratios were examined in both simple and complex mixtures using parent, daughter and neutral loss scans. MS/MS was also used to discover new compounds. Daughter scans were used to identify seven new alkaloids in a cactus species. Three of these alkaloids were novel compounds, and included the first simple, fully aromatic isoquinoline alkaloids reported in Cactaceae. MS/MS was used to characterize the chemical reaction products of coal in studies designed to probe its macromolecular structure. Negative ion chemical ionization was utilized to study reaction products resulting from the oxidation of coal. Possible structural units in the precursor coal were predicted based on the reaction products identified, aliphatic and aromatic acids and their anhydrides. The MS/MS method was also used to characterize reaction products resulting from coal liquefaction and/or extraction. These studies illustrate the types of problems for which MS/MS is useful. Emphasis has been placed on characterization of complex mixtures by selecting experimental parameters which enhance the information obtained. The value of using MS/MS in conjunction with other analytical techniques as well as the chemical pretreatment is demonstrated

  14. Polyelectrolyte-surfactant complexes formed by poly[3,5-bis(trimethylammoniummethyl)4-hydroxystyrene iodide]-block-poly(ethylene oxide) and sodium dodecyl sulfate in aqueous solutions

    Czech Academy of Sciences Publication Activity Database

    Štěpánek, M.; Matějíček, P.; Procházka, K.; Filippov, Sergey K.; Angelov, Borislav; Šlouf, Miroslav; Mountrichas, G.; Pispas, S.

    2011-01-01

    Roč. 27, č. 9 (2011), s. 5275-5281 ISSN 0743-7463 R&D Projects: GA MŠk ME09059; GA ČR GCP205/11/J043; GA ČR GAP208/10/0353 Institutional research plan: CEZ:AV0Z40500505 Keywords : polyelectrolyte-surfactant complexes * sodium dodecyl sulfate * small-angle X-ray scattering Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.186, year: 2011

  15. Complexity Plots

    KAUST Repository

    Thiyagalingam, Jeyarajan

    2013-06-01

    In this paper, we present a novel visualization technique for assisting the observation and analysis of algorithmic complexity. In comparison with conventional line graphs, this new technique is not sensitive to the units of measurement, allowing multivariate data series of different physical qualities (e.g., time, space and energy) to be juxtaposed together conveniently and consistently. It supports multivariate visualization as well as uncertainty visualization. It enables users to focus on algorithm categorization by complexity classes, while reducing visual impact caused by constants and algorithmic components that are insignificant to complexity analysis. It provides an effective means for observing the algorithmic complexity of programs with a mixture of algorithms and black-box software through visualization. Through two case studies, we demonstrate the effectiveness of complexity plots in complexity analysis in research, education and application. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  16. Toward transferable interatomic van der Waals interactions without electrons: The role of multipole electrostatics and many-body dispersion

    International Nuclear Information System (INIS)

    Bereau, Tristan; Lilienfeld, O. Anatole von

    2014-01-01

    We estimate polarizabilities of atoms in molecules without electron density, using a Voronoi tesselation approach instead of conventional density partitioning schemes. The resulting atomic dispersion coefficients are calculated, as well as many-body dispersion effects on intermolecular potential energies. We also estimate contributions from multipole electrostatics and compare them to dispersion. We assess the performance of the resulting intermolecular interaction model from dispersion and electrostatics for more than 1300 neutral and charged, small organic molecular dimers. Applications to water clusters, the benzene crystal, the anti-cancer drug ellipticine—intercalated between two Watson-Crick DNA base pairs, as well as six macro-molecular host-guest complexes highlight the potential of this method and help to identify points of future improvement. The mean absolute error made by the combination of static electrostatics with many-body dispersion reduces at larger distances, while it plateaus for two-body dispersion, in conflict with the common assumption that the simple 1/R 6 correction will yield proper dissociative tails. Overall, the method achieves an accuracy well within conventional molecular force fields while exhibiting a simple parametrization protocol

  17. Toward transferable interatomic van der Waals interactions without electrons: The role of multipole electrostatics and many-body dispersion

    Energy Technology Data Exchange (ETDEWEB)

    Bereau, Tristan, E-mail: bereau@mpip-mainz.mpg.de [Max-Planck-Institut für Polymerforschung, Ackermannweg 10, 55128 Mainz, Germany and Department of Chemistry, University of Basel, 4056 Basel (Switzerland); Lilienfeld, O. Anatole von [Department of Chemistry, Institute of Physical Chemistry, University of Basel, 4056 Basel, Switzerland and Argonne Leadership Computing Facility, Argonne National Laboratory, Argonne, Illinois 60439 (United States)

    2014-07-21

    We estimate polarizabilities of atoms in molecules without electron density, using a Voronoi tesselation approach instead of conventional density partitioning schemes. The resulting atomic dispersion coefficients are calculated, as well as many-body dispersion effects on intermolecular potential energies. We also estimate contributions from multipole electrostatics and compare them to dispersion. We assess the performance of the resulting intermolecular interaction model from dispersion and electrostatics for more than 1300 neutral and charged, small organic molecular dimers. Applications to water clusters, the benzene crystal, the anti-cancer drug ellipticine—intercalated between two Watson-Crick DNA base pairs, as well as six macro-molecular host-guest complexes highlight the potential of this method and help to identify points of future improvement. The mean absolute error made by the combination of static electrostatics with many-body dispersion reduces at larger distances, while it plateaus for two-body dispersion, in conflict with the common assumption that the simple 1/R{sup 6} correction will yield proper dissociative tails. Overall, the method achieves an accuracy well within conventional molecular force fields while exhibiting a simple parametrization protocol.

  18. Complexity Theory

    Science.gov (United States)

    Lee, William H K.

    2016-01-01

    A complex system consists of many interacting parts, generates new collective behavior through self organization, and adaptively evolves through time. Many theories have been developed to study complex systems, including chaos, fractals, cellular automata, self organization, stochastic processes, turbulence, and genetic algorithms.

  19. A new on-axis micro-spectrophotometer for combining Raman, fluorescence and UV/Vis absorption spectroscopy with macromolecular crystallography at the Swiss Light Source.

    Science.gov (United States)

    Pompidor, Guillaume; Dworkowski, Florian S N; Thominet, Vincent; Schulze-Briese, Clemens; Fuchs, Martin R

    2013-09-01

    The combination of X-ray diffraction experiments with optical methods such as Raman, UV/Vis absorption and fluorescence spectroscopy greatly enhances and complements the specificity of the obtained information. The upgraded version of the in situ on-axis micro-spectrophotometer, MS2, at the macromolecular crystallography beamline X10SA of the Swiss Light Source is presented. The instrument newly supports Raman and resonance Raman spectroscopy, in addition to the previously available UV/Vis absorption and fluorescence modes. With the recent upgrades of the spectral bandwidth, instrument stability, detection efficiency and control software, the application range of the instrument and its ease of operation were greatly improved. Its on-axis geometry with collinear X-ray and optical axes to ensure optimal control of the overlap of sample volumes probed by each technique is still unique amongst comparable facilities worldwide and the instrument has now been in general user operation for over two years.

  20. A new on-axis micro-spectrophotometer for combining Raman, fluorescence and UV/Vis absorption spectroscopy with macromolecular crystallography at the Swiss Light Source

    Science.gov (United States)

    Pompidor, Guillaume; Dworkowski, Florian S. N.; Thominet, Vincent; Schulze-Briese, Clemens; Fuchs, Martin R.

    2013-01-01

    The combination of X-ray diffraction experiments with optical methods such as Raman, UV/Vis absorption and fluorescence spectroscopy greatly enhances and complements the specificity of the obtained information. The upgraded version of the in situ on-axis micro-spectrophotometer, MS2, at the macromolecular crystallography beamline X10SA of the Swiss Light Source is presented. The instrument newly supports Raman and resonance Raman spectroscopy, in addition to the previously available UV/Vis absorption and fluorescence modes. With the recent upgrades of the spectral bandwidth, instrument stability, detection efficiency and control software, the application range of the instrument and its ease of operation were greatly improved. Its on-axis geometry with collinear X-ray and optical axes to ensure optimal control of the overlap of sample volumes probed by each technique is still unique amongst comparable facilities worldwide and the instrument has now been in general user operation for over two years. PMID:23955041