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Sample records for gd-tex-malonato-platinum conjugates synthesis

  1. Conjugated Fatty Acid Synthesis

    Science.gov (United States)

    Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

    2012-01-01

    Conjugated linolenic acids (CLNs), 18:3 Δ9,11,13, lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ9,12,15). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ9cis,11trans,13cis) or α-eleostearic acid (18:3 Δ9cis,11trans,13trans). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation. PMID:22451660

  2. Parallel synthesis and screening of peptide conjugates.

    Science.gov (United States)

    Dirksen, Anouk; Madsen, Mark; Dello Iacono, Giuseppe; Matin, Marla J; Bacica, Michael; Stanković, Nebojša; Callans, Sherri; Bhat, Abhijit

    2014-06-18

    Peptide conjugates represent an emerging class of therapeutics. However, in contrast to that of small molecules and peptides, the discovery and optimization of peptide conjugates is low in throughput, resource intensive, time-consuming, and based on educated decisions rather than screening. A strategy for the parallel synthesis and screening of peptide conjugates is presented that (1) reduces variability in the conjugation steps; (2) provides a new method to rapidly and quantitatively measure conversion in crude conjugation mixtures; (3) introduces a purification step using an immobilized chemical scavenger that does not rely on protein-specific binding; and (4) is supported by robust analytical methods to characterize the large number of end products. Copper-free click chemistry is used as the chemoselective ligation method for conjugation and purification. The productivity in the generation and screening of peptide conjugates is significantly improved by applying this strategy as is demonstrated by the optimization of the anti-Angiopoietin-2 (Ang2) CovX-body, CVX-060, a peptide-antibody scaffold conjugate that has advanced in clinical trials for oncology indications.

  3. Design, synthesis, characterization and study of novel conjugated polymers

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wu [Iowa State Univ., Ames, IA (United States)

    1997-06-24

    After introducing the subject of conjugated polymers, the thesis has three sections each containing a literature survey, results and discussion, conclusions, and experimental methods on the following: synthesis, characterization of electroluminescent polymers containing conjugated aryl, olefinic, thiophene and acetylenic units and their studies for use in light-emitting diodes; synthesis, characterization and study of conjugated polymers containing silole unit in the main chain; and synthesis, characterization and study of silicon-bridged and butadiene-linked polythiophenes.

  4. One-pot synthesis of conjugated trienes

    Czech Academy of Sciences Publication Activity Database

    Šebesta, Petr; Jahn, Ullrich

    2009-01-01

    Roč. 103, č. 11 (2009), s. 990-990 ISSN 0009-2770. [Pokroky v organické, bioorganické a farmaceutické chemii /44./. 27.11.2009-29.11.2009, Liblice] Institutional research plan: CEZ:AV0Z40550506 Keywords : pheromones * Suzuki coupling * conjugated trienes Subject RIV: CC - Organic Chemistry

  5. Rapid, facile synthesis of conjugated polymer zwitterions in ionic liquids

    Energy Technology Data Exchange (ETDEWEB)

    Page, Zachariah A. [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Liu, Feng [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Russell, Thomas P. [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Emrick, Todd [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA

    2014-01-01

    Ionic liquids (ILs) were utilized for the rapid air-stable Suzuki polymerization of polar zwitterionic thiophene monomers, precluding the need for volatile organic solvents, phosphine ligands and phase transfer catalysts typically used in conjugated polymer synthesis.

  6. Synthesis of regioregular pentacene-containing conjugated polymers

    KAUST Repository

    Okamoto, Toshihiro

    2011-01-01

    We report the synthesis and characterization of a new class of regioregular pentacene-containing conjugated polymers via our synthetic routes reported previously. We found that our regioregular pentacene polymers showed improved ordering than their regiorandom counterpart as well as ambipolar OFET performance. © 2011 The Royal Society of Chemistry.

  7. Synthesis of oligogalacturonates conjugated to BSA

    DEFF Research Database (Denmark)

    Clausen, Mads Hartvig; Madsen, Robert

    2004-01-01

    The synthesis of three oligogalacturonates with an aldehyde spacer attached at the reducing end is described. Trigalacturonates a-D-GalpA-(1-4)-a-D-GalpA-(1-4)-a-D-GalpA-(1-O(CH2)7CHO and a-D-GalpA(Me)-(1-4)-a-D-GalpA(Me)-(1-4)-a-D-GalpA(Me)-(1-O(CH2)7CHO as well as hexagalacturonate a-D-GalpA-(1...

  8. Polyphenol-chitosan conjugates: Synthesis, characterization, and applications.

    Science.gov (United States)

    Hu, Qiaobin; Luo, Yangchao

    2016-10-20

    Chitosan, the only positively charged polysaccharide in the world, is very attractive for food, medicinal and pharmaceutical applications because of its promising properties, including non-toxicity, superb biodegradability, high biocompatibility, abundant availability and low cost. In order to overcome the poor water solubility and widen the applications of chitosan, various polyphenol-chitosan conjugates have been synthesized in recent years. The present review focuses on the chitosan-based conjugates formed using different polyphenols, including gallic acid, caffeic acid, ferulic acid, salicylic acid, catechin, and EGGE, etc. Three major synthesis techniques, namely, activated ester-mediated modification, enzyme-mediated strategy, and free radical induced grafting approach are introduced in detail. In addition, the new physicochemical and biological properties of polyphenol-chitosan conjugates are introduced, including water solubility, thermo stability, in vitro and in vivo antioxidant activity, antimicrobial and anticancer activity. Furthermore, the novel applications of each conjugate are discussed in detail. Lastly, the challenges and prospective areas of study related to polyphenol-chitosan are summarized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Synthesis of Regiospecifically Fluorinated Conjugated Dienamides

    Science.gov (United States)

    Chowdhury, Mohammad; Mandal, Samir K.; Banerjee, Shaibal; Zajc, Barbara

    2015-01-01

    Modular synthesis of regiospecifically fluorinated 2,4-diene Weinreb amides, with defined stereochemistry at both double bonds, was achieved via two sequential Julia-Kocienski olefinations. In the first step, a Z-α-fluorovinyl Weinreb amide unit with a benzothiazolylsulfanyl substituent at the allylic position was assembled. This was achieved via condensation of two primary building blocks, namely 2-(benzo[d]thiazol-2-ylsulfonyl)-2-fluoro-N-methoxy-N-methylacetamide (a Julia-Kocienski olefination reagent) and 2-(benzo[d]thiazol-2-ylthio)acetaldehyde (a bifunctional building block). This condensation was highly Z-selective and proceeded in a good 76% yield. Oxidation of benzothiazolylsulfanyl moiety furnished a second-generation Julia-Kocienski olefination reagent, which was used for the introduction of the second olefinic linkage via DBU-mediated condensations with aldehydes, to give (2Z,4E/Z)-dienamides in 50%–74% yield. Although olefinations were 4Z-selective, (2Z,4E/Z)-2-fluoro-2,4-dienamides could be readily isomerized to the corresponding 5-substituted (2Z,4E)-2-fluoro-N-methoxy-N-methylpenta-2,4-dienamides in the presence of catalytic iodine. PMID:24727415

  10. Synthesis of Regiospecifically Fluorinated Conjugated Dienamides

    Directory of Open Access Journals (Sweden)

    Mohammad Chowdhury

    2014-04-01

    Full Text Available Modular synthesis of regiospecifically fluorinated 2,4-diene Weinreb amides, with defined stereochemistry at both double bonds, was achieved via two sequential Julia-Kocienski olefinations. In the first step, a Z-a-fluorovinyl Weinreb amide unit with a benzothiazolylsulfanyl substituent at the allylic position was assembled. This was achieved via condensation of two primary building blocks, namely 2-(benzo[d]thiazol-2-ylsulfonyl-2-fluoro-N-methoxy-N-methylacetamide (a Julia-Kocienski olefination reagent and 2-(benzo[d]thiazol-2-ylthioacetaldehyde (a bifunctional building block. This condensation was highly Z-selective and proceeded in a good 76% yield. Oxidation of benzothiazolylsulfanyl moiety furnished a second-generation Julia-Kocienski olefination reagent, which was used for the introduction of the second olefinic linkage via DBU-mediated condensations with aldehydes, to give (2Z,4E/Z-dienamides in 50%–74% yield. Although olefinations were 4Z-selective, (2Z,4E/Z-2-fluoro-2,4-dienamides could be readily isomerized to the corresponding 5-substituted (2Z,4E-2-fluoro-N-methoxy-N-methylpenta-2,4-dienamides in the presence of catalytic iodine.

  11. Synthesis and study of conjugated polymers containing Di- or Triphenylamine

    Energy Technology Data Exchange (ETDEWEB)

    Sukwattanasinitt, M.

    1996-06-21

    This thesis consists of two separate parts. The first part addresses the synthesis and study of conjugated polymers containing di- or triphenylamine. Two types of polymers: linear polymers and dendrimers, were synthesized. The polymers were characterized by NMR, IR, UV, GPC, TGA and DSC. Electronic and optical properties of the polymers were studied through the conductivity measurements and excitation- emission spectra. the second part of this thesis deals with a reaction of electron-rich acetylenes with TCNE. The discovery of the reaction from charge transfer complex studies and the investigation of this reaction on various electron-rich acetylenes are presented.

  12. Synthesis and characterization of highly conjugated, chiral bridging ligands.

    Science.gov (United States)

    Sauers, Angela L; Ho, Douglas M; Bernhard, Stefan

    2004-12-10

    This paper describes the synthesis of four chiral derivatives of the electronically highly conjugated tetra-2-pyridylpyrazine (TPPZ) bridging ligand, which are denoted (R)- and (S)-4,5- and 5,6-pineno-tetra-2-pyridylpyrazine (PTPPZ). Preparation of these ligands was undertaken through the use of commercially available, enantiomerically pure (1R)- and (1S)-alpha-pinene, which was functionalized and subsequently employed in a Krohnke pyridine synthesis involving a furan-substituted pyridinium salt to yield a chiral, furan-substituted pyridyl intermediate. Oxidative degradation and subsequent reduction of this furan led to a chiral, substituted 2-pyridylaldehyde, which underwent a pyridoin condensation followed by cyclization to produce the final PTPPZ ligands.

  13. Controlled polymerizations for the synthesis of semiconducting conjugated polymers

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, Ken; Luscombe, Christine K.

    2011-01-01

    Conjugated polymers have been under active development since the 1970s as the active material in organic field-effect transistors (OFETs), photovoltaic devices and the emissive layer in light-emitting diodes (LEDs). Extensive work has been performed to investigate the physics and chemistry of these materials, and a variety of semiconducting polymers have been synthesized using a range of polymerization techniques. One of the most important key technologies is to obtain a well-controlled polymerization, which provides polymers with narrow polydispersities and defined molecular weights. In this paper, we describe the recent progress on the synthesis of semiconducting polymers as classified as polyphenylenes, polyphenylenevinylenes, polythiophenes, polyfluorene and their block copolymers by the use of controlled polymerizations.

  14. Carbohydrate protease conjugates: Stabilized proteases for peptide synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Wartchow, C.A.; Wang, Peng; Bednarski, M.D.; Callstrom, M.R. [Ohio State Univ., Columbus, OH (United States)]|[Lawrence Berkeley Lab., CA (United States)

    1995-12-31

    The synthesis of oligopeptides using stable carbohydrate protease conjugates (CPCs) was examined in acetonitrile solvent systems. CPC[{alpha}-chymotrypsin] was used for the preparation of peptides containing histidine, phenylalanine, tryptophan in the P{sub 1} position in 60-93% yield. The CPC[{alpha}-chymotrypsin]-catalyzed synthesis of octamer Z-Gly-Gly-Phe-Gly-Gly-Phe-Gly-Gly-OEt from Z-Gly-Gly-Phe-Gly-Gly-Phe-OMe was achieved in 71% yield demonstrating that synthesis peptides containing both hydrophylic and hydrophobic amino acids. The P{sub 2} specificity of papain for aromatic residues was utilized for the 2 + 3 coupling of Z-Tyr-Gly-OMe to H{sub 2}N-Gly-Phe-Leu-OH to generate the leucine enkephalin derivative in 79% yield. Although papain is nonspecific for the hydrolysis of N-benzyloxycarbonyl amino acid methyl esters in aqueous solution, the rates of synthesis for these derivitives with nucleophile leucine tert-butyl ester differed by nearly 2 orders of magnitude. CPC[thermolysin] was used to prepare the aspartame precursor Z-Asp-Phe-OMe in 90% yield. The increased stability of CPCs prepared from periodate-modified poly(2-methacryl- amido-2-deoxy-D-glucose), poly(2-methacrylamido-2-deoxy-D-galactose), and poly(5-methacryl-amido-5-deoxy-D-ribose), carbohydrate materials designed to increase the aldehyde concentration in aqueous solution, suggests that the stability of CPCs is directly related to the aldehyde concentration of the carbohydrate material. Periodate oxidation of poly(2-methacrylamido-2-deoxy-D-glucose) followed by covalent attachment to {alpha}-chymotrypsin gave a CPC with catalytic activity in potassium phosphate buffer at 90{degrees}C for 2 h. 1 fig., 1 tab., 40 refs.

  15. Seeking Polymeric Prodrugs of Norfloxacin. Part 2. Synthesis and Structural Analysis of Polyurethane Conjugates

    Directory of Open Access Journals (Sweden)

    Waclaw Kolodziejski

    2010-02-01

    Full Text Available Oligo(ε-caprolactone and oligolactide were synthesized via ring-opening polymerization of cyclic esters in the presence of creatinine as initiators. Thus obtained oligomers were successfully used in the synthesis of novel polyurethane conjugates of norfloxacin. The structures of the polymers and conjugates were elucidated by means of MALDI-TOF MS, NMR and IR studies.

  16. Synthesis, characterization and the release kinetics of antiproliferative agents from polyamidoamine conjugates

    CSIR Research Space (South Africa)

    Aderibigbe, BA

    2015-01-01

    Full Text Available of Microencapsulation: Micro and Nano Carriers Synthesis, characterization and the release kinetics of antiproliferative agents from polyamidoamine conjugates B. A. Aderibigbea, E. R. Sadikub, S. S. Rayc, X. Y. Mbiandad, M. C. Fotsingd, J. Jayaramuduc & S. J...

  17. The Synthesis of Substituted Piperazine-cholesterol Conjugates for ...

    African Journals Online (AJOL)

    A small library of cholesterol-piperazine conjugates were synthesized by the reaction of cholesteryl chloroformate with a set of substituted piperazines in dichloromethane at room temperature. The conjugates, all obtained in good to excellent yields, were synthesized to be key components of nucleic acid transfection ...

  18. Synthesis of sugars catalysed by microgel conjugated rabbit muscle ...

    African Journals Online (AJOL)

    Microgel has been prepared and covalently conjugated to rabbit muscle aldolase and employed to catalyse reactions between dihydroxyacetone phosphate, DHAP natural and non-natural acceptors aldehydes in aqueous, aqueous – organic solvents at ambient temperature. The microgel conjugated enzyme was found to ...

  19. Synthesis and antimicrobial activity of gold nanoparticle conjugates with cefotaxime

    Science.gov (United States)

    Titanova, Elena O.; Burygin, Gennady L.

    2016-04-01

    Gold nanoparticles (GNPs) have attracted significant interest as a novel platform for various applications to nanobiotechnology and biomedicine. The conjugates of GNPs with antibiotics and antibodies were also used for selective photothermal killing of protozoa and bacteria. Also the conjugates of some antibiotics with GNPs decreased the number of bacterial growing cells. In this work was made the procedure optimization for conjugation of cefotaxime (a third-generation cephalosporin antibiotic) with GNPs (15 nm) and we examined the antimicrobial properties of this conjugate to bacteria culture of E. coli K-12. Addition of cefotaxime solution to colloidal gold does not change their color and extinction spectrum. For physiologically active concentration of cefotaxime (3 μg/mL), it was shown that the optimum pH for the conjugation was more than 9.5. A partial aggregation of the GNPs in saline medium was observed at pH 6.5-7.5. The optimum concentration of K2CO3 for conjugation cefotaxime with GNPs-15 was 5 mM. The optimum concentration of cefotaxime was at 0.36 μg/mL. We found the inhibition of the growth of E. coli K12 upon application cefotaxime-GNP conjugates.

  20. Synthesis of gold and silver nanoparticle S-ovalbumin protein conjugates by in situ conjugation process

    Science.gov (United States)

    Joshi, Deepti; Soni, R. K.

    2015-05-01

    Pure gold and silver nanoparticle (NP) generation and their conjugation with protein S-ovalbumin using in situ conjugation process have been reported. The in situ conjugation involves nanosecond pulse laser ablation of pure metal target in the protein S-ovalbumin solution. Transmission electron microscopy (TEM) and UV-Visible absorption results show decrease in mean NP size along with narrow particle size distribution on ablation in S-ovalbumin solution as compared to ablation in water for both Au and Ag NPs. Also, the NP size reduction was found to be dependent on the concentration of S-ovalbumin. For AuNPs, spherical NPs of mean size 4 nm with particle size distribution 2-6 nm were obtained at 300 nM S-ovalbumin concentration. Further, it has been observed that the resultant in situ-conjugated colloid gold and silver NP solutions were quite stable even in the presence of NaCl at physiological salt concentration (0.15 M). On post-laser irradiation (532 nm, 15 mJ) for 20 min, 9 nm red shift in surface plasmon resonance peak (SPR), along with increased broadening towards longer wavelength, was observed in the AuNPs-S-ovalbumin sample. Further increase in the time of irradiation showed shift in AuNPs-S-ovalbumin SPR towards lower wavelength. On laser irradiation (532 nm, 15 mJ) for 20 min, no significant change was observed in the line shape of the plasmon absorption band of the AgNPs-S-ovalbumin conjugate. FTIR spectra revealed that S-ovalbumin peptide backbone and secondary structure remain unchanged on laser irradiation during in situ conjugation process. Thus, integrity of S-ovalbumin does not get affected, and no degradation of S-ovalbumin takes place on laser-induced in situ conjugation. Raman results confirm that both Au and Ag NPs interact with S-ovalbumin via thiol-bearing cysteine residues of the disulfide bond.

  1. Synthesis and characterization of covalent diphenylalanine nanotube-folic acid conjugates

    DEFF Research Database (Denmark)

    León, John Jairo Castillo; Rindzevicius, Tomas; Wu, Kaiyu

    2014-01-01

    Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through coupling of amine groups of PNTs and carboxylic groups of FA. The sur......Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through coupling of amine groups of PNTs and carboxylic groups of FA...... performed on a large area silver-capped (diameter of 62 nm) silicon nanopillars with an approximate height of 400 nm and a width of 200 nm. The results showed that the PNT-FA synthesis procedure preserves the molecular structure of FA. The PNT-FA conjugate presented in this study is a promising candidate...

  2. Synthesis and Antimicrobial Activity of Amino Acids Conjugated Diphenylmethylpiperazine Derivatives

    Directory of Open Access Journals (Sweden)

    K. N. Shivakumara

    2009-01-01

    Full Text Available A series of amino acid conjugated diphenylmethylpiperazine derivatives were synthesized by coupling diphenylmethylpiperazine with different Boc-amino acids using EDCI/HOBt as coupling agent and NMM as base. The synthesized compounds were characterized by 1H-NMR and elemental analysis. The Boc-deblocked derivatives were tested for their antimicrobial activity. We are here reporting that Phe and Trp conjugated diphenylmethylpiperazine showed equally good antibacterial activities as that of conventional antimicrobial drugs.

  3. Synthesis of gold and silver nanoparticle S-ovalbumin protein conjugates by in situ conjugation process

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Deepti, E-mail: deeptimishrajoshi@gmail.com; Soni, R. K. [Indian Institute of Technology Delhi, Physics Department (India)

    2015-05-15

    Pure gold and silver nanoparticle (NP) generation and their conjugation with protein S-ovalbumin using in situ conjugation process have been reported. The in situ conjugation involves nanosecond pulse laser ablation of pure metal target in the protein S-ovalbumin solution. Transmission electron microscopy (TEM) and UV–Visible absorption results show decrease in mean NP size along with narrow particle size distribution on ablation in S-ovalbumin solution as compared to ablation in water for both Au and Ag NPs. Also, the NP size reduction was found to be dependent on the concentration of S-ovalbumin. For AuNPs, spherical NPs of mean size 4 nm with particle size distribution 2–6 nm were obtained at 300 nM S-ovalbumin concentration. Further, it has been observed that the resultant in situ-conjugated colloid gold and silver NP solutions were quite stable even in the presence of NaCl at physiological salt concentration (0.15 M). On post-laser irradiation (532 nm, 15 mJ) for 20 min, 9 nm red shift in surface plasmon resonance peak (SPR), along with increased broadening towards longer wavelength, was observed in the AuNPs–S-ovalbumin sample. Further increase in the time of irradiation showed shift in AuNPs–S-ovalbumin SPR towards lower wavelength. On laser irradiation (532 nm, 15 mJ) for 20 min, no significant change was observed in the line shape of the plasmon absorption band of the AgNPs–S-ovalbumin conjugate. FTIR spectra revealed that S-ovalbumin peptide backbone and secondary structure remain unchanged on laser irradiation during in situ conjugation process. Thus, integrity of S-ovalbumin does not get affected, and no degradation of S-ovalbumin takes place on laser-induced in situ conjugation. Raman results confirm that both Au and Ag NPs interact with S-ovalbumin via thiol-bearing cysteine residues of the disulfide bond.

  4. Synthesis and characterization of nido-carborane-cobalamin conjugates

    International Nuclear Information System (INIS)

    Hogenkamp, Harry P.C.; Collins, Douglas A.; Live, David; Benson, Linda M.; Naylor, Stephen

    2000-01-01

    Three vitamin B 12 (cyanocobalamin) conjugates bearing one nido-carborane molecule or two nido-carborane molecules linked to the propionamide side chains via a four carbon linker have been synthesized. Reaction of o-carboranoylchloride with 1,4-diaminobutane in pyridine produced nido-carboranoyl(4-amidobutyl)amine, which was linked to the b- and d-monocarboxylic acids and the b,d-dicarboxylic acid of cyanocobalamin. Mass spectrometry analysis as well as 11 B nuclear magnetic resonance demonstrated that during the reaction of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin-nido-carborane conjugates was assessed by the unsaturated vitamin B 12 binding capacity assay. When compared with 57 Co cyanocobalamin, the biological activity of cyanocobalamin-b-nido-carborane, cyanocobalamin-d-nido-carborane, and cyanocobalamin-b-d-bis-nido-carborane conjugates were 92.93%, 35.75%, and 37.02%, respectively. These findings suggest that the 10 B cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture therapy

  5. Synthesis and characterization of nido-carborane-cobalamin conjugates

    Energy Technology Data Exchange (ETDEWEB)

    Hogenkamp, Harry P.C. E-mail: hogen001@tc.umn.edu; Collins, Douglas A.; Live, David; Benson, Linda M.; Naylor, Stephen

    2000-01-01

    Three vitamin B{sub 12} (cyanocobalamin) conjugates bearing one nido-carborane molecule or two nido-carborane molecules linked to the propionamide side chains via a four carbon linker have been synthesized. Reaction of o-carboranoylchloride with 1,4-diaminobutane in pyridine produced nido-carboranoyl(4-amidobutyl)amine, which was linked to the b- and d-monocarboxylic acids and the b,d-dicarboxylic acid of cyanocobalamin. Mass spectrometry analysis as well as {sup 11}B nuclear magnetic resonance demonstrated that during the reaction of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin-nido-carborane conjugates was assessed by the unsaturated vitamin B{sub 12} binding capacity assay. When compared with {sup 57}Co cyanocobalamin, the biological activity of cyanocobalamin-b-nido-carborane, cyanocobalamin-d-nido-carborane, and cyanocobalamin-b-d-bis-nido-carborane conjugates were 92.93%, 35.75%, and 37.02%, respectively. These findings suggest that the {sup 10}B cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture therapy.

  6. Expeditious synthesis of coumarin-pyridone conjugates molecules ...

    Indian Academy of Sciences (India)

    RAJNI KHAJURIA

    2017-09-06

    Sep 6, 2017 ... important character in amyloid formation in Alzheimer's disease.19. Further, in the design of new pharmaceutical agents, the development of conjugate molecules through the combination of different pharmacophores has resulted in the improvement of biological profiles. Adopting this approach, several ...

  7. Naproxen glycine conjugate-synthesis, pharmaceutical preformulation and pharmacodynamic evaluation.

    Science.gov (United States)

    Mishra, Ashutosh; Agrawal, Shalini; Pathak, Kamla

    2012-02-01

    The project was aimed at synthesizing and characterizing amino acid conjugate of naproxen (categorically stated as Type II A prodrug) that is expected to enhance solubility without affecting permeability and is capable of delivering naproxen (NAP) to colon without significant reversion of prodrug in gastrointestinal conditions. Thus, naproxen-glycine conjugate (NAP-GLY) was prepared by conventional coupling method and the prodrug was characterized by FTIR, FTNMR, FAB mass and elemental analysis. The conjugate was then subjected to selected pharmaceutical preformulation studies like pH-solubility analysis, intrinsic dissolution rate and pH partition studies. These studies established 1.24 folds higher solubility of the (NAP-GLY) over NAP in phosphate buffer pH 7.4 without compromising its partitioning ability. The amino acid conjugate demonstrated superior intrinsic dissolution capabilities (30.9% enhancement) than NAP and in vitro reversion studies suggested its potential of safe transit to colon where the moiety is capable of reverting to 78.52% NAP after 72 hrs of the experiment. In vivo evaluation of NAP-GLY in experimentally induced colitis established its efficacy an anti-inflammatory prodrug moiety (ulcer index = 6.73 with respect to 42.5 for control) that was supported by histological studies. In addition to its ability to control colonic ulcers NAP-GLY demonstrated insignificant (P >0.05) gastric ulcerogenic potential. Conclusively, the conjugate when suitably formulated can be considered as therapeutically efficacious drug delivery system with fewer pharmaceutical limitations. © 2012 Informa Healthcare USA, Inc.

  8. Synthesis and photophysicochemical studies of a water soluble conjugate between folic acid and zinc tetraaminophthalocyanine

    Energy Technology Data Exchange (ETDEWEB)

    Khoza, Phindile; Antunes, Edith [Department of Chemistry, Rhodes University, PO Box 94, Grahamstown (South Africa); Chen, Ji-Yao [State Key Laboratory of Surface Physics and Department of Physics, Fudan University, Shanghai 200433 (China); Nyokong, Tebello, E-mail: t.nyokong@ru.ac.za [Department of Chemistry, Rhodes University, PO Box 94, Grahamstown (South Africa)

    2013-02-15

    This work reports on the synthesis of zinc tetraaminophthalocyanine (ZnTAPc) functionalized with folic acid (FA), forming ZnTAPcFA. The conjugate between FA and ZnTAPc was soluble in water whereas ZnTAPc alone is not. The structure of ZnTAPcFA conjugate was elucidated by {sup 1}H NMR, MALDI-TOF mass and FTIR spectra. Photophysical and photochemical studies of ZnTAPcFA were conducted in DMSO. The increase in fluorescence quantum yield of the conjugate was accompanied by a decrease in the triplet and singlet oxygen quantum yields. The changes in triplet quantum and singlet oxygen quantum yields were marginal when ZnTAPc was simply mixed with FA without a chemical bond. - Highlights: Black-Right-Pointing-Pointer A conjugate between folic acid and a zinc tetraaminophthalocyanine was formed. Black-Right-Pointing-Pointer The conjugate is water soluble even though the phthalocyanine alone is not. Black-Right-Pointing-Pointer The fluorescence quantum yield of the conjugate was enhanced compared to the phthalocyanine alone. Black-Right-Pointing-Pointer Triplet quantum yields decreased for the conjugate.

  9. Synthesis, Characterization, and Saccharide Binding Studies of Bile Acid − Porphyrin Conjugates

    Directory of Open Access Journals (Sweden)

    Vladimír Král

    2007-01-01

    Full Text Available Synthesis and characterization of bile acid-porphyrin conjugates (BAPs are reported. Binding of saccharides with BAPs in aqueous methanol was studied by monitoring changes in the visible absorption spectral of the porphyrin-moieties. Although these studies clearly showed absorbance changes, suggesting quite high if non-selective binding, the mass spectral studies do not unambiguously support these results.

  10. New electroluminescent carbazole-containing conjugated polymer: synthesis, photophysics, and electroluminescence

    Czech Academy of Sciences Publication Activity Database

    Cimrová, Věra; Ulbricht, C.; Dzhabarov, Vagif; Výprachtický, Drahomír; Egbe, D. A. M.

    2014-01-01

    Roč. 55, č. 24 (2014), s. 6220-6226 ISSN 0032-3861 R&D Projects: GA ČR GAP106/12/0827; GA ČR(CZ) GA13-26542S Institutional support: RVO:61389013 Keywords : carbazole-containing conjugated polymer * synthesis * photophysics and electroluminescence Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.562, year: 2014

  11. Synthesis and two-photon absorption property of new -conjugated ...

    Indian Academy of Sciences (India)

    In this communication, we report the synthesis of three newly designed fluorescent polymers P1-P3, starting from simple thiophene derivatives through precursor polyhydrazide route. The new polymers, carrying donor and acceptor heterocyclic moieties with different spacer groups were found to be thermally stable and ...

  12. Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

    Directory of Open Access Journals (Sweden)

    Tatyana V. Abramova

    2013-12-01

    Full Text Available Conjugates of 2’-deoxyguanosine, L-tryptophan and benzophenone designed to study pathways of fast radical reactions by the photo Chemically Induced Dynamic Nuclear Polarization (photo-CIDNP method were obtained by the phosphotriester block liquid phase synthesis. The phosphotriester approach to the oligonucleotide synthesis was shown to be a versatile and economic strategy for preparing the required amount of high quality samples of nucleotide–amino acid conjugates.

  13. Synthesis and cellular uptake of folic acid-conjugated cellulose nanocrystals for cancer targeting.

    Science.gov (United States)

    Dong, Shuping; Cho, Hyung Joon; Lee, Yong Woo; Roman, Maren

    2014-05-12

    Elongated nanoparticles have recently been shown to have distinct advantages over spherical ones in targeted drug delivery applications. In addition to their oblong geometry, their lack of cytotoxicity and numerous surface hydroxyl groups make cellulose nanocrystals (CNCs) promising drug delivery vectors. Herein we report the synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells. Folate receptor-mediated cellular binding/uptake of the conjugate was demonstrated on human (DBTRG-05MG, H4) and rat (C6) brain tumor cells. Folate receptor expression of the cells was verified by immunofluorescence staining. Cellular binding/uptake of the conjugate by DBTRG-05MG, H4, and C6 cells was 1452, 975, and 46 times higher, respectively, than that of nontargeted CNCs. The uptake mechanism was determined by preincubation of the cells with the uptake inhibitors chlorpromazine or genistein. DBTRG-05MG and C6 cells internalized the conjugate primarily via caveolae-mediated endocytosis, whereas H4 cells internalized the conjugate primarily via clathrin-mediated endocytosis.

  14. Quaternary Alkylammonium Conjugates of Steroids: Synthesis, Molecular Structure, and Biological Studies

    Directory of Open Access Journals (Sweden)

    Bogumił Brycki

    2015-11-01

    Full Text Available The methods of synthesis as well as physical, spectroscopic (1H-NMR, 13C-NMR, and FT-IR, ESI-MS, and biological properties of quaternary and dimeric quaternary alkylammonium conjugates of steroids are presented. The results were contrasted with theoretical calculations (PM5 methods and potential pharmacological properties (PASS. Alkylammonium sterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine.

  15. How Chemical Synthesis of Ubiquitin Conjugates Helps To Understand Ubiquitin Signal Transduction.

    Science.gov (United States)

    Hameed, Dharjath S; Sapmaz, Aysegul; Ovaa, Huib

    2017-03-15

    Ubiquitin (Ub) is a small post-translational modifier protein involved in a myriad of biochemical processes including DNA damage repair, proteasomal proteolysis, and cell cycle control. Ubiquitin signaling pathways have not been completely deciphered due to the complex nature of the enzymes involved in ubiquitin conjugation and deconjugation. Hence, probes and assay reagents are important to get a better understanding of this pathway. Recently, improvements have been made in synthesis procedures of Ub derivatives. In this perspective, we explain various research reagents available and how chemical synthesis has made an important contribution to Ub research.

  16. Thermocleavable pi-Conjugated polymers. Synthesis and photovoltaic applications

    Energy Technology Data Exchange (ETDEWEB)

    Helgesen, M.

    2009-10-15

    Polymer solar cells (plastic solar cells) have seen remarkable improvements in recent years where power conversion efficiencies of up to 6% have been reported for small area devices. However in terms of stability polymer solar cells degrade during illumination and in the dark leading to operational lifetimes that are generally very poor. There has been a recent interest in the operational stability of devices and more importantly on the understanding of why devices and materials break down. This has lead to the discovery of a new class of materials that enable exceptionally long device lifetimes (>20000 hours). This Ph.D. thesis describes the synthesis, characterization and photovoltaic applications of these novel polymer materials. A key feature of these materials is that solubilizing thermocleavable alkyl ester side chains are introduced on the polymer backbone. The side chains make the polymer soluble in organic solvents and allow film formation via solution processing. Subsequently they can be removed by heating in a post-processing step forming a harder insoluble material with enhanced stability. These new thermocleavable materials can potentially offer higher chromophore density, higher level processing and improved stability in a solar cell device. Methods are developed for the incorporation of alkoxy chains and thermocleavable ester groups on the benzothiadiazole and the thiophene units in an attempt to evolve the PDTBT system to a more advanced level. The synthesis and photovoltaic applications of the PDTTP and PDTBT systems is described. (author)

  17. Graphene oxide-cationic polymer conjugates: Synthesis and application as gene delivery vectors.

    Science.gov (United States)

    Teimouri, Mohsen; Nia, Azadeh Hashem; Abnous, Khalil; Eshghi, Hossein; Ramezani, Mohammad

    2016-01-01

    Nanomedicine as the interface between nanotechnology and medical sciences is a new area that has attracted the attention of vast groups of researchers. Carbon nanomaterials are common platform for synthesis of nanoparticles for biomedical applications due to their low cytotoxicity and feasible internalization into mammalian cell lines (Yang et al., 2007; Arora et al., 2014; Oh and Park, 2014). Synthesis of vectors based on various cationic polymers polyethylenimine (PEI), polypropylenimine (PPI) and polyamidoamine (PAMAM) and their derivatives were considered as a strategy for transferring plasmid DNA and treatment of genetic diseases. Considering the low cytotoxicity of graphene, chemical modification of its surface has led to fabrication of novel gene delivery systems based on graphene and graphene oxide. Herein we report the synthesis of three groups of vectors based on conjugation of graphene oxide (GO) with alkylated derivatives of three different cationic polymers (polyethylenimine (PEI), polypropylenimine (PPI) and polyamidoamine (PAMAM)) through different linkers including surface carboxyl group, glycine and spermidine. Two main challenges in design of gene delivery vectors is decreasing cytotoxicity while improving the transfection efficiency. All synthesized vectors showed significantly lower cellular toxicity compared to bare polymer. A plasmid encoding green fluorescent protein (GFP) was used to evaluate the transfection efficiency of nanoparticles both qualitatively using live cell fluorescent imaging and quantitatively using flow cytometry and each vector was compared to its polymer base. Most successful conjugation strategy was observed in the case of PEI conjugates among which most efficient vector was PEI-GO conjugate bearing glycine linker. This vector was 9 fold more effective in terms of the percent of EGFP transfected cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

    Directory of Open Access Journals (Sweden)

    Laura Morelli

    2014-10-01

    Full Text Available A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS fragments conjugated to CRM197 as carrier protein have been confirmed at preclinical stage as promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed. We report herein the chemical conjugation of fully synthetic MenX CPS oligomers (monomer, dimer, and trimer to CRM197. Moreover, improvements in some crucial steps leading to the synthesis of MenX CPS fragments are described. Following immunization with the obtained neoglycoconjugates, the conjugated trimer was demonstrated as the minimal fragment possessing immunogenic activity, even though significantly lower than a pentadecamer obtained from the native polymer and conjugated to the same protein. This finding suggests that oligomers longer than three repeating units are possibly needed to mimic the activity of the native polysaccharide.

  19. Synthesis and Exciton Dynamics of Triplet Sensitized Conjugated Polymers

    KAUST Repository

    Andernach, Rolf

    2015-07-22

    We report the synthesis of a novel polythiophene-based host-guest copolymer incorporating a Pt-porphyrin complex (TTP-Pt) into the backbone for efficient singlet to triplet polymer exciton sensitization. We elucidated the exciton dynamics in thin films of the material by means of Transient Absorption Spectrosopcy (TAS) on multiple timescales and investigated the mechanism of triplet exciton formation. During sensitization, single exciton diffusion is followed by exciton transfer from the polymer backbone to the complex where it undergoes intersystem crossing to the triplet state of the complex. We directly monitored the triplet exciton back transfer from the Pt-porphyrin to the polymer and find that 60% of the complex triplet excitons are transferred with a time constant of 1087 ps. We propose an equilibrium between polymer and porphyrin triplet states as a result of the low triplet diffusion length in the polymer backbone and hence an increased local triplet population resulting in increased triplet-triplet annihilation. This novel system has significant implications for the design of novel materials for triplet sensitized solar cells and up-conversion layers.

  20. Research algorithm for synthesis of double conjugation optical systems in the Gauss region

    Directory of Open Access Journals (Sweden)

    A. B. Ostrun

    2014-01-01

    Full Text Available The article focuses on the research of variable magnification optical systems of sophistic class - so-called double conjugation systems. When the magnification changes, they provide two pairs of fixed conjugate planes, namely object and image, as well as entrance and exit pupils. Similar systems are used in microscopy and complex schemes, where it is necessary to conform the pupils of contiguous removable optical components. Synthesis of double conjugation systems in Gauss region is not an easy task. To ensure complete immobility of the exit pupil in the system there should be three movable components or components with variable optical power.Analysis of the literature shows that the design of double conjugation optical system in the paraxial region has been neglected, all methods are not completely universal and suitable for automation.Based on the foregoing, the research and development of a universal method for automated synthesis of double conjugation systems in Gauss region formulated as an objective of the present work seem to be a challenge.To achieve this goal a universal algorithm is used. It is based on the fact that the output coordinates of paraxial rays are multilinear functions of optical surfaces and of axial thicknesses between surfaces. It allows us to create and solve a system of multilinear equations in semi-automatic mode to achieve the chosen values of paraxial characteristics.As a basic scheme for the synthesis a five-component system has been chosen with extreme fixed components and three mobile "internal" ones. The system was considered in two extreme states of moving parts. Initial values of axial thicknesses were taken from Hopkins' patent. Optical force five components were considered unknown. For calculation the system of five equations was created, which allowed us to obtain a certain back focal length, to provide the specified focal length and a fixed position of the exit pupil at a fixed entrance pupil.The scheme

  1. CdS nanowires formed by chemical synthesis using conjugated single-stranded DNA molecules

    Science.gov (United States)

    Sarangi, S. N.; Sahu, S. N.; Nozaki, S.

    2018-03-01

    CdS nanowires were successfully grown by chemical synthesis using two conjugated single-stranded (ss) DNA molecules, poly G (30) and poly C (30), as templates. During the early stage of the synthesis with the DNA molecules, the Cd 2+ interacts with Poly G and Poly C and produces the (Cd 2+)-Poly GC complex. As the growth proceeds, it results in nanowires. The structural analysis by grazing angle x-ray diffraction and transmission electron microscopy confirmed the zinc-blende CdS nanowires with the growth direction of . Although the nanowires are well surface-passivated with the DNA molecules, the photoluminescence quenching was caused by the electron transfer from the nanowires to the DNA molecules. The quenching can be used to detect and label the DNAs.

  2. Synthesis of tocopheryl succinate phospholipid conjugates and monitoring of phospholipase A2 activity

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Viart, Helene Marie-France; Melander, Fredrik

    2012-01-01

    Tocopheryl succinates (TOSs) are, in contrast to tocopherols, highly cytotoxic against many cancer cells. In this study the enzyme activity of secretory phospholipase A2 towards various succinate-phospholipid conjugates has been investigated. The synthesis of six novel phospholipids is described,...

  3. A facile and green ultrasonic-assisted synthesis of BSA conjugated silver nanoparticles.

    Science.gov (United States)

    Gautam, Saurabh; Dubey, Priyanka; Gupta, Munishwar N

    2013-02-01

    The formation and growth of hybrid nanoparticles of a protein BSA and silver by ultrasonic assistance were tracked by surface plasmon resonance signal of silver nanoparticles and light scattering. The hybrid nanoparticles were characterized by surface plasmon resonance spectra, light scattering, TEM, circular dichroism spectroscopy and zeta potential. Size along with the spherical shape of the nanoparticles could be controlled and nanoparticles with diameters ranging from 8 to 140 nm could be obtained, depending upon the ultrasonication time (15-30 min) and molar ratio of AgNO(3)/BSA (20-200). The role of single free thiol group in the reduction of silver ions was also investigated by using DTNB modified BSA and protein conjugated silver nanoparticles were formed even with thiol modified BSA. The growth and size of the nanoparticles were governed by ultrasonic assisted Ostwald ripening. BSA conjugated with silver nanoparticles showed changes in the secondary structure with an increase in the beta sheet structure to 33% as compared to 7% in native BSA as determined by CD spectra. Zeta potential measurements in the pH range of 2.0-12.0 demonstrated that the surface charges of the BSA conjugated silver nanoparticles were similar to that of native BSA suggesting that surface charges and overall three dimensional structure of BSA did not change much. This approach provides a strategy for completely green synthesis of hybrid nanoparticles consisting of a biological entity and an inorganic material. This is the first application of ultrasonic assistance in formation of such hybrid nanomaterials in aqueous media. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Use of carbonyl group addition--elimination reactions for synthesis of nucleic acid conjugates.

    Science.gov (United States)

    Zatsepin, Timofei S; Stetsenko, Dmitry A; Gait, Michael J; Oretskaya, Tatiana S

    2005-01-01

    This review outlines the synthesis of covalent conjugates of oligonucleotides and their analogues that are obtained by reactions of carbonyl compounds with various nucleophiles such as primary amines, N-alkoxyamines, hydrazines, and hydrazides. The products linked by imino, oxime, hydrazone, or thiazolidine groups are shown to be useful intermediates for a wide range of chemical biology applications. Methods for their preparation, isolation, purification, and analysis are highlighted, and the comparative stabilities of the respective linkages are evaluated. The relative merits of incorporation of a carbonyl group, particularly an aldehyde group, into either the oligonucleotide or the ligand parts are considered. Examples of harnessing of aldehyde-nucleophile coupling for the labeling of nucleic acids are given, as well as their conjugation to various biomolecules (e.g. peptides and small molecule ligands), site-specific cross-linking of oligonucleotides to nucleic acid-binding proteins, assembly of multibranched supramolecular structures, and immobilization on functionalized surfaces. Future perspectives of bioconjugation and complex molecular engineering via carbonyl group addition-elimination reactions in nucleic acids chemistry are discussed.

  5. Facile synthesis of bovine serum albumin conjugated low-dimensional ZnS nanocrystals.

    Science.gov (United States)

    Mullamuri, Bhanu; Bhagavathula, Subrahmanya Diwakar; Kasturi, Krishna C S B; Reddy, Venu

    2017-08-01

    We present a facile synthesis of bovine serum albumin (BSA) conjugated low-dimensional ZnS nanocrystals. The experimental parameters such as effects of BSA concentration and precursor vol ratios of Zn:S on the formation of ZnS nanoparticles in BSA matrix were investigated. The ZnS crystalline sizes of 1.9, 1.8 and 1.6nm were obtained by using the BSA concentrations of 1×10 -4 , 5×10 -4 and 10×10 -4 g/mL, respectively, with a fixed Zn:S vol ratio of 1:1. The ZnS samples prepared from 1:10 and 10:1 vol ratios of Zn:S at BSA concentration of 5×10 -4 g/mL shows the crystalline sizes of ZnS are 2.1 and 1.5nm, respectively. FT-IR analysis suggests that the prepared ZnS nanoparticles might be conjugated through the interactions of hydroxyl and amine groups present in BSA. We evaluate the cytotoxicity of the prepared ZnS nanoparticles, the THP-1 cells showed a good viability (>88%) for all the prepared ZnS samples. The plausible mechanism for the formation of ZnS-BSA composite has also been discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Thiophene fused azacoronenes: regioselective synthesis, self organization, charge transport, and its incorporation in conjugated polymers

    Science.gov (United States)

    Liu, Yi; He, Bo

    2015-09-15

    A regioselective synthesis of an azacoronene fused with two peripheral thiophene groups has been realized through a concise synthetic route. The resulting thienoazacoronene (TAC) derivatives show high degree of self-organization in solution, in single crystals, in the bulk, and in spuncast thin films. Spuncast thin film field-effect transistors of the TACs exhibited mobilities up to 0.028 cm.sup.2V.sup.-1 S.sup.-1, which is among the top field effect mobilities for solution processed discotic materials. Organic photovoltaic devices using TAC-containing conjugated polymers as the donor material exhibited a high open-circuit voltage of 0.89 V, which was ascribable to TAC's low-lying highest occupied molecular orbital energy level.

  7. Synthesis of taurine–fluorescein conjugate and evaluation of its retina-targeted efficiency in vitro

    Directory of Open Access Journals (Sweden)

    Meihong Huang

    2014-12-01

    Full Text Available In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F–Tau conjugate. Nuclear magnetic resonance (NMR and high resolution mass spectrometry (HRMS were used to confirm the successful synthesis of F–Tau. The cellular uptake of F–Tau in adult retinal pigment epithelial cells (ARPE-19 and human retinal microvascular endothelial cells (hRMECs was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of logP of F–Tau compared with fluorescein. As compared with fluorescein, F–Tau showed little toxicity, and was retained longer by cells in uptake experiments. F–Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells (P<0.05. These results showed that taurine may be a useful ligand for targeting small-molecule hydrophobic pharmaceuticals into the retina.

  8. Enhancement of antibacterial properties of silver nanoparticles-ceftriaxone conjugate through Mukia maderaspatana leaf extract mediated synthesis.

    Science.gov (United States)

    Harshiny, Muthukumar; Matheswaran, Manickam; Arthanareeswaran, Gangasalam; Kumaran, Shanmugam; Rajasree, Shanmuganathan

    2015-11-01

    Green synthesis of nanoparticles with low range of toxicity and conjugation to antibiotics has become an attractive area of research for several biomedical applications. Nanoconjugates exhibited notable increase in biological activity compared to free antibiotic molecules. With this perception, we report the biosynthesis of silver nanoparticles using aqueous extract of leaves of Mukia maderaspatana and subsequent conjugation of the silver nanoparticles to antibiotic ceftriaxone. The leaves of this plant are known to be a rich source of phenolic compounds with high antioxidant activity that are used as reducing agents. The size, morphology, crystallinity, composition of the synthesized silver nanoparticles and conjugation of ceftriaxone to silver nanoparticles were studied using analytical techniques. The activity of the conjugates against Bacillus subtilis (MTCC 1790), Klebsiella pneumoniae (MTCC 3384), Staphylococcus aureus (ATCC 25923), and Salmonella typhi (MTCC 3224) was compared to ceftriaxone and unconjugated nanoparticles using disc diffusion method. The effect of silver nanoparticles on the reduction of biofilms of Pseudomonas fluorescens (MTCC 6732) was determined by micro plate assay method. The antioxidant activities of extract, silver nitrate, silver nanoparticles, ceftriaxone and conjugates of nanoparticles were evaluated by radical scavenging 1, 1- diphenyl-2-picrylhydrazyl test. Ultraviolet visible spectroscopy and Fourier transform infrared spectroscopy confirmed the formation of metallic silver nanoparticles and conjugation to ceftriaxone. Atomic force microscopy, transmission electron microscopy and particle size analysis showed that the formed particles were of spherical morphology with appreciable nanosize and the conjugation was confirmed by slight increase in surface roughness. The results thus showed that the conjugation of ceftriaxone with silver nanoparticles has better antioxidant and antimicrobial effects than ceftriaxone and unconjugated

  9. Metal-Free, Multicomponent Synthesis of Pyrrole-Based π-Conjugated Polymers from Imines, Acid Chlorides, and Alkynes.

    Science.gov (United States)

    Kayser, Laure V; Vollmer, Moritz; Welnhofer, Merve; Krikcziokat, Hanna; Meerholz, Klaus; Arndtsen, Bruce A

    2016-08-24

    Multicomponent coupling reactions (MCRs) are becoming increasingly used in the synthesis of macromolecules, as they can allow the rapid generation of libraries of materials as a method to tune properties. MCRs could prove particularly useful in the synthesis of π-conjugated polymers in which structural changes are necessary for fine-tuning of electronic properties. We describe here the first metal-free multicomponent approach to conjugated polymers. This reaction exploits the coupling of imines, acid chlorides, and (catechyl)PPh to generate phospha-münchnone-containing polymers, which can be converted to poly(pyrroles) via cycloaddition. The platform allows for the efficient synthesis of families of high molecular weight polymers in one step from readily available monomers.

  10. Enzymatic synthesis of tRNA-peptide conjugates and spectroscopic studies of fluorine-modified RNA

    International Nuclear Information System (INIS)

    Graber, D.

    2010-01-01

    The research presented in this thesis concerns the enzymatic synthesis of artificially modified tRNA, in particular the preparation of non-hydrolysable tRNA-peptide conjugates. Another focus is on NMR-spectroscopic investigations of fluorine-modified RNA. In both projects, chemical methods were developed to address specific RNA-biological research questions. In the first part of this thesis the preparation of tRNA-peptide conjugates with a non-hydrolysable 3'-amide linkage is presented. These molecules are of high relevance for the characterization of ribosomal processes that occur in the peptidyl transferase center (such as peptide bond formation, peptide release, or translocation) using X-ray crystallography and biochemical methods. First, a novel concept to prepare chemically modified ('labeled') tRNA was elaborated based on the combination of solid-phase synthesis and enzymatic ligation. Thereby, a variety of differently labeled tRNAs was achieved. Moreover, the most successful high-yield ligation sites were identified to be situated within the TΨ C-loop. Optimization of the synthesis and the corresponding HPLC-purification of the conjugates were initially conducted with puromycin derivatized tRNA. In the course of this project, also two tRNAs with a ribose 3'-amino group at the terminal adenosine A76 were synthesized. For that purpose a protection group pattern had to be developed to obtain a functionalized solid-support bound to 3'-amino-3'-deoxyadenosine which was appropriate for RNA solid-phase synthesis. The successful preparation of tRNA-peptide conjugates was accomplished in cooperation with Holger Moroder and Jessica Steger (Micura group) who contributed short synthetic RNA-peptide conjugates. These fragments represented the tRNA 3'-termini that were required for exploring the new ligation strategies for non-hydrolisable tRNA - a main aim of this thesis. If the 5'-fragments are synthesized by solid-phase synthesis or in vitro transcription they do not

  11. Synthesis of diethylenetriaminepentaacetic acid conjugated inulin and utility for cellular uptake of liposomes

    International Nuclear Information System (INIS)

    Essien, H.; Lai, J.Y.; Hwang, K.J.

    1988-01-01

    The synthesis, binding of radioactive cations, liposomal encapsulation, and biodistribution of the oxidized-inulin reaction product with ethylenediamine and diethylenetriaminepentaacetic acid (4) are described. The four-step synthesis of the inulin derivative proceeded in a good overall yield of 72%. The complex of the inulin derivative with either 67 Ga3+ or 111 In3+ was stable in vivo and did not readily distribute into tissues, being excreted primarily in urine after intravenous administration to mice. The liposome-entrapped inulin derivative can be loaded with radioactive heavy metal cations by mobile ionophores in high radiochemical yields of 80-91%. Following the intravenous administration of the liposomal encapsulation of the indium-111-labeled inulin derivative, the entrapped compound had a biodistribution characteristic of liposomes and allowed an estimation of the extent of the intracellular uptake of liposomes. The ability of the inulin derivative to chelate many different types of metals will allow the use of this probe for studying subtle differences in tissue distribution resulting from different drug targeting or delivery protocols in the same animal by multiple labeling techniques. Moreover, the chelate-conjugated inulin permits studies of the applications of drug delivery systems in primates or human subjects by noninvasive techniques such as gamma-scintigraphic or nuclear magnetic resonance imaging methods

  12. New heparin–indomethacin conjugate with an ester linkage: Synthesis, self aggregation and drug delivery behavior

    Energy Technology Data Exchange (ETDEWEB)

    Li, Nan-Nan; Zheng, Bing-Na [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Lin, Jian-Tao [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Medical College, Dongguan 523808 (China); Zhang, Li-Ming, E-mail: ceszhlm@mail.sysu.edu.cn [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China)

    2014-01-01

    New heparin–indomethacin conjugate with an ester linkage was prepared by the carbodiimide-mediated condensation reaction, and then characterized by FTIR and {sup 1}HNMR analyses. Due to its amphiphilic character, such a conjugate could self-aggregate into spherical nanoparticles in aqueous system, as confirmed by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. By the in vitro drug release tests, the resultant conjugate nanoparticles were found to have a sustained and esterase-sensitive release behavior for conjugated indomethacin. In addition, the uptake of these conjugate nanoparticles into human nasopharyngeal carcinoma CNE1 cells was confirmed by fluorescence microscopy. - Highlights: • New heparin–indomethacin conjugate with an ester linkage was prepared. • Such a conjugate could self-aggregate into spherical nanoparticles in aqueous system. • The resultant conjugate nanoparticles exhibited an esterase-sensitive drug release behavior. • The resultant conjugate nanoparticles showed the cellular uptake ability in CNE1 cells.

  13. Synthesis, characterization and in vitro cytotoxicity evaluation of polyamidoamine conjugate containing pamidronate and platinum drug

    CSIR Research Space (South Africa)

    Ndamase, AS

    2018-02-01

    Full Text Available Bisphosphonates have been found to be effective when combined with anticancer drugs for chemotherapy. In this paper, pamidronate and platinum complexes were conjugated to linear poly(amidoamine)s (PAMAM) to improve the drug efficacy. The conjugates...

  14. Acyclic Diene Metathesis (ADMET Polymerization for Precise Synthesis of Defect-Free Conjugated Polymers with Well-Defined Chain Ends

    Directory of Open Access Journals (Sweden)

    Tahmina Haque

    2015-03-01

    Full Text Available This accounts introduces unique characteristics by adopting the acyclic diene metathesis (ADMET polymerization for synthesis of conjugated polymers, poly(arylene vinylenes, known as promising molecular electronics. The method is more suitable than the other methods in terms of atom efficiency affording defect-free, stereo-regular (exclusive trans polymers with well-defined chain ends; the resultant polymers possess better property than those prepared by the conventional methods. The chain ends (vinyl group in the resultant polymer prepared by ruthenium-carbene catalyst(s can be modified by treating with molybdenum-alkylidene complex (olefin metathesis followed by addition of various aldehyde (Wittig type cleavage, affording the end-functionalized polymers exclusively. An introduction of initiating fragment, the other conjugated segment, and one-pot synthesis of end-functionalized block copolymers, star shape polymers can be achieved by adopting this methodology.

  15. Methodologies for Controlled Conjugated Polymer Synthesis and Characterization of Small Molecule Organic Semiconductors

    Science.gov (United States)

    Bakus, Ronald C., II

    Conjugated polymers can broadly be described as materials which have a structure composed of repeating monomeric units that show extended electronic communication along the backbone. The extended pi-conjugated nature of these materials gives them a set of unique electronic and optical properties, and has lead to their application in a multitude of various technologies. Of specific interest is the application of these materials in various organic electronics applications, such as solution processed plastic solar cells, light emitting diodes, and field effect transistors. Herein is described the synthesis of a class of well-defined, highly active organometallic initiators for use in controlled polymer synthesis. The polymers prepared using the nickel based initiators in Grignard metathesis polymerization posses the following characteristics: rapid generation of high molecular weight polymers, low polydispersity, linear relation between monomer conversion and molecular weight growth, and the selective transfer of an initiating moiety from the organometallic initiator to one polymer chain end. This initiator was then used to prepare a new class of biosensor materials wherein the polymer had a well defined biosensing end group. Additionally, a series of small molecule donors have been developed that have shown promise in a wide variety of organic electronic applications. These materials can broadly be described as having a D'ADAD' type structure where D, D', and A correspond to electron rich and electron deficient aromatic heterocycles, respectively. By tuning the identity of these groups and the side-chains attached to them, one can subtly influence the optical, electronic, and physical properties of the materials. These materials were investigated via single crystal x-ray diffraction studies to gain insight into how changes to the molecule structure such as heteroatom regioisomerism and isoelectronic substitutions effected the molecular structure. These changes in

  16. Covalently bound conjugates of albumin and heparin: Synthesis, fractionation and characterization

    NARCIS (Netherlands)

    Hennink, Wim E.; Feijen, Jan; Ebert, Charles D.; Kim, Sung Wan

    1983-01-01

    Covalently bound conjugates of human serum albumin and heparin were prepared as compounds which could improve the blood-compatibility of polymer surfaces either by preadsorption or by covalent coupling of the conjugates onto blood contacting surfaces. The conjugates (10–16 weight % of heparin) were

  17. Chemo-Enzymatic Synthesis of Ester-Linked 2-Phenylindole-3-Carboxaldehyde-Monosaccharide Conjugate as Potential Prodrug

    Directory of Open Access Journals (Sweden)

    Kei Shimoda

    2012-01-01

    Full Text Available Chemo-enzymatic synthesis of ester-linked 2-phenylindole-3-carboxaldehyde-glucose conjugate (2-phenylindole-3-carboxyl-10″-O-β-D-glucosyl ester was achieved by using plant cell cultures as biocatalysts. The anticancer agent, 2-phenylindole-3-carboxaldehyde, induced apoptosis in cells, whereas 2-phenylindole-3-carboxyl-10″-O-β-D-glucosyl ester showed no cytotoxicity and induced no apoptosis.

  18. Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake

    International Nuclear Information System (INIS)

    Parab, Harshala J; Huang, Jing-Hong; Liu, Ru-Shi; Lai, Tsung-Ching; Jan, Yi-Hua; Wang, Jui-Ling; Hsiao, Michael; Chen, Chung-Hsuan; Hwu, Yeu-Kuang; Tsai, Din Ping; Chuang, Shih-Yi; Pang, Jong-Hwei S

    2011-01-01

    The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface modification of Au-HMP nanoparticles was carried out using polyethylene glycol and transferrin to produce molecular probes for possible clinical applications. In vitro cell viability studies performed using as-synthesized Au-HMP nanoparticles and their surface-modified counterparts reveal the biocompatibility of the nanoparticles. The transferrin-conjugated nanoparticles have significantly higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral mucosa fibroblast cells), as determined by inductively coupled plasma mass spectrometry. This study demonstrates the possibility of using an inexpensive and non-toxic food additive, HMP, as a stabilizer in the large-scale generation of biocompatible and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

  19. Emitting oligomer containing quinoline group: Synthesis and photophysical properties of conjugated oligomer obtained by Wittig reaction

    Energy Technology Data Exchange (ETDEWEB)

    Karpagam, S., E-mail: skarpagam80@yahoo.com [Organic Chemistry Division, School of Advanced Science, VIT University, Vellore 14, Tamil Nadu (India); Guhanathan, S. [Department of Chemistry, Muthurangam Government Arts College, Vellore, Tamil Nadu (India)

    2014-01-15

    Dichloro quinoline substituted phenylene vinylene oligomer (QUI-OPV) was synthesized via Wittig route. Formation of the oligomer was characterized by spectral (FTIR, {sup 1}H and {sup 13}C NMR), elemental and gel permeation chromatography analysis. The oligomer possesses excellent thermal stability (decomposition temperature 470 °C), solubility in common organic solvents and high glass transition temperature (61 °C). The morphology of the oligomer film of one dimensional (1D) and three dimensional (3D) architectures was observed using atomic force microscopy (AFM). In CHCl{sub 3} solution, the oligomer showed the absorption maxima at 382 nm and also observed excellent photoluminescence (PL) with bluish green emission maxima at shorter wavelengths of 477 nm. The introduction of quinoline to the main chain resulted in a slight decrease of effective conjugation length and exhibited the blue shift in both the absorption and emission spectra. -- Highlights: • Simple synthesis of quinoline functionalized phenylene vinylene oligomer by Wittig route. • The materials had good organosolubility and intrinsic viscosity. • High thermal stability and good surface roughness morphology were observed. • Performance of luminescence improved via introducing quinoline into PPV. • Electrochemical and optical band gap of the oligomer were consistent with each other.

  20. Synthesis of retinoid vitamin A-vitamin B6 conjugate analogues for antiviral chemotherapy

    International Nuclear Information System (INIS)

    Kesel, Andreas J.

    2003-01-01

    The synthesis of retinoid vitamin A-vitamin B 6 conjugate analogues from a vitamin B 6 coenzyme analogue and putative HIV-1 trans-activating transcriptional regulatory protein Tat antagonist (Z)-5 ' -O-phosphono-pyridoxylidenerhodanine (B6PR) monosodium salt hemiheptadecahydrate [(Z)-B6PRNa8.5H 2 O] is discussed here. All-trans-retinoic acid (ATRA) is coupled to B6PR by a modified Stork enamine acylation. It results in a product library of more than eight compounds, each with at least one intact all-trans or 13-cis vitamin A double bond system. This yellow oily concentrate mixture was subjected to matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry (MS), UV/VIS-spectrophotometry, and proton nuclear magnetic resonance spectroscopy ( 1 H-NMR). The chemical structures of six components of the concentrate mixture could be established by combination of these analytical methods. The two main components are 65% 2 ' C,3O-(all-trans-retinylidyne)B6PT (B6RA) and 25% 2 ' C-(all-trans-retinoyl)B6PT, chemically derived from (5RS)-5-(5 ' -O-phosphono-pyridoxyl)-2,4-thiazolidinedione (B6PT). This new retinoid selection could be of further interest in antiviral applications, especially treating conditions caused by RNA viruses like HIV

  1. Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake

    Energy Technology Data Exchange (ETDEWEB)

    Parab, Harshala J; Huang, Jing-Hong; Liu, Ru-Shi [Department of Chemistry, National Taiwan University, Taipei 106, Taiwan (China); Lai, Tsung-Ching; Jan, Yi-Hua; Wang, Jui-Ling; Hsiao, Michael; Chen, Chung-Hsuan [Genomics Research Center, Academia Sinica, Taipei 115, Taiwan (China); Hwu, Yeu-Kuang [Institute of Physics, Academia Sinica, Taipei 115, Taiwan (China); Tsai, Din Ping [Department of Physics, National Taiwan University, Taipei 106, Taiwan (China); Chuang, Shih-Yi; Pang, Jong-Hwei S, E-mail: rsliu@ntu.edu.tw, E-mail: mhsiao@gate.sinica.edu.tw [Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan (China)

    2011-09-30

    The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface modification of Au-HMP nanoparticles was carried out using polyethylene glycol and transferrin to produce molecular probes for possible clinical applications. In vitro cell viability studies performed using as-synthesized Au-HMP nanoparticles and their surface-modified counterparts reveal the biocompatibility of the nanoparticles. The transferrin-conjugated nanoparticles have significantly higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral mucosa fibroblast cells), as determined by inductively coupled plasma mass spectrometry. This study demonstrates the possibility of using an inexpensive and non-toxic food additive, HMP, as a stabilizer in the large-scale generation of biocompatible and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

  2. Folate/NIR 797-conjugated albumin magnetic nanospheres: synthesis, characterisation, and in vitro and in vivo targeting evaluation.

    Science.gov (United States)

    Tang, Qiusha; An, Yanli; Liu, Dongfang; Liu, Peidang; Zhang, Dongsheng

    2014-01-01

    A practical and effective strategy for synthesis of Folate-NIR 797-conjugated Magnetic Albumin Nanospheres (FA-NIR 797-MAN) was developed. For this strategy, Magnetic Albumin Nanospheres (MAN), composed of superparamagnetic iron oxide nanoparticles (SPIONs) and bovine serum albumin (BSA), were covalently conjugated with folic acid (FA) ligands to enhance the targeting capability of the particles to folate receptor (FR) over-expressing tumours. Subsequently, a near-infrared (NIR) fluorescent dye NIR 797 was conjugated with FA-conjugated MAN for in vivo fluorescence imaging. The FA-NIR 797-MAN exhibited low toxicity to a human nasopharyngeal epidermal carcinoma cell line (KB cells). Additionally, in vitro and in vivo evaluation of the dynamic behaviour and targeting ability of FA-NIR 797-MAN to KB tumours validated the highly selective affinity of FA-NIR 797-MAN for FR-positive tumours. In summary, the FA-NIR 797-MAN prepared here exhibited great potential for tumour imaging, since the near-infrared fluorescence contrast agents target cells via FR-mediated endocytosis. The high fluorescence intensity together with the targeting effect makes FA-NIR 797-MAN a promising candidate for imaging, monitoring, and early diagnosis of cancer at the molecular and cellular levels.

  3. Folate/NIR 797-conjugated albumin magnetic nanospheres: synthesis, characterisation, and in vitro and in vivo targeting evaluation.

    Directory of Open Access Journals (Sweden)

    Qiusha Tang

    Full Text Available A practical and effective strategy for synthesis of Folate-NIR 797-conjugated Magnetic Albumin Nanospheres (FA-NIR 797-MAN was developed. For this strategy, Magnetic Albumin Nanospheres (MAN, composed of superparamagnetic iron oxide nanoparticles (SPIONs and bovine serum albumin (BSA, were covalently conjugated with folic acid (FA ligands to enhance the targeting capability of the particles to folate receptor (FR over-expressing tumours. Subsequently, a near-infrared (NIR fluorescent dye NIR 797 was conjugated with FA-conjugated MAN for in vivo fluorescence imaging. The FA-NIR 797-MAN exhibited low toxicity to a human nasopharyngeal epidermal carcinoma cell line (KB cells. Additionally, in vitro and in vivo evaluation of the dynamic behaviour and targeting ability of FA-NIR 797-MAN to KB tumours validated the highly selective affinity of FA-NIR 797-MAN for FR-positive tumours. In summary, the FA-NIR 797-MAN prepared here exhibited great potential for tumour imaging, since the near-infrared fluorescence contrast agents target cells via FR-mediated endocytosis. The high fluorescence intensity together with the targeting effect makes FA-NIR 797-MAN a promising candidate for imaging, monitoring, and early diagnosis of cancer at the molecular and cellular levels.

  4. Synthesis of poly(ethylene glycol)-silk fibroin conjugates and surface interaction between L-929 cells and the conjugates.

    Science.gov (United States)

    Gotoh, Y; Tsukada, M; Minoura, N; Imai, Y

    1997-02-01

    Poly(ethylene glycol) (PEG)-silk fibroin (SF) conjugates (PEG2-SF) were prepared by the chemical modification of solubilized SF with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine (actPEG2) in borate buffer at 37 degrees C. The IR spectra and DSC curves of PEG2-SF and SF suggested the introduction of PEG into SF by the modification and the beta-sheet structure of both SF and PEG2-SF induced by the treatment with methanol aqueous solutions. The content of the PEG component in PEG2-SF was evaluated to be 67% by weight from the melting enthalpy change of PEG observed on the DSC thermogram of PEG2-SF. Water content and contact angle measurements of SF before and after the modification indicated that the hydrophilicity of the PEG2-SF surface increased compared with that of SF. The attachment and growth of fibroblast cells (L-929) on the matrix of PEG2-SF were studied by a cell culture method. PEG2-SF exhibited very low cell attachment and growth, though SF exhibited high cell attachment and growth. The filopodium of the cells attached to PEG2-SF could not be found, and the cells aggregated to form masses in scanning electron microscopy images. These results could be explained in terms of the increased hydrophilicity of the PEG2-SF surface.

  5. Synthesis, rotational dynamics, and photophysical characterization of a crystalline linearly conjugated phenyleneethynylene molecular dirotor.

    Science.gov (United States)

    Hughs, Melissa; Jimenez, Miguel; Khan, Saeed; Garcia-Garibay, Miguel A

    2013-06-07

    We report the synthesis, crystal structure, solid-state dynamics, and photophysical properties of 6,13-bis((4-(3-(3-methoxyphenyl)-3,3-diphenylprop-1-yn-1-yl)phenyl)ethynyl)-5,7,12,14-tetrahydro-5,14:7,12-bis([1,2]benzeno)pentacene (1), a molecular dirotor with a 1,4-bis((4-ethynylphenyl)ethynyl)benzene (BEPEB) chromophore. The incorporation of a pentiptycene into the molecular dirotor provides a central stator and a fixed phenylene ring relative to which the two flanking ethynylphenylene rotators can explore various torsion angles; this allows the BEPEB fluorophore dynamics to persist in the solid state. X-ray diffraction studies have shown that molecular dirotor 1 is packed so that all the BEPEB fluorophores adopt a parallel alignment, this is ideal for the development of functional materials. Variable temperature, quadrupolar echo (2)H NMR studies have shown that phenylene rotator flipping has an activation energy of 9.0 kcal/mol and a room temperature flipping frequency of ∼2.6 MHz. Lastly, with measurements in solution, glasses, and crystals, we obtained evidence that the fluorescence excitation and emission spectra of the phenyleneethynylene chromophores is dependent on the extent of conjugation between the phenylene rings, as determined by their relative dihedral angles. This work provides a promising starting point for the development of molecular dirotors with polar groups whose amphidynamic nature will allow for the rapid shifting of solid-state absorption, fluorescence, and birefringence, in response to external electric fields.

  6. Ring Walking/Oxidative Addition Reactions for the Controlled Synthesis of Conjugated Polymers

    Energy Technology Data Exchange (ETDEWEB)

    Bazan, Guillermo C

    2012-04-03

    Power conversion efficiencies of plastic solar cells depend strongly on the molecular weight characteristics of the semiconducting polymers used for their fabrication. The synthesis of these materials typically relies on transition metal mediated catalytic reactions. In many instances, the ideal structures cannot be attained because of deficiencies in these reactions, particularly when it comes to being able to achieve high number average molecular weights and narrow molecular weight distributions. Another important conjugated polymer structure of interest is one in which a single functional group is attached at the end group of the chain. Such systems would be ideal for modifying surface properties at interfaces and for labeling biomolecular probes used in fluorescent biosensors. To respond to the challenges above, our efforts have centered on the design of homogenous transition metal complexes that are easy to prepare and effective in carrying out living, or quasi-living, condensative chain polymerization reactions. The key mechanistic challenge for the success of this reaction is to force the insertion of one monomer unit at a time via a process that involves migration of the transition metal-containing fragment to one terminus of the polymer chain. Chain growth characteristics are therefore favored when the metal does not dissociate from the newly formed reductive elimination product. We have proposed that dissociation is disfavored by the formation of a -complex, in which the metal can sample various locations of the electronically delocalized framework, a process that we term ring-walking , and find the functionality where oxidative addition takes place. Success has been achieved in the nickel-mediated cross coupling reaction of Grignard reagents with aromatic halides by using bromo[1,2-bis(diphenylphosphino)ethane]phenylnickel. This reagent can yield poly(thiophene)s (one of the most widely used type of polymer in plastic solar cells) with excellent

  7. Synthesis and Chromatography-Free Purification of PNA-PEO Conjugates for the Functionalisation of Gold Sensors

    Directory of Open Access Journals (Sweden)

    Filippo Romanato

    2012-09-01

    Full Text Available Peptide Nucleic Acids (PNAs linked to high molecular weight (MW poly(ethylene oxide (PEO derivatives could be useful conjugates for the direct functionalisation of gold surfaces dedicated to Surface Plasmon Resonance (SPR-based DNA sensing. However their use is hampered by the difficulty to obtain them through a convenient and economical route. In this work we compared three synthetic strategies to obtain PNA-high MW PEO conjugates composed of (a a 15-mer PNA sequence as the probe complementary to genomic DNA of Mycobacterium tuberculosis, (b a PEO moiety (2 or 5 KDa MW and (c a terminal trityl-protected thiol necessary (after acidic deprotection for grafting to gold surfaces. The 15-mer PNA was obtained by solid-phase synthesis. Its amino terminal group was later condensed to bi-functional PEO derivatives (2 and 5 KDa MW carrying a Trt-cysteine at one end and a carboxyl group at the other end. The reaction was carried out either in solution, using HATU or PyOxim as coupling agents, or through the solid-phase approach, with 49.6%, 100% and 5.2% yield, respectively. A differential solvent extraction strategy for product purification without the need for chromatography is described. The ability of the 5 KDa PEO conjugate to function as a probe for complementary DNA detection was demonstrated using a Grating-Coupling Surface Plasmon Resonance (GC-SPR system. The optimized PEO conjugation and purification protocols are economical and simple enough to be reproduced also within laboratories that are not highly equipped for chemical synthesis.

  8. Synthesis and evaluation of the antioxidative potential of minoxidil-polyamine conjugates.

    Science.gov (United States)

    Hadjipavlou-Litina, Dimitra; Magoulas, George E; Bariamis, Stavros E; Tsimali, Zinovia; Avgoustakis, Konstantinos; Kontogiorgis, Christos A; Athanassopoulos, Constantinos M; Papaioannou, Dionissios

    2013-07-01

    A series of conjugates (MNX-CO-PA) of minoxidil (MNX) with the polyamines (PAs) putrescine (PUT), spermidine (SPD) and spermine (SPM) as well as dopamine were produced through activation of MNX with N,N'-carbonyldiimidazole, followed by reaction with dopamine or selectively protected PAs and acid-mediated deprotection. These conjugates together with conjugates of the general type MNX-PA or PA-MNX-PA, readily produced using literature protocols, were tested as antioxidants. The most potent inhibitors of lipid peroxidation were the conjugates MNX-SPM (2, 94%), SPM-MNX-SPM (4, 94%) and MNX-N(4)-SPD (7, 91%) and MNX (91%). The most powerful lipoxygenase (LOX) inhibitors were MNX (IC50 = 20 μM) and the conjugates MNX-N(8)-SPD (9, IC50 = 22.1 μM), MNX-CO-dopamine (11, IC50 = 28 μM) and MNX-N(1)-SPD (8, IC50 = 30 μM). The most interesting conjugates 2, MNX-CO-PUT (5), 8 and 11 as well as MNX were generally found to exhibit weaker (22-36.5%) or no (conjugate 8) anti-inflammatory activity than indomethacin (47%) with the exception of MNX which showed almost equal potency (49%) to indomethacin. The cytocompatibility of conjugates and MNX at the highest concentration of 100 μM showed a survival percentage of 87-107%, with the exception of conjugates with SPM (compound 2) and MNX-CO-SPM (6), which showed considerable cytotoxicity (survival percentage 8-14%). Molecular docking studies were carried on conjugate 9 and the parent compound MNX and were found to be in accordance with our experimental biological results. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Isomerization of all-(E)-Retinoic Acid Mediated by Carbodiimide Activation - Synthesis of ATRA Ether Lipid Conjugates

    DEFF Research Database (Denmark)

    Christensen, Mikkel Stochkendahl; Pedersen, Palle Jacob; Andresen, Thomas Lars

    2010-01-01

    Treatment of the lysolipid 1-O-hexadecyl-sn-phosphatidylcholine with all-(E)-retinoic acid, DCC and DMAP resulted in poor acylation and caused (Z)/(E) isomerization of the alpha-beta double bond. In the presence of a proton source, the carbodiimide-activated all-(E)-retinoic acid undergoes fast...... isomerization to give a final mixture of (13E)/(13Z) isomers in a 3:1 ratio. Similar treatment of (13Z)-retinoic acid leads to the same isomer ratio. The isomerization was circumvented successfully by using a Mitsunobu reaction, which provided an efficient synthesis of all-(E)-retinoic acid sn-2-conjugated...

  10. Synthesis and in vitro antiplasmodial evaluation of 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone conjugates.

    Science.gov (United States)

    Raj, Raghu; Saini, Anu; Gut, Jiri; Rosenthal, Philip J; Kumar, Vipan

    2015-05-05

    The manuscript describes the synthesis of novel amide tethered 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone bifunctional hybrids and their evaluation as antimalarial agents against W2 resistant strain of Plasmodium falciparum. The antiplasmodial activity of 7-chloroquinoline-ferrocenylchalcones was found to be less than their corresponding simple chalcone conjugates. The presence of a methoxy substituent at para position of ring B on chalcones and longer alkyl chain length markedly improved the antiplasmodial profiles of the synthesized scaffolds with the most potent of the test compound exhibiting an IC50 value of 17.8 nM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Synthesis, characterization, and in vivo efficacy evaluation of PGG–docetaxel conjugate for potential cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Jiang X

    2012-02-01

    Full Text Available Danbo Yang1, Sang Van2, Yingyi Shu1, Xiaoqing Liu1, Yangfeng Ge1, Xinguo Jiang3, Yi Jin2, Lei Yu1,21Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People’s Republic of China; 2Biomedical Group, Nitto Denko Technical Corporation, CA, USA; 3School of Pharmacy, Fudan University, Shanghai, People’s Republic of ChinaAim: This work is intended to develop and evaluate a biopolymeric poly(L-γ-glutamyl-glutamine (PGG–docetaxel (DTX conjugate that can spontaneously self-assemble in aqueous solutions to become nanoparticles.Methods: DTX was covalently attached to hydrophilic PGG by direct esterification, and the conjugate was characterized by proton nuclear magnetic resonance spectroscopy, molecular weight gel permeation chromatography, solubility, size distribution and morphology, and hemolysis. Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. Dynamic light scattering, transmission electron microscopy, and atomic force microscopy revealed the particle size, distribution and morphology of the PGG–DTX conjugate. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460.Results: Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. The conjugate formed nanoparticles with an average diameter of 30 nm in spherical shape and unimodal particle size distribution. The conjugate exhibited about 2% hemolysis at 10 mg/mL, compared with 56% for Tween 80® at 0.4 mg/mL, and 33% for Cremophor EL® at 10 mg/mL. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460. As expected, conjugated DTX exhibited lower cytotoxicity compared to that of free DTX, in concentration

  12. Controllable synthesis of protein-conjugated lead sulfide nanocubes by using bovine hemoglobin as a capping agent

    Science.gov (United States)

    Yang, Guangrui; Qin, Dezhi; Zhang, Li

    2014-06-01

    A simple, convenient, and controllable strategy was reported in this contribution for protein-assisted synthesis BHb-conjugated PbS nanocubes. Powder X-ray diffraction, energy disperse X-ray spectroscopy, transmission electron microscopy, high-resolution transmission electron microscopy, and selected-area electron diffraction characterizations were used to determine the structure and morphology of BHb-conjugated PbS nanocubes. The prepared PbS nanocrystals with cubic rock salt structure were uniform and monodispersed with homogeneous size around 12 nm. The results of Fourier transform infrared and circular dichroism assay proved that Pb2+/PbS had coordination interaction with functional groups of BHb besides physical-binding effect, and the secondary structure of protein significantly changed with this interaction. Thermogravimetric analysis results confirmed the existence of BHb in PbS nanocrystals and indicated that the conjugate bonds existed between PbS and BHb. A clear perspective was shown here that special nanostructure could be created by using proteins as a mediating template at the inorganic-organic interface.

  13. Synthesis and in vitro evaluation of PNA-peptide-DETA conjugates as potential cell penetrating artificial ribonucleases.

    Science.gov (United States)

    Petersen, Lene; de Koning, Martijn C; van Kuik-Romeijn, Petra; Weterings, Jimmy; Pol, Christine J; Platenburg, Gerard; Overhand, Mark; van der Marel, Gijsbert A; van Boom, Jacques H

    2004-01-01

    We report the synthesis of novel artificial ribonucleases with potentially improved cellular uptake. The design of trifunctional conjugates 1a and 1b is based on the specific RNA-recognizing properties of PNA, the RNA-cleaving abilities of diethylenetriamine (DETA), and the peptide (KFF)(3)K for potential uptake into E. coli. The conjugates were assembled in a convergent synthetic route involving native chemical ligation of a PNA, containing an N-terminal cysteine, with the C-terminal thioester of the cell-penetrating (KFF)(3)K peptide to give 12a and 12b. These hybrids contained a free cysteine side-chain, which was further functionalized with an RNA-hydrolyzing diethylenetriamine (DETA) moiety. The trifunctional conjugates (1a, 1b) were evaluated for RNA-cleaving properties in vitro and showed efficient degradation of the target RNA at two major cleavage sites. It was also established that the cleavage efficiency strongly depended on the type of spacer connecting the PNA and the peptide.

  14. Thiophene in Conducting Polymers: Synthesis of Poly(thiophene)s and Other Conjugated Polymers Containing Thiophenes, for Application in Polymer Solar Cells

    DEFF Research Database (Denmark)

    Livi, Francesco; Carlé, Jon Eggert; Bundgaard, Eva

    2015-01-01

    Conducting polymers based on thiophene are described. The polymers include poly(thiophene) with and without side-chains and other conjugated polymers in general, based on thiophene. The synthesis and characteristics of the polymers are described along with the application of these as light-absorb......-absorbing materials in polymer solar cells.......Conducting polymers based on thiophene are described. The polymers include poly(thiophene) with and without side-chains and other conjugated polymers in general, based on thiophene. The synthesis and characteristics of the polymers are described along with the application of these as light...

  15. Synthesis and structural elucidation of glutathione and N-aceyl-cysteine conjugates of 5-aminosalicylic acid

    DEFF Research Database (Denmark)

    Jensen, J.; Cornett, Claus; Olsen, C. E.

    1993-01-01

    conjugates of 5-ASA and GSH were found to be formed. 5-ASA was initially oxidized by PbO2 in a solution of TRIS-HCl buffer pH 9.3 followed by the in situ addition of N-acetyl-cysteine or glutathione to the oxidized 5-ASA at pH 7.5. The resulting conjugates were N-acetylated at the aromatic amino group......The ability of 5-aminosalicylic acid (5-ASA) to be oxidized to a quinone monoimine compound capable of conjugating with nucleophilic compounds such as N-acetyl-cysteine (NAC) and glutathione (GSH) has been investigated in vitro. Three isomeric conjugates of 5-ASA and NAC as well as three isomeric...... dose of 5-ASA into mercapturic acids of 5-ASA, when 1 g of 5-ASA was ingested. In spite of the low detection limits, none of the mercapturic acid conjugates was detected in the urine from persons treated with 5-ASA....

  16. Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES: Synthesis, cytotoxicity and inclusion of anaesthetic actives

    Directory of Open Access Journals (Sweden)

    Lisa Markenstein

    2014-12-01

    Full Text Available The mono-6-deoxy-6-azides of 2,6-di-O-methyl-β-cyclodextrin (DIMEB and randomly methylated-β-cyclodextrin (RAMEB were conjugated to propargylated hydroxyethyl starch (HES by Cu+-catalysed [2 + 3] cycloaddition. The resulting water soluble polymers showed lower critical solution temperatures (LCST at 52.5 °C (DIMEB-HES and 84.5 °C (RAMEB-HES, respectively. LCST phase separations could be completely avoided by the introduction of a small amount of carboxylate groups at the HES backbone. The methylated CDs conjugated to the HES backbone exhibited significantly lower cytotoxicities than the corresponding monomeric CD derivatives. Since the binding potentials of these CD conjugates were very high, they are promising candidates for new oral dosage forms of anaesthetic actives.

  17. Design and multi-step synthesis of chalcone-polyamine conjugates as potent antiproliferative agents.

    Science.gov (United States)

    Rioux, Benjamin; Pouget, Christelle; Fidanzi-Dugas, Chloë; Gamond, Aurélie; Laurent, Aurélie; Semaan, Josiane; Pinon, Aline; Champavier, Yves; Léger, David Y; Liagre, Bertrand; Duroux, Jean-Luc; Fagnère, Catherine; Sol, Vincent

    2017-09-15

    The aim of this study is to synthesize chalcone-polyamine conjugates in order to enhance bioavailability and selectivity of chalcone core towards cancer cells, using polyamine-based vectors. 3-hydroxy-3',4,4',5'-tetramethoxychalcone (1) and 3',4,4',5'-tetramethoxychalcone (2) were selected as parent chalcones since they were found to be efficient anti-proliferative agents on various cancer cells. A series of ten chalcone-polyamine conjugates was obtained by reacting carboxychalcones with different polyamine tails. Chalcones 1 and 2 showed a strong cytotoxic activity against two prostatic cancer (PC-3 and DU-145) and two colorectal cancer (HT-29 and HCT-116) cell lines. Then, chalcone-spermine conjugates 7d and 8d were shown to be the most active of the series and could be considered as promising compounds for colon and prostatic cancer adjuvant therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. PEG-metronidazole conjugates: synthesis, in vitro and in vivo properties.

    Science.gov (United States)

    Bersani, Cinzia; Berna, Manuela; Pasut, Gianfranco; Veronese, Francesco Maria

    2005-09-01

    Metronidazole (MTZ), a drug used for the treatment of protozoal infections caused by protozoa and anaerobic microorganisms, was conjugated to linear or branched poly(ethylene glycol) of 5,000, 10,000 and 20,000 Da. An ester linkage between polymer and drug was used in the coupling to yield a polymeric prodrug. The modification allowed overcoming the known MTZ solubility problem leading us to obtain a bioconjugate more suitable for parental administration. The conjugates of various molecular weight polymers have been tested in vitro toward chemical degradation and digestive enzymes. It was found that molecular weight and shape of PEG is critical for the prodrugs stability. Good resistance in the stomach acidic media was found and a slow release of the drug in the large intestinal fluid may take place. In vivo studies carried out following i.v. or s.c. administration to mice revealed improved pharmacokinetics properties upon conjugation.

  19. Synthesis of minoxidil conjugates and their evaluation as HL-60 differentiation agents.

    Science.gov (United States)

    Stoica, Sonia; Magoulas, George E; Antoniou, Antonia I; Suleiman, Sherif; Cassar, Analisse; Gatt, Lucienne; Papaioannou, Dionissios; Athanassopoulos, Constantinos M; Schembri-Wismayer, Pierre

    2016-02-15

    Activation of minoxidil (MNX) with N,N'-carbonyldiimidazole and coupling with natural polyamines (PAs) and commercially available aliphatic or aromatic amines provided a series of new conjugates which were evaluated for their ability to induce differentiation to HL-60 acute myeloid leukemia cancer cells, using a modified NBTZ reduction test. Although neither MNX nor 4,4'-methylenedianiline (MDA) or 2,7-diaminofluorene (DAF), alone or in combination, had any effect, the MNX-spermine (SPM) conjugate (11) and the conjugates 7 and 8 of MNX with MDA and DAF exhibited a differentiation-inducing effect at a concentration of 10 μM without being toxic on proliferating human peripheral blood mononuclear cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Synthesis of aminobenzyltriethylenetetraaminohexaacetic acid: conjugation of the chelator to protein by an alkylamine linkage.

    Science.gov (United States)

    Bhargava, K K; Zhang, Z Y; Palestro, C J; Acharya, S A

    1999-10-01

    The conjugation of a chelating agent to an antibody as an anchoring site for a radionuclide is the first step in the successful preparation of a radiolabeled antibody for a diagnostic and therapeutic application. The high affinity of the protein bound chelator towards radionuclide ensures a higher selectivity in the delivery of the radionuclide to the targeted tissue. 4-Aminobenzylderivativetriethlenetetraaminohexaacetic acid (TTHA), a hexadentate chelating agent has been now prepared for conjugation with proteins in view of the higher affinity of TTHA metal ions as compared to DTPA. The latent crosslinking potential of alpha-hydroxy aldehydes has been used to conjugate the new chelating agent to proteins through an alkylamine linkage. On incubation of amino benzyl TTHA with glycoladehyde at neutral pH and room temperature, the reagent is converted to oxo ethyl amino benzyl TTHA. On addition of albumin to this reaction mixture, the oxo ethylamino benzyl TTHA generates reversible schiff base adducts with the amino groups of albumin. The reduction of the Schiff base adducts of the chelator with the protein by sodium cyanoborohydride stabilizes the schiff base adducts as stable alkylamine linkages. 4-Thiocyanatobenzyl TTHA has also been prepared and conjugated to albumin through a thiocarbamoyl linkage. Both preparations of TTHA conjugated albumin complexed with 99mTc and 111In, with high affinity and no decomposition of the complex was noticed for at least up to 6 hrs after the preparation. The radiolabels complexed with these TTHA -albumin conjugates could not be 'chased' out by free DTPA. A comparison of the biodistribution of 111In, bound to the TTHA conjugated through an alkylamine and a thiocarbamoyl linkage showed that 111In complexed with alkylamine linked TTHA was retained in blood to a level nearly 17% higher compared to that seen with thicarbamoyl linked TTHA, one hr after the injection into mice. Thus, the alkylamine linkage appears to be more stable under

  1. Synthesis, characterization and application of lipase-conjugated citric acid-coated magnetic nanoparticles for ester synthesis using waste frying oil.

    Science.gov (United States)

    Patel, Unisha; Chauhan, Kishor; Gupte, Shilpa

    2018-04-01

    In the present work, magnetic nanoparticles (MNPs) were prepared by chemical precipitation of trivalent and divalent iron ions which were functionalized using citric acid. The bacterial isolate Staphylococcus epidermidis KX781317 was isolated from oil-contaminated site. The isolate produced lipase, which was purified and immobilized on magnetic nanoparticles (MNPs) for ester synthesis from waste frying oil (WFO). The characterization of MNPs employed conventional TEM, XRD and FTIR techniques. TEM analysis of MNPs showed the particle size in the range of 20-50 nm. FTIR spectra revealed the binding of citric acid to Fe 3 O 4 and lipase on citric acid-coated MNPs. The citric acid-coated MNPs and lipase-conjugated citric acid-coated MNPs had similar XRD patterns which indicate MNPs could preserve their magnetic properties. The maximum immobilization efficiency 98.21% of lipase-containing citric acid-coated MNPs was observed at ratio 10:1 of Cit-MNPs:lipase. The pH and temperature optima for lipase conjugated with Cit-MNPs were 7 and 35 °C, respectively. Isobutanol was found to be an effective solvent for ester synthesis and 1:2 ratio of oil:alcohol observed significant for ester formation. The ester formation was determined using TLC and the % yield of ester conversion was calculated. The rate of ester formation is directly proportional to the enzyme load. Formed esters were identified as isobutyl laurate ester and isobutyl myristate ester through GC-MS analysis.

  2. Synthesis and characterization of pi-extended bowl-shaped pi-conjugated molecules.

    Science.gov (United States)

    Amaya, Toru; Mori, Koichi; Wu, Hsyueh-Liang; Ishida, Satoshi; Nakamura, Jun-ichi; Murata, Kazuhiko; Hirao, Toshikazu

    2007-05-21

    A series of pi-extended bowl-shaped pi-conjugated compounds were synthesized from sumanene and characterized, and among them the terthiophene derivative showed a remarkable red-shifted absorption and small band gap, which wa rationalized by molecular orbital calculation.

  3. NEOGLYCOPROTEINS AS CARRIERS FOR ANTIVIRAL DRUGS - SYNTHESIS AND ANALYSIS OF PROTEIN DRUG CONJUGATES

    NARCIS (Netherlands)

    Molema, Grietje; Jansen, Robert W.; Visser, Jan; Herdewijn, Piet; Moolenaar, Frits; Meijer, Dirk K.F.

    In order to investigate whether neoglycoproteins can potentially act as carriers for targeting of antiviral drugs to certain cell types in the body, various neoglycoproteins were synthesized using thiophosgene-activated p-aminophenyl sugar derivatives. These neoglycoproteins were conjugated with the

  4. Synthesis of highly stable folic acid conjugated magnetite nanoparticles for targeting cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mohapatra, S [Department of Chemistry, Indian Institute of Technology, Kharagpur, 721302 (India); Mallick, S K [Department of Biotechnology, Indian Institute of Technology, Kharagpur, 721302 (India); Maiti, T K [Department of Biotechnology, Indian Institute of Technology, Kharagpur, 721302 (India); Ghosh, S K [Department of Biotechnology, Indian Institute of Technology, Kharagpur, 721302 (India); Pramanik, P [Department of Chemistry, Indian Institute of Technology, Kharagpur, 721302 (India)

    2007-09-26

    A new approach towards the design of folic acid conjugated magnetic nanoparticles for enhancing their site specific intracellular uptake against a folate receptor overexpressing cancer cells is reported. Magnetite nanoparticles were prepared by coprecipitation from an Fe{sup 3+} and Fe{sup 2+} solution followed by surface modification with 2-carboxyethyl phosphonic acid to form carboxyl group terminated nanoparticles. Then folic acid and fluorescein isothiocyanate (FITC) were conjugated with carboxylic acid functionalized magnetite nanoparticles using 2,2'-(ethylenedioxy)-bis-ethylamine. These folate-conjugated nanoparticles were characterized in terms of their size by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Surface functional groups and surface composition were analyzed by Fourier transform infrared (FTIR) spectroscopy and x-ray photoelectron spectroscopy (XPS), respectively. Vibration sample magnetometry (VSM) measurements showed the superparamagnetic nature of the particles at room temperature. Folate-conjugated magnetic nanoparticles are noncytotoxic and receptor mediated internalization by HeLa and B16 melanoma F0 cancer cells was confirmed by flow cytometry and confocal microscopy.

  5. Synthesis and biological evaluations of cytotoxic and antiangiogenic triterpenoids-jacaranone conjugates

    DEFF Research Database (Denmark)

    Sun, Hua; Yue, Partick Y. K.; Wang, Shao Rong

    2016-01-01

    showed that these conjugates are more potent in both cytotoxic and antiangiogenic assays than their corresponding parent molecules, and are also selectively more active against melanoma cells B16 and metastatic B16BL6 than the two other cancer cell lines (A549 and MCF-7) tested. The predicted...

  6. Cu(I)-catalyzed efficient synthesis of 2′-Triazolo-nucleoside conjugates

    DEFF Research Database (Denmark)

    Mathur, D.; Rana, N.; Olsen, Carl Erik

    2015-01-01

    -nucleoside conjugates, which can be evaluated for different biological activity for suitable drug development, were unambiguously identified on the basis of 1H NMR, 13C NMR, IR, and HRMS data analysis. These compounds have been synthesized for the first time and have not been reported in the literature earlier....

  7. Synthesis of highly stable folic acid conjugated magnetite nanoparticles for targeting cancer cells

    International Nuclear Information System (INIS)

    Mohapatra, S; Mallick, S K; Maiti, T K; Ghosh, S K; Pramanik, P

    2007-01-01

    A new approach towards the design of folic acid conjugated magnetic nanoparticles for enhancing their site specific intracellular uptake against a folate receptor overexpressing cancer cells is reported. Magnetite nanoparticles were prepared by coprecipitation from an Fe 3+ and Fe 2+ solution followed by surface modification with 2-carboxyethyl phosphonic acid to form carboxyl group terminated nanoparticles. Then folic acid and fluorescein isothiocyanate (FITC) were conjugated with carboxylic acid functionalized magnetite nanoparticles using 2,2'-(ethylenedioxy)-bis-ethylamine. These folate-conjugated nanoparticles were characterized in terms of their size by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Surface functional groups and surface composition were analyzed by Fourier transform infrared (FTIR) spectroscopy and x-ray photoelectron spectroscopy (XPS), respectively. Vibration sample magnetometry (VSM) measurements showed the superparamagnetic nature of the particles at room temperature. Folate-conjugated magnetic nanoparticles are noncytotoxic and receptor mediated internalization by HeLa and B16 melanoma F0 cancer cells was confirmed by flow cytometry and confocal microscopy

  8. Synthesis and two-photon absorption property of new π-conjugated ...

    Indian Academy of Sciences (India)

    mers containing π-deficient heterocycles like pyridine, pyran, and oxadiazoles show greater tendency to trans- port electrons than holes.12 Consequently, in order to have conjugated polymer with both hole and elec- tron transporting groups in a single chain, the donor– acceptor strategy is being widely used to tailor their.

  9. Synthesis of Donor-Acceptor Conjugated Polymers by "CLICK" Polymerization for OPV applications

    DEFF Research Database (Denmark)

    Brandt, Rasmus Guldbæk; Yu, Donghong

    The intent of this study was to utilize the Copper(I)-catalyzed Azide Alkyne Cycloaddition (CuAAC) as a polymerization technique (“Click” Polymerization) for synthesizing novel π-conjugated low band gap polymers for organic photovoltaic applications (OPV). The chosen approach was to synthesize...

  10. Pd(II)/Bipyridine-Catalyzed Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Carboxylic Acids. Synthesis of β-Quaternary Carbons Substituted Carboxylic Acids.

    Science.gov (United States)

    Liu, Rui; Yang, Zhenyu; Ni, Yuxin; Song, Kaixuan; Shen, Kai; Lin, Shaohui; Pan, Qinmin

    2017-08-04

    Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids (including β,β-disubstituted acrylic acids) was developed and optimized, which provided a mild and convenient method for the highly challenging synthesis of β-quaternary carbons substituted carboxylic acids.

  11. Thiophene in Conducting Polymers: Synthesis of Poly(thiophene)s and Other Conjugated Polymers Containing Thiophenes, for Application in Polymer Solar Cells

    DEFF Research Database (Denmark)

    Livi, Francesco; Carlé, Jon Eggert; Bundgaard, Eva

    2015-01-01

    Conducting polymers based on thiophene are described. The polymers include poly(thiophene) with and without side-chains and other conjugated polymers in general, based on thiophene. The synthesis and characteristics of the polymers are described along with the application of these as light......-absorbing materials in polymer solar cells....

  12. Nanodiamond-chymotrypsin and nanodiamond-papain conjugates, their synthesis and activity and visualization of their interaction with cells using optical and electron microscopy.

    Science.gov (United States)

    Golyshev, Sergey A; Berkovich, Anna K; Yakovlev, Ruslan Yu; Bystrov, Dmitry M; Ivanov, Nikita M; Balandina, Galina N; Rudenskaya, Galina N

    2017-07-28

    Two novel conjugates of detonation nanodiamonds (dNDs) with the proteolytic enzymes chymotrypsin and papain were synthesized. The synthesis was performed via functionalization of the dNDs' surface with acidic/alkali treatment followed by carbodiimide-mediated protein binding. Covalent binding of the enzymes was confirmed by Fourier transform infrared spectrographic analysis and high-performance liquid chromatography (HPLC) amino acid analysis. HPLC also proved the preservation of the enzymes' composition during synthesis. The same assay was used to determine the binding ratios. The ratios were 12% (mass to mass) for chymotrypsin and 7.4% for papain. The enzymatic activity of the conjugates was measured using chromogenic substrates and appeared to be approximately 40% of that of the native enzymes. The optimum pH values and stability under various conditions were determined. The sizes of resulting particles were measured using dynamic light scattering and direct electron microscopic observation. The enzyme conjugates were shown to be prone to aggregation, resulting in micrometer-sized particles. The ζ-potentials were measured and found to be positive for the conjugates. The conjugated enzymes were tested for biological activity using an in vitro model of cultured transformed human epithelial cells (HeLa cell line). It was shown that dND-conjugated enzymes effectively bind to the surface of the cells and that enzymes attack exposed proteins on the plasma membrane, including cell adhesion molecules. Incubation with conjugated enzymes results in morphological changes of the cells but does not affect cell viability, as judged by monitoring the cell division index and conducting ultrastructural studies. dNDs are internalized by the cells via endocytosis, being enclosed in forming coated vesicles by chance, and they accumulate in single membrane-bound vacuoles, presumably late endosomes/phagosomes, along with multimembranous onionlike structures. The authors propose a

  13. Synthesis of lysozyme-metallacarborane conjugates and the effect of boron cluster modification on protein structure and function.

    Science.gov (United States)

    Kowalski, Konrad; Goszczyński, Tomasz; Leśnikowski, Zbigniew J; Boratyński, Janusz

    2015-02-09

    Two complementary methods, "in solution" and "in solid state", for the synthesis of lysozyme modified with metallacarborane (cobalt bis(dicarbollide), Co(C2 B9 H11 )2 (2-) ) were developed. As metallacarborane donors, oxonium adducts of cobalt bis(dicarbollide) and 1,4-dioxane or tetrahydropyran were used. The physicochemical and biochemical properties of the obtained lysozyme-metallacarborane conjugates were studied for changes in secondary and tertiary structure, aggregation behavior, and biological activity. Only minor changes in primary, secondary, and tertiary protein structure were observed, caused by the single substitution of metallacarborane on lysozyme. However, the modification produced significant changes in lysozyme enzymatic activity and a tendency toward time- and temperature-dependent aggregation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Synthesis of a conjugated pyrrolopyridazinedione–benzodithiophene (PPD–BDT) copolymer and its application in organic and hybrid solar cells

    KAUST Repository

    Knall, Astrid-Caroline

    2017-03-30

    Herein, we describe the synthesis and characterization of a conjugated donor–acceptor copolymer consisting of a pyrrolopyridazinedione (PPD) acceptor unit, and a benzodithiophene (BDT) donor unit. The polymerization was done via a Stille cross-coupling polycondensation. The resulting PPD–BDT copolymer revealed an optical bandgap of 1.8 eV and good processability from chlorobenzene solutions. In an organic solar cell in combination with PC70BM, the polymer led to a power conversion efficiency of 4.5%. Moreover, the performance of the copolymer was evaluated in polymer/nanocrystal hybrid solar cells using non-toxic CuInS2 nanocrystals as inorganic phase, which were prepared from precursors directly in the polymer matrix without using additional capping ligands. The PPD–BDT/CuInS2 hybrid solar cells showed comparably high photovoltages and a power conversion efficiency of 2.2%.Graphical abstract

  15. Novel two-step synthesis of gold nanoparticles capped with bile acid conjugates

    Energy Technology Data Exchange (ETDEWEB)

    Noponen, Virpi [University of Jyvaeskylae, Department of Chemistry, P.O. Box 35, FIN-40014 University of Jyvaeskylae (Finland); Bhat, Shreedhar [Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012 (India); Sievaenen, Elina [University of Jyvaeskylae, Department of Chemistry, P.O. Box 35, FIN-40014 University of Jyvaeskylae (Finland)], E-mail: elvirtan@jyu.fi; Kolehmainen, Erkki [University of Jyvaeskylae, Department of Chemistry, P.O. Box 35, FIN-40014 University of Jyvaeskylae (Finland)

    2008-08-01

    Bile acids and their conjugates are physiologically important molecules. Syntheses and structure elucidation combined with investigation of properties and applications of bile acids and their derivatives are of academic interest. The concept of using bile acids and their conjugates in nanoscience is a novel idea, which opens up fascinating prospects. In this article, an easy and simple route for obtaining N-lithocholyl-L-(cysteine ethyl ester) (3), capable of effectively capping and stabilizing metal nanoparticles, is described. The whole synthetic route needs only two steps giving a moderate to good yield. The gold NPs are characterized by elemental analysis, UV spectroscopy, and TEM. Additionally, {sup 13}C CP/MAS NMR studies for different ligand/Au ratios have been performed.

  16. Novel HPC-ibuprofen conjugates: synthesis, characterization, thermal analysis and degradation kinetics

    International Nuclear Information System (INIS)

    Hussain, M.A.; Lodhi, B.A.; Abbas, K.

    2014-01-01

    Naturally occurring hydrophilic polysaccharides are advantageously used as drug carriers because they provide a mechanism to improve drug action. Hydroxypropylcellulose (HPC) is water-soluble, biocompatible and bears hydroxyl groups for drug conjugation outside the parent polymeric chains. This unique geometry allows the attachment of drug molecules with higher covalent loading. The HPC-Ibuprofen conjugates as macromolecular prodrugs were therefore synthesized employing homogenous and one pot reaction methodologies using p-toluenesulfonyl chloride in N,N-dimethylacetamide solvent at 80 degree C for 24 h under nitrogen atmosphere. The imidazole was used as a base for neutralization of acidic impurities. Present strategy appeared effective to get high yield (77-81%) and high degree of drug substitution (DS 0.88-1.40) onto the HPC polymer as determined by the acid-base titration and verified by 1H-NMR spectroscopy. The gel permeation chromatography has shown uni-modal absorption which indicates no significant degradation of polymer during reaction. Macromolecular prodrugs with different DS of ibuprofen were synthesized, purified, characterized and found soluble in organic solvents. From thermogravimetric analysis, initial, maximum and final degradation temperatures of the conjugates were calculated and compared for relative thermal stability. Thermal degradation kinetics was also studied and results have indicated that degradation of conjugates follows about first order kinetics as calculated by Kissinger model. The energy of activation was also found moderate 92.38, 99.34 and 87.34 kJ/mol as calculated using Friedman, Broido and Chang models. It was found that these novel prodrugs of ibuprofen were thermally stable therefore these may have potential pharmaceutical applications. (author)

  17. Synthesis of metalloporphyrin-based conjugated microporous polymer spheres directed by bipyridine-type ligands.

    Science.gov (United States)

    Ji, Guipeng; Yang, Zhenzhen; Zhao, Yanfei; Zhang, Hongye; Yu, Bo; Xu, Jilei; Xu, Huanjun; Liu, Zhimin

    2015-04-30

    Zinc porphyrin (TP-Zn)-based conjugated microporous polymer (Zn-CMP) spheres were obtained via Sonagashira-Hagihara cross coupling reactions between 5,10,15,20-tetrakis(4-ethynylphenyl)porphyrin-Zn(II) and brominated monomers directed by bidentate bipyridine (BP)-type ligands for the first time, and the sphere diameters could be adjusted from 320 to 740 nm. The coordination between BP and TP-Zn was proved to be the key to forming spheres.

  18. Natural dendrimers: Synthesis and in vitro characterization of glycogen-cysteamine conjugates.

    Science.gov (United States)

    Perrone, Mara; Lopedota, Angela; Liberati, Elisa; Russo, Vincenzo; Cutrignelli, Annalisa; Laquintana, Valentino; de Sousa, Irene Pereira; Franco, Massimo; Tongiani, Serena; Denora, Nunzio; Bernkop-Schnürch, Andreas

    2017-06-01

    The aim of this study was to synthesize, characterize and evaluate the mucoadhesive properties of the first thiolated hyperbranched natural polysaccharide with biodegradability and biocompatibility features. In detail, glycogen-cysteamine conjugates were synthesized through a first step of oxidative ring opening applying increasing concentrations of sodium periodate, to obtain polymers with different degrees of oxidation, and a second step of reductive amination with a constant amount of cysteamine. The obtained glycogen-cysteamine conjugates were characterized regarding their content of free and total thiol groups by Ellman's assay, biocompatibility, swelling/erosion behavior, rheological synergism and mucoadhesive properties in comparison to the unmodified glycogen. The higher the concentration of periodate was, the higher was the content of total thiol groups being in the range of 255.7±12-1194.5±82μmol/g, biocompatibility remained unaffected by these structural changes. On the contrary, the mucoadhesive properties, evaluated by tensile, rheological synergism and rotating cylinder studies, appear to be influenced by the thiol groups concentration on the glycogen. In particular the glycogen-cysteamine conjugate exhibiting the highest degree of thiolation showed a 79-fold increase in viscosity over a time period of 8h, as well as, remained attached on freshly excised porcine mucosa 32-fold longer than the unmodified polymer. The higher was the amount of conjugated thiol groups, the higher was the water absorption capacity of glycogen-cysteamine tablets in Simulated Intestinal Fluid pH 6.8 (SIF). The introduction of thiol moieties on polymer changed the characteristics of the polysaccharide by improving mucoadhesion properties. Therefore, this work represents the first study describing thiolated natural dendrimers as potential platform useful to realize appropriate mucoadhesive nanocarrier systems suitable to prolong mucosal residence time. Copyright © 2017

  19. Synthesis of graphene-conjugated polymer nanocomposites for electronic device applications.

    Science.gov (United States)

    Qi, Xiaoying; Tan, Chaoliang; Wei, Jun; Zhang, Hua

    2013-02-21

    Graphene-based polymer nanocomposites have attracted increasing interest because of their superior physicochemical properties over polymers. Semiconductor conjugated polymers (CPs) with excellent dispersibility and stability, and efficient electronic and optical properties have been recently integrated with graphene to form a new class of functional nanomaterials. In this minireview, we will summarize the recent advances in the development of graphene-CP nanocomposites for electronic device applications.

  20. Synthesis and properties of poly[N-(2-hydroxypropyl) methacrylamide] conjugates of superoxide dismutase

    Czech Academy of Sciences Publication Activity Database

    Šubr, Vladimír; Etrych, Tomáš; Ulbrich, Karel; Hirano, T.; Kondo, T.; Todoroki, T.; Jelínková, Markéta; Říhová, Blanka

    2002-01-01

    Roč. 17, č. 2 (2002), s. 105-122 ISSN 0883-9115 R&D Projects: GA ČR GV307/96/K226 Institutional research plan: CEZ:AV0Z4050913 Keywords : poly[N-(2-hydroxypropyl)methacrylamide] conjugates * superoxide dismutase * ischemic/reperfusion injury Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.525, year: 2002

  1. Synthesis, Characterization, and Biodistribution of Quantum Dot-Celecoxib Conjugate in Mouse Paw Edema Model

    Directory of Open Access Journals (Sweden)

    Suresh K. Kalangi

    2018-01-01

    Full Text Available Increased risk of cardiovascular side effects has been reported with many of the drugs in the market, including nonsteroidal anti-inflammatory drugs (NSAIDs. Hence, it is critical to thoroughly evaluate the biodistribution and pharmacokinetic properties of the drugs. Presently nanotechnology in combination with noninvasive imaging techniques such as magnetic resonance imaging (MRI, computed axial tomography (CAT, and positron emission tomography (PET provides a better estimate of the spatio-temporal distribution of therapeutic molecules. Optical imaging using quantum dot- (QD- tagged biological macromolecules is emerging as a fast, economical, sensitive, and safer alternative for theranostic purposes. In the present study, we report the nanoconjugates of mercaptopropionic acid- (MPA- capped CdTe quantum dots (QDs and Celecoxib for bio-imaging in carrageenan-induced mouse paw edema model of inflammation. QD-Celecoxib conjugates were characterized by fluorescence, FT-IR, NMR, and zeta-potential studies. In vivo imaging of QD-Celecoxib conjugates showed clear localization in the inflamed tissue of mouse paw within 3 h, with a gradual increase reaching a maximum and a later decline. This decrease of fluorescence in the paw region is followed by an increase in urinary bladder region, suggesting the possible excretion of QD-drug conjugates from mice within 24 h.

  2. Synthesis and Properties of 1,8-Carbazole-Based Conjugated Copolymers

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Michinobu

    2010-07-01

    Full Text Available A new series of conjugated carbazole polymers based on the 1,8-carbazolylene unit was synthesized by the Pd-catalyzed polycondensation between the 1,8-diiodocarbazole derivative and various bifunctional counter comonomers. An alkyne spacer was found to be a key to increasing the molecular weight of the resulting polymers. All the obtained polymers showed good solubilities in the common organic solvents, and they were fully characterized by Gel permeation chromatography (GPC, and 1H NMR and infrared (IR spectroscopies. The UV-vis absorption and fluorescence spectra revealed the relationship between the chemical structure and effective conjugation length. The efficiency order of the carbazole connectivity was 2,7-carbazolylene > 1,8-carbazolylene > 3,6-carbazolylene. The electrochemical properties of these polymers suggested the relatively facile oxidation at ca. +0.5–0.7 V vs. Fc/Fc+ or a high potential as p-type semiconductors. The combination of the electrochemical oxidation potentials and the optical band gaps allowed us to estimate the HOMO and LUMO levels of the polymers. It was shown that the energy levels of the 1,8-carbazole-based conjugated polymers can be tunable by selecting the appropriate comonomer structures.

  3. Nanoarmored Enzymes for Organic Enzymology: Synthesis and Characterization of Poly(2-Alkyloxazoline)-Enzyme Conjugates.

    Science.gov (United States)

    Leurs, Melanie; Tiller, Joerg C

    2017-01-01

    The properties of enzymes can be altered significantly by modification with polymers. Numerous different methods are known to obtain such polymer-enzyme conjugates (PECs). However, there is no universal method to render enzymes into PECs that are fully soluble in organic solvents. Here, we present a method, which achieves such high degree of modification of proteins that the majority of modified enzymes will be soluble in organic solvents. This is achieved by preparing poly(2-alkyloxazoline)s (POx) with an NH 2 end group and coupling this functional polymer via pyromellitic acid dianhydride onto the amino groups of the respective protein. The resulting PECs are capable of serving as surfactants for unmodified proteins, rendering the whole mixture organosoluble. Depending on the nature of the POx and the molecular weight and the nature of the enzyme, the PECs are soluble in chloroform or even toluene. Another advantage of this method is that the poly(2-alkyloxazoline) can be activated with the coupling agent and used for the enzyme conjugation without further purification. The POx-enzyme conjugates generated by this modification strategy show modulated catalytic activity in both, aqueous and organic, systems. © 2017 Elsevier Inc. All rights reserved.

  4. Synthesis of different heterocycles-linked chalcone conjugates as cytotoxic agents and tubulin polymerization inhibitors.

    Science.gov (United States)

    Shankaraiah, Nagula; Nekkanti, Shalini; Brahma, Uma Rani; Praveen Kumar, Niggula; Deshpande, Namrata; Prasanna, Daasi; Senwar, Kishna Ram; Jaya Lakshmi, Uppu

    2017-09-01

    A series of new heterocycles-linked chalcone conjugates has been designed and synthesized by varying different alkane spacers. These conjugates were tested for their in vitro cytotoxic potential against a panel of selected human cancer cell lines namely, lung (A549 and NCI-H460), prostate (DU-145 and PC-3), colon (HCT-15 and HCT-116), and brain (U-87 glioblastoma) by MTT assay. Notably, among all the tested compounds, 4a exhibited potent cytotoxicity on NCI-H460 (lung cancer) cells with IC 50 of 1.48±0.19µM. The compound 4a showed significant inhibition of tubulin polymerization and disruption of the formation of microtubules (IC 50 of 9.66±0.06μM). Moreover, phase contrast microscopy and DAPI staining studies indicated that compound 4a can induce apoptosis in NCI-H460 cells. Further, the flow-cytometry analysis revealed that compound 4a arrests NCI-H460 cells in the G2/M phase of the cell cycle. In addition, molecular docking studies of the most active compounds 4a and 4b into the colchicine site of the tubulin, revealed the possible mode of interaction by these new conjugates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

    Directory of Open Access Journals (Sweden)

    Artur Jabłoński

    2017-11-01

    Full Text Available Fluorescent pyrene–linker–nucleobase (nucleobase = thymine, adenine conjugates with carbonyl and hydroxy functionalities in the linker were synthesized and characterized. X-ray single-crystal structure analysis performed for the pyrene–C(OCH2CH2–thymine (2 conjugate reveals dimers of molecules 2 stabilized by hydrogen bonds between the thymine moieties. The photochemical characterization showed structure-dependent fluorescence properties of the investigated compounds. The conjugates bearing a carbonyl function represent weak emitters as compared to compounds with a hydroxy function in the linker. The self-assembly properties of pyrene nucleobases were investigated in respect to their binding to single and double strand oligonucleotides in water and in buffer solution. In respect to the complementary oligothymidine T10 template in water, compounds 3 and 5 both show a self-assembling behavior according to canonical base–base pairing. However, in buffer solution, derivative 5 was much more effective than 3 in binding to the T10 template. Furthermore the adenine derivative 5 binds to the double-stranded (dA10–T10 template with a self-assembly ratio of 112%. Such a high value of a self-assembly ratio can be rationalized by a triple-helix-like binding, intercalation, or a mixture of both. Remarkably, compound 5 also shows dual staining pattern in living HeLa cells. Confocal microscopy confirmed that 5 predominantly stains mitochondria but it also accumulates in the nucleoli of the cells.

  6. Synthesis and anti-angiogenic effect of conjugates between serum albumin and non-steroidal anti-inflammatory drugs

    DEFF Research Database (Denmark)

    Kjaer, B; Struve, C; Friis, T

    2010-01-01

    of investigating the anti-angiogenic efficiency of NSAID-HSA conjugates in vitro, three NSAIDs, aspirin, ibuprofen, and naproxen were conjugated to HSA using different concentrations of their N-hydroxysuccinimide esters. Conjugation ratios from 10 to 50 were achieved and the conjugates retained a growth inhibitory...

  7. Inhibition of ATP synthesis by fenbufen and its conjugated metabolites in rat liver mitochondria

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-01-01

    in inhibiting ATP synthesis. Fenbufen showed time and concentration dependent inhibition of ATP synthesis with Kinact of 4.4 min(-1) and KI of 0.88 μM and Kinact/KI ratio of 5.01 min(-1) μM(-1). Data show that fenbufen did not act through opening MPT pore, nor did incubation of mitochondria with reduced GSH...

  8. Synthesis, Biological Activity and Preliminary in Silico ADMET Screening of Polyamine Conjugates with Bicyclic Systems.

    Science.gov (United States)

    Szumilak, Marta; Galdyszynska, Malgorzata; Dominska, Kamila; Bak-Sypien, Irena I; Merecz-Sadowska, Anna; Stanczak, Andrzej; Karwowski, Boleslaw T; Piastowska-Ciesielska, Agnieszka W

    2017-05-12

    Polyamine conjugates with bicyclic terminal groups including quinazoline, naphthalene, quinoline, coumarine and indole have been obtained and their cytotoxic activity against PC-3, DU-145 and MCF-7 cell lines was evaluated in vitro. Their antiproliferative potential differed markedly and depended on both their chemical structure and the type of cancer cell line. Noncovalent DNA-binding properties of the most active compounds have been examined using ds-DNA thermal melting studies and topo I activity assay. The promising biological activity, DNA intercalative binding mode and favorable drug-like properties of bis(naphthalene-2-carboxamides) make them a good lead for further development of potential anticancer drugs.

  9. Ultrasonic-assisted synthesis and strepavidin conjugation of amino-magnetic nanoparticles

    International Nuclear Information System (INIS)

    Liu Li; Jiao Qinghua; Peng Cheng; He Shijiang; Wang Lihua

    2008-01-01

    MNPs are widely used in biotechnology, magnetic resonance imaging, catalysis and other areas. In this paper, we propose a simple, quick, inexpensive and efficient way to prepare amino-MNPs with sonication-assisted process. The amino-MNPs prepared by hydrolyzing TEOS and APS were characterized by SEM, TEM and FTIR. Conjugation of SA and amino-MNPs was also studied. The biotin bound capacity of prepared SA coated amino-MNPs was 1.824 nmol/mg, which well meet the need of biological application. (authors)

  10. Synthesis of Donor-Acceptor Conjugated Polymers by "CLICK" Polymerization for OPV applications

    DEFF Research Database (Denmark)

    Brandt, Rasmus Guldbæk; Yu, Donghong

    The intent of this study was to utilize the Copper(I)-catalyzed Azide Alkyne Cycloaddition (CuAAC) as a polymerization technique (“Click” Polymerization) for synthesizing novel π-conjugated low band gap polymers for organic photovoltaic applications (OPV). The chosen approach was to synthesize...... an alternating electron donating (donor, D) and electron withdrawing (acceptor, A) co-polymer. The chosen monomers were well known units, and the novelty lies in using the monomer units with the click methodology. An insoluble alternating copolymer consisting of 2,7-diazido-9,9-dioctyl-9Hflourene and 1...

  11. Nitrogen-Rich Conjugated Microporous Polymers: Facile Synthesis, Efficient Gas Storage, and Heterogeneous Catalysis.

    Science.gov (United States)

    Liao, Yaozu; Cheng, Zhonghua; Zuo, Weiwei; Thomas, Arne; Faul, Charl F J

    2017-11-08

    Nitrogen-rich conjugated microporous polymers (NCMPs) have attracted great attention in recent years owing to their polarity, basicity, and ability to coordinate metal ions. Herein, three NCMPs, structurally close to polyaniline, were facilely synthesized via chemical oxidative polymerization between multiconnected aniline precursors. The NCMPs with high N content (11.84 wt %), intrinsic ultramicroporosity (iodine vapor uptake at ambient pressure. Moreover, these NCMPs act as support for palladium catalysts and can maintain >94% activity in Suzuki-Miyaura coupling reactions after six continuous runs.

  12. Recent Developments in the Synthesis of Biomacromolecules and their Conjugates by Single Electron Transfer-Living Radical Polymerization.

    Science.gov (United States)

    Lligadas, Gerard; Grama, Silvia; Percec, Virgil

    2017-04-10

    Single electron transfer-living radical polymerization (SET-LRP) represents a robust and versatile tool for the synthesis of vinyl polymers with well-defined topology and chain end functionality. The crucial step in SET-LRP is the disproportionation of the Cu(I)X generated by activation with Cu(0) wire, powder, or nascent Cu(0) generated in situ into nascent, extremely reactive Cu(0) atoms and nanoparticles and Cu(II)X 2 . Nascent Cu(0) activates the initiator and dormant chains via a homogeneous or heterogeneous outer-sphere single-electron transfer mechanism (SET-LRP). SET-LRP provides an ultrafast polymerization of a plethora of monomers (e.g., (meth)-acrylates, (meth)-acrylamides, styrene, and vinyl chloride) including hydrophobic and water insoluble to hydrophilic and water soluble. Some advantageous features of SET-LRP are (i) the use of Cu(0) wire or powder as readily available catalysts under mild reaction conditions, (ii) their excellent control over molecular weight evolution and distribution as well as polymer chain ends, (iii) their high functional group tolerance allowing the polymerization of commercial-grade monomers, and (iv) the limited purification required for the resulting polymers. In this Perspective, we highlight the recent advancements of SET-LRP in the synthesis of biomacromolecules and of their conjugates.

  13. 6-Aminocoumarin-naphthoquinone conjugates: design, synthesis, photophysical and electrochemical properties and DFT calculations

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, Fabio S.; Ronconi, Celia M.; Sousa, Mikaelly O.B.; Silveira, Gleiciani Q.; Vargas, Maria D., E-mail: miranda@vm.uff.br, E-mail: mdvargascp@gmail.com [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Inst. de Quimica

    2014-01-15

    Four novel 6-aminocoumarin-naphthoquinone conjugates were synthesized and their photophysical and electrochemical properties, investigated. 2-Chloro-3-(2-oxo-2H-chromen-6- ylamino)-1,4-naphthoquinone 1 did not present appreciable fluorescence in solution in comparison with 6-aminocoumarin, 6-AC. In order to understand the reasons for the fluorescence quenching in this compound, two strategies were attempted. Firstly, compound 1 was N-methylated to remove the intramolecular N-H...O=C electrostatic interaction that maintained the two units fixed, but the emission properties of the product 2 were not significantly different from those of 1. Time-dependent density functional theory (TD-DFT) calculations of compounds 1 and 2 indicate that the fluorescence quenching is related to the electron acceptor character of the naphthoquinone ring. The second strategy, therefore, involved the substitution of the chlorine atom in position 2 of the naphthoquinone nucleus for different electron donor groups (compounds 3-5), but again the emission properties did not change significantly. To explain these experimental findings, TD-DFT calculations of the ground (S{sub 0}) and excited (S{sub 1}) states of all molecules in solution were carried out. The results suggest that the energy states in these conjugates are such that the fluorescent group (6-AC) donates electrons to the naphthoquinone LUMO resulting in an oxidative photoinduced electron transfer (oxidative-PET). (author)

  14. Improved synthesis of glycine, taurine and sulfate conjugated bile acids as reference compounds and internal standards for ESI-MS/MS urinary profiling of inborn errors of bile acid synthesis.

    Science.gov (United States)

    Donazzolo, Elena; Gucciardi, Antonina; Mazzier, Daniela; Peggion, Cristina; Pirillo, Paola; Naturale, Mauro; Moretto, Alessandro; Giordano, Giuseppe

    2017-04-01

    Bile acid synthesis defects are rare genetic disorders characterized by a failure to produce normal bile acids (BAs), and by an accumulation of unusual and intermediary cholanoids. Measurements of cholanoids in urine samples by mass spectrometry are a gold standard for the diagnosis of these diseases. In this work improved methods for the chemical synthesis of 30 BAs conjugated with glycine, taurine and sulfate were developed. Diethyl phosphorocyanidate (DEPC) and diphenyl phosphoryl azide (DPPA) were used as coupling reagents for glycine and taurine conjugation. Sulfated BAs were obtained by sulfur trioxide-triethylamine complex (SO 3 -TEA) as sulfating agent and thereafter conjugated with glycine and taurine. All products were characterized by NMR, IR spectroscopy and high resolution mass spectrometry (HRMS). The use of these compounds as internal standards allows an improved accuracy of both identification and quantification of urinary bile acids. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Synthesis and two-photon absorption property of new π-conjugated ...

    Indian Academy of Sciences (India)

    In this communication, we report the synthesis of three newly designed fluorescent polymers ... The new polymers, carrying donor and acceptor heterocyclic moieties with different spacer groups were found to be thermally stable and good of nonlinear optical (NLO) ..... ponds to the degradation of polymer backbone leaving.

  16. Synthesis and spectroscopic properties of porphyrin - (thia)calix[4]arene conjugates

    Czech Academy of Sciences Publication Activity Database

    Dudic, M.; Lhoták, P.; Stibor, I.; Dvořáková, H.; Lang, Kamil

    2002-01-01

    Roč. 58, - (2002), s. 5475-5482 ISSN 0040-4020 R&D Projects: GA ČR GA104/00/1722; GA ČR GA203/99/1163 Institutional research plan: CEZ:AV0Z4032918 Keywords : porphyrin * calix[4]arene * synthesis Subject RIV: CA - Inorganic Chemistry Impact factor: 2.420, year: 2002

  17. Coumarin–pyrene conjugate: Synthesis, structure and Cu-selective fluorescent sensing in mammalian kidney cells

    International Nuclear Information System (INIS)

    Wani, Manzoor Ahmad; Singh, Pankaj Kumar; Pandey, Rampal; Pandey, Mrituanjay D.

    2016-01-01

    In this work, we report a coumarin–pyrene based fluorescent probes (E)-7-(diethylamino)-3-((pyren-1-ylimino)methyl)-2H-chromen-2-one (1) and (E)-7-(diethylamino)-3-((pyren-1-ylmethylimino)methyl)-2H-chromen-2-one (2) for the selective detection of Cu 2+ ion. Receptor 1 upon binding with Cu 2+ exhibited substantial fluorescence quenching as a detection response. Probe 1 induces green fluorescence in a cell lines derived from monkey kidney tissue and subsequent quenching of fluorescence in these cells manifest that 1 can probably be used as a potential fluorescent sensor for the detection of Cu 2+ in biological samples too. However, 2 does not reveal any significant fluorescence change in presence of different metal ions. It is assumed that conjugation might be accountable for the discrete fluorescent behavior of 1 and 2.

  18. Receptor-mediated photo-cytotoxicity: synthesis of a photoactivatable psoralen derivative conjugated to insulin.

    Science.gov (United States)

    Gasparro, F P; Knobler, R M; Yemul, S S; Bisaccia, E; Edelson, R L

    1986-12-15

    4'-Aminomethyl-4,5',8-trimethylpsoralen has been chemically conjugated to insulin using a carbodiimide derivative. The psoralen moiety retains its photochemical reactivity as evidenced by its ability to crosslink DNA after exposure to long wavelength ultraviolet light (UVA, 320-400 nm). This chimeric molecule has been used to selectively kill a population of lymphocytes whose expression of insulin receptors has been stimulated with phytohemagglutinin. Insulin carries the psoralen into the cell via receptor-mediated endocytosis, where it is subsequently activated by exposure to UVA light. The UVA induced activity of AMT-insulin can be blocked by the presence of native insulin. The viability of unstimulated lymphocytes was not affected by AMT-insulin and UVA light. The hybrid insulin-psoralen molecule may be a prototype for a family of phototoxic drugs which can be selectively delivered to subsets of lymphocytes.

  19. A method for controlling the synthesis of stable twisted two-dimensional conjugated molecules

    Science.gov (United States)

    Li, Yongjun; Jia, Zhiyu; Xiao, Shengqiang; Liu, Huibiao; Li, Yuliang

    2016-01-01

    Thermodynamic stabilization (π-electron delocalization through effective conjugation) and kinetic stabilization (blocking the most-reactive sites) are important considerations when designing stable polycyclic aromatic hydrocarbons displaying tunable optoelectronic properties. Here, we demonstrate an efficient method for preparing a series of stable two-dimensional (2D) twisted dibenzoterrylene-acenes. We investigated their electronic structures and geometries in the ground state through various experiments assisted by calculations using density functional theory. We find that the length of the acene has a clear effect on the photophysical, electrochemical, and magnetic properties. These molecules exhibit tunable ground-state structures, in which a stable open-shell quintet tetraradical can be transferred to triplet diradicals. Such compounds are promising candidates for use in nonlinear optics, field effect transistors and organic spintronics; furthermore, they may enable broader applications of 2D small organic molecules in high-performance electronic and optical devices. PMID:27181692

  20. Synthesis, structure, antioxidant activity, and water solubility of trolox ion conjugates

    Directory of Open Access Journals (Sweden)

    Yuliya V. Yushkova

    2018-01-01

    Full Text Available The interaction of trolox with ammonia, alkylamines of different classes, and amino derivatives of heterocyclic compounds, including nitroxyl radicals and alkaloids, led to the production of ammonium salts called ion conjugates (ICs. Five ICs were characterised by X-ray diffraction. This is the first time a wide range of ICs were made from trolox with amines, and ESI-MS data demonstrated they have the potential to generate pseudomolecular [(A−B+ + H]+ ions. For all obtained trolox ICs, a significant increase (1–3 orders of magnitude in water solubility was achieved while retaining high antioxidant activity. ICs synthesised from two biologically active fragments may be used to create polyfunctional agents with varying solubility and bioavailability.

  1. Facile Synthesis and Cytotoxic Activity of the First Ferrocene-Resveratrol Conjugate

    Directory of Open Access Journals (Sweden)

    Veronika Kovač

    2016-09-01

    Full Text Available The bioorganometallic III containing trimethylene chain between ferrocene and resveratrol (3,5,4'-trihydroxystilbene, RSV moieties connected via ester bond has been synthesized. The novel bioconjugate was characterized using IR and NMR (1H, 13C, COSY, NOESY, HMBC spectroscopy, ESI-MS and HRMS. The RSV and ferrocene-RSV conjugate III were screened in vitro for their inhibitory effects against proliferation of hepatoblastoma (Hep G2 cells by MTT assay. Also, possible cytotoxicity towards normal ovary cells (CHO-K1 was evaluated. The obtained data revealed profound effects in biological/cytotoxic activity of III vs. RSV in Hep G2 cell line. Lower cytotoxicity of III was observed in normal ovary cells as compared to hepatoblastoma cells. This work is licensed under a Creative Commons Attribution 4.0 International License.

  2. Vitexin inhibits polyubiquitin synthesis by the ubiquitin-conjugating enzyme E2-25K.

    Science.gov (United States)

    Helms, Kimberli M; Wilson, Randall C; Ogungbe, Ifedayo V; Setzer, William N; Twigg, Pamela D

    2011-10-01

    An extract of bark from the tropical rainforest plant Byrsonima crassifolia was screened for inhibition of diubiquitin formation by the human ubiquitin-conjugating enzyme E2-25K. Activity assays with both the full-length enzyme and a truncated, active catalytic UBC domain revealed that the extract contained inhibitory properties. Separation of the extract into individual components and additional screens identified vitexin as the active inhibitor. An IC50 for vitexin was calculated to be approximately 0.5 mM. Molecular modeling simulations were used to predict the mode of inhibition and NMR spectra were used to confirm the binding site of vitexin to E2-25K.

  3. Conjugates of 1'-Aminoferrocene-1-carboxylic Acid and Proline: Synthesis, Conformational Analysis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Monika Kovačević

    2014-08-01

    Full Text Available Our previous studies showed that alteration of dipeptides Y-Fca-Ala-OMe (III into Y-Ala-Fca-OMe (IV (Y = Ac, Boc; Fca = 1'-aminoferrocene-1-carboxylic acid significantly influenced their conformational space. The novel bioconjugates Y-Fca-Pro-OMe (1, Y = Ac; 2, Y = Boc and Y-Pro-Fca-OMe (3, Y = Boc; 4, Y = Ac have been prepared in order to investigate the influence of proline, a well-known turn-inducer, on the conformational properties of small organometallic peptides with an exchanged constituent amino acid sequences. For this purpose, peptides 1–4 were subjected to detailed spectroscopic analysis (IR, NMR, CD spectroscopy in solution. The conformation of peptide 3 in the solid state was determined. Furthermore, the ability of the prepared conjugates to inhibit the growth of estrogen receptor-responsive MCF-7 mammary carcinoma cells and HeLa cervical carcinoma cells was tested.

  4. Synthesis and Characterization of Bovine Serum Albumin-Conjugated Copper Sulfide Nanocomposites

    Directory of Open Access Journals (Sweden)

    Peng Huang

    2010-01-01

    Full Text Available A simple biomolecule-assisted solution route was developed to synthesize Bovine Serum Albumin-conjugated copper sulfide (CuS/BSA nanocomposites, directly using copper salts and thioacetamide (TAA as the starting materials with a zwitterionic surfactant Bovine Serum Albumin (BSA as foaming and stabilizing agent. The CuS/BSA nanocomposites have been characterized by UV, TEM, Zeta, DLS, XRD, and FTIR. The results indicate that the as-prepared CuS/BSA nanocomposites are approximate sphere with a size distribution from 10 to 35 nm in diameter and good dispersibility, depending highly on concentration of BSA concentration. These protein-assisted synthesized nanocomposites have a great potential application in biomedical engineering and microelectronics.

  5. Donor-Acceptor Conjugated Macrocycles: Synthesis and Host-Guest Coassembly with Fullerene toward Photovoltaic Application.

    Science.gov (United States)

    Zhang, Si-Qi; Liu, Zhen-Yu; Fu, Wei-Fei; Liu, Feng; Wang, Chuan-Ming; Sheng, Chun-Qi; Wang, Yi-Fei; Deng, Ke; Zeng, Qing-Dao; Shu, Li-Jin; Wan, Jun-Hua; Chen, Hong-Zheng; Russell, Thomas P

    2017-11-28

    Electron-rich (donor) and electron-deficient (acceptor) units to construct donor-acceptor (D-A) conjugated macrocycles were investigated to elucidate their interactions with electron-deficient fullerene. Triphenylamine and 4,7-bisthienyl-2,1,3-benzothiadiazole were alternately linked through acetylene, as the donor and acceptor units, respectively, for pentagonal 3B2A and hexagonal 4B2A macrocycles. As detected by scanning tunneling microscopy, both D-A macrocycles were found to form an interesting concentration-controlled nanoporous monolayer on highly oriented pyrolytic graphite, which could effectively capture fullerene. Significantly, the fullerene filling was cavity-size-dependent with only one C 70 or PC 71 BM molecule accommodated by 3B2A, while two were accommodated by 4B2A. Density functional theory calculations were also utilized to gain insight into the host-guest systems and indicted that the S···π contact is responsible for stabilizing these host-guest systems. Owing to the ellipsoidal shape of C 70 , C 70 molecules are standing or lying in molecular cavities depending on the energy optimization. For the 3B2A/PC 71 BM blended film, PC 71 BM was intercalated into the cavity formed by the macrocycle 3B2A and provided excellent power conversion efficiency despite the broad band gap (2.1 eV) of 3B2A. This study of D-A macrocycles incorporating fullerene provides insights into the interaction mechanism and electronic structure in the host-guest complexes. More importantly, this is a representative example using D-A macrocycles as a donor to match with the spherical fullerene acceptor for photovoltaic applications, which offer a good approach to achieve molecular scale p-n junctions for substantially enhanced efficiencies of organic solar cells through replacing linear polymer donors by cyclic conjugated oligomers.

  6. Prazosin-Conjugated Matrices Based on Biodegradable Polymers and α-Amino Acids--Synthesis, Characterization, and in Vitro Release Study.

    Science.gov (United States)

    Oledzka, Ewa; Sawicka, Anna; Sobczak, Marcin; Nalecz-Jawecki, Grzegorz; Skrzypczak, Agata; Kolodziejski, Waclaw

    2015-08-12

    Novel and promising macromolecular conjugates of the α1-adrenergic blocker prazosin were directly synthesized by covalent incorporation of the drug to matrices composed of biodegradable polymers and α-amino acids for the development of a polymeric implantable drug delivery carrier. The cyto- and genotoxicity of the synthesized matrices were evaluated using a bacterial luminescence test, protozoan assay, and Salmonella typhimurium TA1535. A new urethane bond was formed between the hydroxyl end-groups of the synthesized polymer matrices and an amine group of prazosin, using 1,1'-carbonyldiimidazole (CDI) as a coupling agent. The structure of the polymeric conjugates was characterized by various spectroscopy techniques. A study of hydrogen nuclear magnetic resonance ((1)H-NMR) and differential scanning calorimetry (DSC) thermodiagrams indicated that the presence of prazosin pendant groups in the macromolecule structures increased the polymer's rigidity alongside increasing glass transition temperature. It has been found that the kinetic release of prazosin from the obtained macromolecular conjugates, tested in vitro under different conditions, is strongly dependent on the physicochemical properties of polymeric matrices. Furthermore, the presence of a urethane bond in the macromolecular conjugates allowed for obtaining a relatively controlled release profile of the drug. The obtained results confirm that the pharmacokinetics of prazosin might be improved through the synthesis of polymeric conjugates containing biomedical polymers and α-amino acids in the macromolecule.

  7. A Stepwise Approach for the Synthesis of Folic Acid Conjugates with Protein Kinase Inhibitors

    Czech Academy of Sciences Publication Activity Database

    Krajčovičová, S.; Gucký, Tomáš; Hendrychová, Denisa; Kryštof, Vladimír; Soural, M.

    2017-01-01

    Roč. 82, č. 24 (2017), s. 13530-13541 ISSN 0022-3263 R&D Projects: GA ČR(CZ) GA15-15264S; GA MŠk(CZ) LO1304 Institutional support: RVO:61389030 Keywords : CYCLIN-DEPENDENT KINASES * FOLATE RECEPTOR * REGIOSELECTIVE SYNTHESIS Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Organic chemistry Impact factor: 4.849, year: 2016

  8. An efficient synthesis of tetramic acid derivatives with extended conjugation from L-Ascorbic Acid

    Directory of Open Access Journals (Sweden)

    Bisht Surendra S

    2006-12-01

    Full Text Available Abstract Background Tetramic acids with polyenyl substituents are an important class of compounds in medicinal chemistry. Both solid and solution phase syntheses of such molecules have been reported recently. Thiolactomycin, a clinical candidate for treatment of tuberculosis has led to further explorations in this class. We have recently developed an efficient synthesis of tetramic acids derivatives from L- ascorbic acid. In continuation of this work, we have synthesised dienyl tetramic acid derivatives. Results 5,6-O-Isopropylidene-ascorbic acid on reaction with DBU led to the formation of tetronolactonyl allyl alcohol, which on oxidation with pyridinium chlorochromate gave the respective tetranolactonyl allylic aldehydes. Wittig olefination followed by reaction of the resulting tetranolactonyl dienyl esters with different amines resulted in the respective 5-hydroxy lactams. Subsequent dehydration of the hydroxy lactams with p-toluene sulphonic acid afforded the dienyl tetramic acid derivatives. All reactions were performed at ambient temperature and the yields are good. Conclusion An efficient and practical method for the synthesis of dienyl tetramic acid derivatives from inexpensive and easily accessible ascorbic acid has been developed. The compounds bear structural similarities to the tetramic acid based polyenic antibiotics and thus this method offers a new and short route for the synthesis of tetramic acid derivatives of biological significance.

  9. Synthesis of a Cholesteryl-HEG Phosphoramidite Derivative and Its Application to Lipid-conjugates of the Anti-HIV 5'TGGGAG3' Hotoda’s Sequence

    Directory of Open Access Journals (Sweden)

    Domenica Musumeci

    2012-10-01

    Full Text Available A novel phosphoramidite derivative of cholesterol, with an ether-linked hexaethylene glycol (HEG spacer arm, has been obtained through simple and reproducible solid phase modified oligonucleotide synthesis manipulations. This building block and the known phosphoramidite derivative of 3b-(2-hydroxyethoxycholesterol have been exploited in standard oligonucleotide synthesis protocols for the preparation of 5'- conjugates of the G-quadruplex-forming 5'TGGGAG3' oligomer, known as the Hotoda’s sequence, to produce new potential anti-HIV agents.

  10. Organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin on chalcones: Synthesis, NMR and single-crystal X-ray diffraction studies of novel warfarin analogues

    Science.gov (United States)

    Talhi, Oualid; Fernandes, José A.; Pinto, Diana C. G. A.; Almeida Paz, Filipe A.; Silva, Artur M. S.

    2015-08-01

    The synthesis of a new series of warfarin analogues by convenient organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin to chalcone derivatives is described. 1H NMR spectroscopy evidenced the presence of a predominant acyclic open-form together with the cyclic hemiketal tautomers of the resulting Michael adducts. The acyclic open-form has been unequivocally proved by single-crystal X-ray diffraction analysis. The use of the B ring ortho-hydroxychalcone synthons in this reaction has led to a diastereoselective synthesis of warfarin bicyclo[3.3.1]nonane ketal derivatives.

  11. Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp2–H bond arylations

    Directory of Open Access Journals (Sweden)

    Fatiha Abdelmalek

    2015-10-01

    Full Text Available We report herein a two or three step synthesis of fluorinated π-conjugated oligomers through iterative C–H bond arylations. Palladium-catalyzed desulfitative arylation of heteroarenes allowed in a first step the synthesis of fluoroaryl-heteroarene units in high yields. Then, the next steps involve direct arylation with aryl bromides catalyzed by PdCl(C3H5(dppb to afford triad or tetrad heteroaromatic compounds via regioselective activation of C(sp2–H bonds.

  12. Synthesis and evaluation of 99mTc/99Tc-MAG3-biotin conjugates for antibody pretargeting strategies

    International Nuclear Information System (INIS)

    Gog, Frank B. van; Visser, Gerard W.M.; Gowrising, Radjish W.A.; Snow, Gordon B.; Dongen, Guus A.M.S. van

    1998-01-01

    Four 99m Tc-MAG3-biotin conjugates were synthesized to determine their potential use in antibody pretargeting strategies for radioimmunoscintigraphy (RIS). To use these 99m Tc-MAG3-biotin conjugates as model compounds for 186 Re-MAG3-biotin conjugates for radioimmunotherapy (RIT), nanomolar amounts of 99 Tc were added as carrier to 99m Tc. The biotin derivatives used for the preparation of the conjugates - biocytin, biotin hydrazide, biotinyl-piperazine, and biotinyl-diaminosuccinic acid - differed at the site that is regarded to be susceptible to hydrolysis by biotinidase present in human plasma. All four conjugates were produced with high radiochemical purity, were stable in PBS, and demonstrated full binding capacity to streptavidin. The 99m Tc/ 99 Tc-MAG3-labeled biotinyl-piperazine and biotinyl-diaminosuccinic acid conjugates were stable in mouse as well as human plasma, whereas the corresponding biocytin and biotin hydrazide conjugates were rapidly degraded. The biodistribution in nude mice at 30 min after injection was similar for all conjugates, and a rapid blood clearance and high intestinal excretion were both observed. It is concluded that the metabolic routing of a conjugate containing biotin and MAG3 is dominated by these two moieties. For this reason, MAG3-biotin conjugates do not seem suited for pretargeted RIT, for which quantitative and fast renal excretion is a prerequisite to minimize radiation toxicity. However, in a pretargeted RIS approach the 99m Tc-MAG3-biotin conjugates might have potential

  13. Asymmetrically Substituted and π-Conjugated 2,2'-Bipyridine Derivatives: Synthesis, Spectroscopy, Computation, and Crystallography.

    Science.gov (United States)

    Bodapati, Ramakrishna; Sarma, Monima; Kanakati, Arunkumar; Das, Samar K

    2015-12-18

    A new series of monosubstituted styryl- and bistyryl-2,2'-bipyridine luminophores (compounds 16-23) have been synthesized via Horner-Wadsworth-Emmons reaction involving a monophosphonate and donor aromatic aldehydes. In the title chromophores, the amino donors are varied between acyclic and cyclic while the alkoxy donors are varied in terms of their number and position. The absorption maxima of these chromophores shift predominantly due to intramolecular charge transfer (ICT) between different donor and acceptor moieties. The title donor-acceptor molecules exhibit intense fluorescence in solution at room temperature, and their emissive behavior has been found to be highly sensitive to solvent polarity. The fluorescence spectra and quantum yields of all the chromophores were recorded in four different solvent media, and the chromophores 16, 17, 19, and 21 exhibit fluorescence in the solid state too. The influence of the nature and position of the donor functionalities in the conjugated backbone of the bipyridine moiety on the electronic absorption properties of the title chromophores (16-23) has been demonstrated, which has further been corroborated by DFT and TD-DFT computation both in gas phase and in solution phase. The crystal structure of compound 18 has been described as a representative member of the family (16-23).

  14. Synthesis, Characterization, and Retinol Stabilization of Fatty Amide-β-cyclodextrin Conjugates

    Directory of Open Access Journals (Sweden)

    Hwanhee Kim

    2016-07-01

    Full Text Available Amphiphilic cyclodextrin (CD has been the object of growing scientific attention because of its two recognition sites, the cavity and the apolar heart, formed by self-assembly. In the present study, mono[6-deoxy-6-(octadecanamido]-β-CD and mono[6-deoxy-6-(octadecenamido]-β-CD were successfully synthesized by reacting mono-6-amino-6-deoxy-β-CD with N-hydroxysuccinimide esters of corresponding fatty acids in DMF. The structures were analyzed using nuclear magnetic resonance spectroscopy and mass spectrometry. The amphiphilic β-CDs were able to form self-assembled nano-vesicles in water, and the supramolecular architectures were characterized using fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. Using the cavity-type nano-vesicles, all-trans-retinol was efficiently encapsulated; it was then stabilized against the photo-degradation. Therefore, the present fatty amide-β-CD conjugate will be a potential molecule for carrier systems in cosmetic and pharmaceutical applications.

  15. Synthesis of mesoporous silica nanoparticle-oxaliplatin conjugates for improved anticancer drug delivery.

    Science.gov (United States)

    He, Hongyan; Xiao, Haihua; Kuang, Huihui; Xie, Zhigang; Chen, Xuesi; Jing, Xiabin; Huang, Yubin

    2014-05-01

    Mesoporous silica nanoparticles (MSN) with 1,2-bidentate carboxyl groups on the surface reacted with 1,2-diaminecyclohexano platinum(II) dinitrate (DACH-Pt-(NO3)2) which is an active anticancer species of clinic relevant oxaliplatin to form MSN-Pt. The modification of the parent particles was monitored by (13)C, (29)Si solid-state NMR, X-ray measurements (XRD) and Fourier transform infrared spectroscopy (FT-IR). After loading with platinum drugs, MSN-Pt exhibited two strong Pt4f signals as indicated by X-ray photoelectron spectroscopy (XPS). The platinum content in the conjugates was calculated to be 9.7% according to ICP-MS measurements. Confocal laser scanning microscopy (CLSM) displayed that MSN-Pt were uptaken fast by HepG-2 cells and concentrated within endosomes and lysosomes. In vitro MTT assay of MSN-Pt demonstrated an improved cytotoxicity against HepG-2 cells than that of free oxaliplatin. This is due to the fact that MSN-Pt expressed higher platinum intracellular uptake and more DNA binding (Pt-DNA adducts) than free oxaliplatin. Hence this work highlighted that the platinum loaded MSN nanoparticles could be a promising future intelligent drug delivery system. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. De novo synthesis of trans-10, cis-12 conjugated linoleic acid in oleaginous yeast Yarrowia Lipolytica

    Directory of Open Access Journals (Sweden)

    Zhang Baixi

    2012-07-01

    Full Text Available Abstract Background Conjugated linoleic acid (CLA has many well-documented beneficial physiological effects. Due to the insufficient natural supply of CLA and low specificity of chemically produced CLA, an effective and isomer-specific production process is required for medicinal and nutritional purposes. Results The linoleic acid isomerase gene from Propionibacterium acnes was expressed in Yarrowia lipolytica Polh. Codon usage optimization of the PAI and multi-copy integration significantly improved the expression level of PAI in Y. lipolytica. The percentage of trans-10, cis-12 CLA was six times higher in yeast carrying the codon-optimized gene than in yeast carrying the native gene. In combination with multi-copy integration, the production yield was raised to approximately 30-fold. The amount of trans-10, cis-12 CLA reached 5.9% of total fatty acid yield in transformed Y. lipolytica. Conclusions This is the first report of production of trans-10, cis-12 CLA by the oleaginous yeast Y. lipolytica, using glucose as the sole carbon source through expression of linoleic acid isomerase from Propionibacterium acnes.

  17. De novo synthesis of trans-10, cis-12 conjugated linoleic acid in oleaginous yeast Yarrowia Lipolytica

    Science.gov (United States)

    2012-01-01

    Background Conjugated linoleic acid (CLA) has many well-documented beneficial physiological effects. Due to the insufficient natural supply of CLA and low specificity of chemically produced CLA, an effective and isomer-specific production process is required for medicinal and nutritional purposes. Results The linoleic acid isomerase gene from Propionibacterium acnes was expressed in Yarrowia lipolytica Polh. Codon usage optimization of the PAI and multi-copy integration significantly improved the expression level of PAI in Y. lipolytica. The percentage of trans-10, cis-12 CLA was six times higher in yeast carrying the codon-optimized gene than in yeast carrying the native gene. In combination with multi-copy integration, the production yield was raised to approximately 30-fold. The amount of trans-10, cis-12 CLA reached 5.9% of total fatty acid yield in transformed Y. lipolytica. Conclusions This is the first report of production of trans-10, cis-12 CLA by the oleaginous yeast Y. lipolytica, using glucose as the sole carbon source through expression of linoleic acid isomerase from Propionibacterium acnes. PMID:22545818

  18. Synthesis of Symmetrical Tetrameric Conjugates of the Radiolanthanide Chelator DOTPI for Application in Endoradiotherapy by Means of Click Chemistry

    Directory of Open Access Journals (Sweden)

    Alexander Wurzer

    2018-04-01

    Full Text Available Due to its 4 carbonic acid groups being available for bioconjugation, the cyclen tetraphosphinate chelator DOTPI, 1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetrakis[methylene(2-carboxyethylphosphinic acid], represents an ideal scaffold for synthesis of tetrameric bioconjugates for labeling with radiolanthanides, to be applied as endoradiotherapeuticals. We optimized a protocol for bio-orthogonal DOTPI conjugation via Cu(I-catalyzed Huisgen-cycloaddition of terminal azides and alkynes (CuAAC, based on the building block DOTPI(azide4. A detailed investigation of kinetic properties of Cu(II-DOTPI complexes aimed at optimization of removal of DOTPI-bound copper by transchelation. Protonation and equilibrium properties of Ca(II-, Zn(II, and Cu(II-complexes of DOTPI and its tetra-cyclohexylamide DOTPI(Chx4 (a model for DOTPI conjugates as well as kinetic inertness (transchelation challenge in the presence of 20 to 40-fold excess of EDTA were investigated by pH-potentiometry and spectrophotometry. Similar stability constants of CaII-, ZnII, and CuII-complexes of DOTPI (logK(CaL = 8.65, logK(ZnL = 15.40, logK(CuL = 20.30 and DOTPI(Chx4 (logK(CaL = 8.99, logK(ZnL = 15.13, logK(CuL = 20.42 were found. Transchelation of Cu(II-complexes occurs via proton-assisted dissociation, whereafter released Cu(II is scavenged by EDTA. The corresponding dissociation rates [kd = 25 × 10−7 and 5 × 10−7 s−1 for Cu(DOTPI and Cu(DOTPI(Chx4, respectively, at pH 4 and 298 K] indicate that conjugation increases the kinetic inertness by a factor of 5. However, demetallation is completed within 4.5 and 7.2 h at pH 2 and 25°C, respectively, indicating that Cu(II removal after formation of CuAAC can be achieved in an uncomplicated manner by addition of excess H4EDTA. For proof-of-principle, tetrameric DOTPI conjugates of the prostate-specific membrane antigen (PSMA targeting motif Lys-urea-Glu (KuE were synthesized via CuAAC as well as dibenzo-azacyclooctine (DBCO based

  19. Synthesis of symmetrical tetrameric conjugates of the radiolanthanide chelator DOTPI for application in endoradiotherapy by means of click chemistry

    Science.gov (United States)

    Wurzer, Alexander; Vágner, Adrienn; Horváth, Dávid; Fellegi, Flóra; Wester, Hans-Jürgen; Kálmán, Ferenc K.; Notni, Johannes

    2018-04-01

    Due to its 4 carbonic acid groups being available for bioconjugation, the cyclen tetraphosphinate chelator DOTPI, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis[methylene(2-carboxyethylphosphinic acid)], represents an ideal scaffold for synthesis of tetrameric bioconjugates for labeling with radiolanthanides, to be applied as endoradiotherapeuticals. We optimized a protocol for bio-orthogonal DOTPI conjugation via Cu(I)-catalyzed Huisgen-cycloaddition of terminal azides and alkynes (CuAAC), based on the building block DOTPI(azide)4. A detailed investigation of kinetic properties of Cu(II)-DOTPI complexes aimed at optimization of removal of DOTPI-bound copper by transchelation. Protonation and equilibrium properties of Ca(II)-, Zn(II) and Cu(II)-complexes of DOTPI and its tetra-cyclohexylamide DOTPI(Chx)4 (a model for DOTPI conjugates) as well as kinetic inertness (transchelation challenge in the presence of 20 to 40-fold excess of EDTA) were investigated by pH-potentiometry and spectrophotometry. Similar stability constants of CaII-, ZnII and CuII-complexes of DOTPI (logK(CaL)=8.65, logK(ZnL=15.40, logK(CuL)=20.30) and DOTPI(Chx)4 (logK(CaL)=8.99, logK(ZnL)=15.13, logK(CuL)=20.42) were found. Transchelation of CuII-complexes occurs via proton-assisted dissociation, whereafter released Cu(II) is scavenged by EDTA. The corresponding dissociation rates (kd=25×10‑7 and 5×10‑7 s‑1 for Cu(DOTPI) and Cu(DOTPI(Chx)4), respectively, at pH 4 and 298 K) indicate that conjugation increases the kinetic inertness by a factor of 5. However demetallation is completed within 4.5 and 7.2 hours at pH 2 and 25 °C, respectively, indicating that CuII removal after formation of CuAAC can be achieved in an uncomplicated manner by addition of excess H4EDTA. For proof-of-principle, tetrameric DOTPI conjugates of the prostate-specific membrane antigen (PSMA) targeting motif Lys-urea-Glu (KuE) were synthesized via CuAAC as well as dibenzo-cyclooctine (DBCO) based, strain

  20. Synthesis of upconversion nanoparticles conjugated with graphene oxide quantum dots and their use against cancer cell imaging and photodynamic therapy.

    Science.gov (United States)

    Choi, Seung Yoo; Baek, Seung Hoon; Chang, Sung-Jin; Song, Yohan; Rafique, Rafia; Lee, Kang Taek; Park, Tae Jung

    2017-07-15

    Multifunctional nanocomposite has a huge potential for cell imaging, drug delivery, and improving therapeutic effect with less side effects. To date, diverse approaches have been demonstrated to endow a single nanostructure with multifunctionality. Herein, we report the synthesis and application of core-shell nanoparticles composed with upconversion nanoparticle (UCNP) as a core and a graphene oxide quantum dot (GOQD) as a shell. The UCNP was prepared and applied for imaging-guided analyses of upconversion luminescence. GOQD was prepared and employed as promising drug delivery vehicles to improve anti-tumor therapy effect in this study. Unique properties of UCNPs and GOQDs were incorporated into a single nanostructure to provide desirable functions for cell imaging and drug delivery. In addition, hypocrellin A (HA) was loaded on GOQDs for photo-dynamic therapy (PDT). HA, a commonly used chemotherapy drug and a photo-sensitizer, was conjugated with GOQD by π-π interaction and loaded on PEGylated UCNP without complicated synthetic process, which can break structure of HA. Applying these core-shell nanoparticles to MTT assay, we demonstrated that the UCNPs with GOQD shell loaded with HA could be excellent candidates as multifunctional agents for cell imaging, drug delivery and cell therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Synthesis and characterization of folate decorated albumin bio-conjugate nanoparticles loaded with a synthetic curcumin difluorinated analogue.

    Science.gov (United States)

    Gawde, Kaustubh A; Kesharwani, Prashant; Sau, Samaresh; Sarkar, Fazlul H; Padhye, Subhash; Kashaw, Sushil K; Iyer, Arun K

    2017-06-15

    Albumin-bound paclitaxel colloidal nanoparticle (Abraxane®) is an FDA approved anticancer formulation available in the market. It is a suspension which is currently used therapeutically for treating cancers of the breast, lung, and pancreas among others. CDF is a novel new and potent synthetic curcumin analogue that is widely used for breast and ovarian cancer. The aim of this study was to use biocompatible albumin as well as folate decorated albumin to formulate colloidal nanoparticles encapsulating curcumin difluorinated (CDF). CDF has demonstrated a 16-fold improvement in stability and remarkable anticancer potency compared to its natural derivative, curcumin. CDF showed marked inhibition of cancer cell growth through down-regulation of multiple miRNAs, up-regulation of phosphatase and tensin homolog (PTEN), and attenuation of histone methyl transferase EZH2. However, CDF is highly hydrophobic and photodegradable with sparing aqueous solubility. In this study, we have formulated albumin nanoparticle using a modified desolvation method, which yielded high CDF loading in a nanoformulation. The physicochemical properties of CDF loaded albumin and folate-decorated albumin nanosuspensions were assessed for particle size, morphology, zeta potential, drug encapsulation efficiency/loading, solubility and drug release. Importantly, the folate ligand decorated albumin nanoparticles were formulated in principle to passively and actively target folate-overexpressing-cancers. In this study, the synthesis and optimization of BSA and folate decorated BSA conjugated CDF nanoparticles are assessed in detail that will be useful for its future clinical translation. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation.

    Science.gov (United States)

    Scrivano, Luca; Iacopetta, Domenico; Sinicropi, Maria Stefania; Saturnino, Carmela; Longo, Pasquale; Parisi, Ortensia Ilaria; Puoci, Francesco

    2017-11-01

    Sericin is a natural protein that has been used in biomedical and pharmaceutical fields as raw material for polypeptide-based drug delivery systems (DDSs). In this paper, it has been employed as pharmaceutical biopolymer for the production of sunitinib-polypeptide conjugate. The synthesis has been carried out by simple click reaction in water, using the redox couple l-ascorbic acid/hydrogen peroxide as a free radical grafting initiator. The bioconjugate molecular weight (50 kDa < Mw < 75 kDa) was obtained by SDS-PAGE, while the spectroscopic characteristics have been studied in order to reveal the presence of grafted sunitinib. In both FT-IR and UV/Vis spectra, signals corresponding to sunitinib functional groups have been identified. Since sunitinib is an anticancer drug characterized by low bioavailability and low permeability, the bioconjugation aimed at their enhancement. In vitro studies demonstrated that bioavailability has been increased to almost 74%, compared with commercial formulation. Also cell membrane permeability has been augmented in in vitro tests, in which membrane models have been used to determine the lipid membrane/physiological fluid partition coefficient (Kp). The log(Kp) value of the bioconjugate was increased to over 4. This effect resulted in a three-fold decrease of IC 50 value against MCF-7 cells.

  3. Thermocleavable π‐Conjugated Polymers – Synthesis and photovoltaic applications

    DEFF Research Database (Denmark)

    Petersen, Martin Helgesen

    Polymer solar cells (plastic solar cells) have seen remarkable improvements in recent years where power conversion efficiencies of up to 6% have been reported for small area devices. However in terms of stability polymer solar cells degrade during illumination and in the dark leading to operational...... (>20000 hours). This Ph.D. thesis describes the synthesis, characterization and photovoltaic applications of these novel polymer materials. A key feature of these materials is that solubilizing thermocleavable alkyl ester side chains are introduced on the polymer backbone. The side chains make the polymer...

  4. SYNTHESIS OF 25-HYDROXYVITAMIN D3 CONJUGATE WITH KEYHOLE LIMPET HEMOCYANIN AND OBTAINING OF IMMUNE SERA

    Directory of Open Access Journals (Sweden)

    А. O. Mazanova

    2015-08-01

    Full Text Available The study was aimed at obtaining polyclonal antibodies that recognize 25-Hydroxyvitamin D3, for their further specifications and applications in immunochemical test systems of 25-Hydroxyvitamin D3, determination in blood serum. We used the methods of chemical synthesis of immunoconjugates (modified carbodiimide method using N´-ethyl carbodiimide, thin layer chromatography, gel filtration and indirect immunoenzyme analysis ELISA. The work describes the stages of the synthesis of 25-Hydroxyvitamin D3, immunoconjugate with keyhole limpet hemocyanin (KLH, which was used for receiving immune sera. As a result of mouse and rabbit immunization antisera were obtained and antibody titers against 25-Hydroxyvitamin D3, were tested by immunoenzyme assay. It was demonstrated that the titer of specific antibodies was higher in rabbits compared with mice. The resulting polyclonal antibodies can be used for the development of immunochemical test systems for screening studies of 25-Hydroxyvitamin D3, content in human blood serum as a marker of vitamin D3 availability.

  5. Conjugated fatty acid synthesis: residues 111 and 115 influence product partitioning of Momordica charantia conjugase.

    Science.gov (United States)

    Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

    2012-05-11

    Conjugated linolenic acids (CLNs), 18:3 Δ(9,11,13), lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ(9,12,15)). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ(9cis,11trans,13cis)) or α-eleostearic acid (18:3 Δ(9cis,11trans,13trans)). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation.

  6. Enzymatic Synthesis of Extremely Pure Triacylglycerols Enriched in Conjugated Linoleic Acids

    Directory of Open Access Journals (Sweden)

    Bo Yang

    2013-08-01

    Full Text Available This work was objectively targeted to synthesize extremely pure triacylglycerols (TAG enriched in conjugated linoleic acids (CLAs for medical and dietetic purposes. Extremely pure CLA-enriched TAG was successfully synthesized by using the multi-step process: TAG was primarily synthesized by lipase-catalyzed esterification of CLA and glycerol and then the lower glycerides [monoacylglycerol (MAG and diacylglycerol (DAG] in the esterification mixtures was hydrolyzed to free fatty acids (FFAs by a mono- and di-acylglycerol lipase (lipase SMG1, finally, the FFAs were further separated from TAG by low temperature (150 °C molecular distillation. The operation parameters for the lipase SMG1-catalyzed hydrolysis were optimized using response surface methodology based on the central composite rotatable design (CCRD. The operation parameters included water content, pH and reaction temperature and all of these three parameters showed significant effects on the hydrolysis of lower glycerides. The optimal conditions were obtained with a water content of 66.4% (w/w, with respect to oil mass, pH at 5.7 and 1 h of reaction time at 19.6 °C. Under these conditions, the content of lower glycerides in the reaction mixture decreased from 45.2% to 0.3% and the purity of CLA-enriched TAG reached 99.7%. Further purification of TAG was accomplished by molecular distillation and the final CLA-enriched TAG product yielded 99.8% of TAG. These extremely pure CLA-enriched TAG would be used for in vivo studies in animals and humans in order to get specific information concerning CLA metabolism.

  7. Polycationic nanoparticles: (1) synthesis of a polylysine-MION conjugate and its application in labeling fibroblasts.

    Science.gov (United States)

    Groman, Ernest V; Yang, Meiheng; Reinhardt, Christopher P; Weinberg, James S; Vaccaro, Dennis E

    2009-03-01

    Nanoparticles are increasingly used to label cells to track them by imaging or to quantify them in vivo. However, normal cellular uptake mechanisms are inadequate to load cells with tracking label. We propose a simple method to coat nanoparticles, such as monocrystalline iron oxide nanoparticle (MION), with the transfection agent polylysine in order to facilitate rapid, uniform, and heavy labeling of fibroblasts. The method is based on commercially available reagents, requires no more than 1 h of laboratory contact time, and can be accomplished safely without a chemical hood. A suspension of MION was treated by addition of solid sodium periodate to oxidize glucose residues of dextran and introduced aldehyde groups to the dextran coat surrounding MION's crystalline magnetite core. After a 30-min incubation to effect oxidation, unreacted periodate was quenched with glycerol. The preparation was dialyzed to remove reactants and diluted to a final concentration of 2 mg Fe/ml. Poly-L-lysine was added to the oxidized MION (MION-A) to form reversible covalent Schiff base linkages. The resulting conjugate, a polylysine iron oxide nano-particle is abbreviated PLION. NIH3T3 fibroblasts labeled with either MION, MION-A, or MION plus polylysine showed minimal uptake of iron while cells labeled with PLION acquired a brown hue demonstrating strong labeling with iron. Microscopic assessment of iron labeling was confirmed using Prussian blue staining. In some cells, the concentration of iron was sufficiently high and localized to suggest association with cytoplasmic vacuoles. The nucleus of the cell was not labeled. Cell labeling increased when the ratio of polylysine to MION increased and with increasing amount of PLION.

  8. Fluorinated arene, imide and unsaturated pyrrolidinone based donor acceptor conjugated polymers: Synthesis, structure-property and device studies

    Science.gov (United States)

    Liyanage, Arawwawala Don Thilanga

    After the discovery of doped polyacetylene, organic semiconductor materials are widely studied as high impending active components in consumer electronics. They have received substantial consideration due to their potential for structural tailoring, low cost, large area and mechanically flexible alternatives to common inorganic semiconductors. To acquire maximum use of these materials, it is essential to get a strong idea about their chemical and physical nature. Material chemist has an enormous role to play in this novel area, including development of efficient synthetic methodologies and control the molecular self-assembly and (opto)-electronic properties. The body of this thesis mainly focuses on the substituent effects: how different substituents affect the (opto)-electronic properties of the donor-acceptor (D-A) conjugated polymers. The main priority goes to understand, how different alkyl substituent effect to the polymer solubility, crystallinity, thermal properties (e.g.: glass transition temperature) and morphological order. Three classes of D-A systems were extensively studied in this work. The second chapter mainly focuses on the synthesis and structure-property study of fluorinated arene (TFB) base polymers. Here we used commercially available 1,4-dibromo-2,3,5,6-tetrafluorobenzene (TFB) as the acceptor material and prepare several polymers using 3,3'-dialkyl(3,3'-R2T2) or 3,3'-dialkoxy bithiophene (3,3'-RO2T2) units as electron donors. A detail study was done using 3,3'-bithiophene donor units incorporating branched alkoxy-functionalities by systematic variation of branching position and chain length. The study allowed disentangling the branching effects on (i) aggregation tendency, intermolecular arrangement, (iii) solid state optical energy gaps, and (iv) electronic properties in an overall consistent picture, which might guide future polymer synthesis towards optimized materials for opto-electronic applications. The third chapter mainly focused on

  9. Synthesis and immunological properties of Vi and di-O-acetyl pectin protein conjugates with adipic acid dihydrazide as the linker.

    Science.gov (United States)

    Kossaczka, Z; Bystricky, S; Bryla, D A; Shiloach, J; Robbins, J B; Szu, S C

    1997-06-01

    The Vi capsular polysaccharide of Salmonella typhi, a licensed vaccine for typhoid fever in individuals > or = 5 years old, induces low and short-lived antibodies in children, and reinjection does not elicit booster responses at any age. Its immunogenicity was improved by binding Vi to proteins by using N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as a linker. Similar findings were observed with the structurally related, di-O-acetyl derivative of pectin [poly-alpha(1-->4)-D-GalpA] designated OAcP. Protein conjugates of Vi and OAcP were synthesized by carbodiimide-mediated synthesis with adipic acid dihydrazide (ADH) as the linker. Hydrazide groups were introduced into proteins (bovine serum albumin or recombinant Pseudomonas aeruginosa exoprotein A) by treatment with ADH and 1-ethyl-3(3-dimethylaminopropyl carbodiimide (EDC). The resultant adipic acid hydrazide derivatives (AH-proteins), containing 2.3 to 3.4% AH, had antigenic and physicochemical properties similar to those of the native proteins. The AH-proteins were bound to Vi and OAcP by treatment with EDC. The immunogenicity of Vi or OAcP, alone or as protein conjugates, was evaluated in young outbred mice and guinea pigs by subcutaneous injection of 2.5 and 5.0 microg, respectively, of polysaccharide, and antibodies were measured by enzyme-linked immunosorbent assay. All conjugates were significantly more immunogenic than Vi or OAcP alone and induced booster responses with 5- to 25-fold increases of antibodies. Vi conjugates were significantly more immunogenic than their OAcP analogs. A carboxymethyl derivative of yeast beta-glucan enhanced the anti-Vi response elicited by an OAcP conjugate but had no effect on the immunogenicity of Vi or of OAcP alone. Vi and OAcP conjugates synthesized by this scheme will be evaluated clinically.

  10. Synthesis and luminescent properties of new conjugated polymers based on poly(p-phenylene vinylene)

    Science.gov (United States)

    Gurge, Ronald Matthew

    The "push-pull" electronically substituted polymers poly(2 (5) -bromo-5 (2) -n-hexyloxy-1,4-phenylene vinylene), poly(2 (5) -chloro-5 (2) -n-hexyloxy-1,4-phenylene vinylene) and poly(2 (5) -fluoro-5 (2) -n-hexyloxy-1,4-phenylene vinylene) were synthesized by a soluble precursor method and were used to fabricate light emitting diode (LED) devices. Thermal elimination of the polyether precursors gives final conjugated polymers as flexible red films. Precursor polymers can be spin-cast from solutions onto indium/tin oxide (ITO) pretreated quartz plates, then thermally converted to the final red polymers. Light emitting diode fabrication is then completed by the thin film vapor deposition of calcium, followed by aluminum. LED devices of the "push-pull" polymers give light emission in the 620-635 nm range. Two fluorinated polymers, poly(2-fluoro-1,4-phenylene vinylene) and poly(2,5-difluoro-1,4-phenylene vinylene) were investigated for their electroluminescent (EL) properties. LED's using these materials as emissive layers show substantial EL wavelength shifts (560 nm and 600 nm, respectively) relative to emission from unsubstituted poly(1,4-phenylene vinylene) (565 nm). These differences in EL emission can be attributed to the electronic effects of fluorine substitution. Synthetic strategies were developed for copolymeric materials based on poly(1,4-phenylene vinylene). The alternating block copolymer, poly (1,8-octanedioxy-2,6-dimethoxy-1,4-phenylene-1,2-ethenylene-1,4-phenylene-1,2-ethenylene-1,4-phenylene-1,2-ethenylene- 3,5-dimethoxy-1,4-phenylene) was synthesized by a modified Wittig polymerization utilizing trialkyl phosphonium salts. This resulted in a regiospecific trans-olefination reaction when compared to polymeric materials synthesized through the use of common triaryl-phosphonium salts. Harsh post-Wittig isomerization procedures using Isb2 were bypassed as a result of the high trans-cis ratio of the final copolymer. It was fully characterized using the

  11. Synthesis, estrogen receptor binding affinity and molecular docking of pyrimidine-piperazine-chromene and -quinoline conjugates.

    Science.gov (United States)

    Parveen, Iram; Ahmed, Naseem; Idrees, Danish; Khan, Parvez; Hassan, Md Imtaiyaz

    2017-09-15

    Substituted 2-amino-7-((6-(4-(2-hydroxyethyl) piperazin-1-yl)-2-methylpyrimidin-4-yl)oxy)-4-phenyl-4H-chromene-3-carbonitriles and 2-amino-7-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)oxy)-4-phenyl-1,4-dihydroquinoline-3-carbonitriles were synthesized via an efficient multi-component one pot synthesis under mild conditions. These compounds 1-20 were evaluated against human breast cancer cell lines (MCF-7) and human embryonic kidney cells (HEK293) for cytotoxic activities. Among them, compounds 6, 7, 15, 17 and 19 showed better anti-proliferative activities as (IC 50 value 48±1.70, 65±1.13, 92±1.18, 30±1.17 and 16±1.10µM) than curcumin drug (48±1.11µM). Molecular docking was also performed with active compounds 6, 7 and 15 against Bcl-2 protein which gave good binding affinity (ΔG=-9.08, -8.29 and -7.70kcal/mol) respectively. Furthermore, the structure-activity relationship (SAR) analysis revealed that the chromene and quinoline moieties, when attached with pyrimide and piperazine moieties, enhanced anti-proliferative activities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Synthesis and biological evaluation of porphyrin-polyamine conjugates as potential agents in photodynamic therapy

    International Nuclear Information System (INIS)

    Lamarche, Francois

    2004-01-01

    The synthesis of photosensitizers that specifically recognize tumoral cells constitutes a challenging step in the field of photodynamic therapy. To this end, we designed a new class of porphyrins linked to natural polyamines (spermidine, spermine). As a first step, we synthesized para and ortho-carboxy-propyl-oxy-phenyl-tritolyl-porphyrins bearing spermidine or spermine. Then, we designed two precursors, N4-aminobutyl-spermidine-Boc2 and N4-aminobutyl-spermine-Boc3. These derivatives have been fixed on carboxy-porphyrins, protoporphyrin IX and chlorin e6. These new compounds have been characterized by MALDI spectrometry, UV-Visible and 1 H NMR spectroscopy. They have been found to produce singlet oxygen. Biological activity study of these photosensitizers has been realized on K562 cell line, irradiated with fluorescent bulbs. In vitro tests of these porphyrins have shown their photo-cytotoxic activity and protoporphyrins-polyamines have been able to trigger early apoptotic events. Finally, preliminary results obtained with chlorin e6-polyamines, irradiated with red light, seem to show that these structures are good candidates for an application in PDT. (author) [fr

  13. Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes

    DEFF Research Database (Denmark)

    Obsen, Thomas; Faergeman, Nils J; Chung, Soonkyu

    2012-01-01

    ,12 CLA, but not 9,11 CLA, decreased total cellular lipids within 3 days and the ratio of monounsaturated FA (MUFA) to saturated FA, and increased C18:0 acyl-CoA levels within 24 h. Consistent with these data, stearoyl-CoA desaturase (SCD)-1 mRNA and protein levels were down-regulated by 10,12 CLA within...... metabolism. The lipid-lowering effects of 10,12 CLA were unique, as other trans FA did not reduce TG content to the same extent. Using low levels of [(14)C]-CLA isomers, it was shown that both isomers were readily incorporated into acylglycerols and phospholipids, albeit at lower levels than [(14)C...... 7-12 h, respectively. The mRNA levels of liver X receptor (LXR)α and sterol regulatory element binding protein (SREBP)-1c, transcription factors that regulate SCD-1, were decreased by 10,12 CLA within 5 h. These data suggest that the isomer-specific decrease in de novo lipid synthesis by 10,12 CLA...

  14. Effect of conjugated linoleic acid and acetate on milk fat synthesis and adipose lipogenesis in lactating dairy cows.

    Science.gov (United States)

    Urrutia, N; Harvatine, K J

    2017-07-01

    During biohydrogenation-induced milk fat depression (MFD), nutrients are spared from milk fat synthesis and are available for other metabolic uses. Acetate is the major carbon source spared and it may increase lipid synthesis in adipose tissue during MFD. The objective of this study was to compare the effect of trans-10,cis-12 conjugated linoleic acid (CLA) and the amount of acetate spared during CLA-induced MFD on adipose tissue lipogenesis. Nine multiparous, lactating, ruminally cannulated Holstein cows (244 ± 107 d in milk; 25 ± 8.4 kg of milk/d; mean ± standard deviation) were randomly assigned to treatments in a 3 × 3 Latin square design. Experimental periods were 4 d followed by a 10-d washout. Treatments were control (CON), ruminal infusion of acetate (AC; continuous infusion of 7 mol/d adjusted to pH 6.1 with sodium hydroxide), or abomasal infusion of CLA (10 g/d of both trans-10,cis-12 CLA and cis-9,trans-11 CLA). Dry matter intake, milk yield, and milk protein yield and percentage were not affected by treatments. Compared with CON, milk fat yield decreased 23% and fat percent decreased 28% in CLA, and milk fat yield increased 20% in AC. Concentration and yield of milk de novo synthesized fatty acids (acids (>C16) was increased by CLA, compared with CON. Yield of de novo synthesized fatty acids and palmitic acid was increased by AC, compared with CON. Lipogenesis capacity of adipose tissue explants was decreased 72% by CLA, but was not affected by AC. Acetate oxidation by adipose explants was not affected by treatments. Treatments had no effect on expression of key lipogenic factors, lipogenic enzymes, and leptin; however, expression of fatty acid binding protein 4 was reduced in CLA compared with CON. Additionally, hormone-sensitive lipase and perilipin 1 were decreased by CLA and acetate. Plasma glucose and glucagon concentrations were not affected by treatments; however, CLA increased nonesterified fatty acids 17.7%, β-hydroxybutyrate 16.1%, and

  15. The photochemical thiol-ene reaction as a versatile method for the synthesis of glutathioneS-conjugates targeting the bacterial potassium efflux system Kef.

    Science.gov (United States)

    Healy, Jess; Rasmussen, Tim; Miller, Samantha; Booth, Ian R; Conway, Stuart J

    2016-04-29

    The thiol-ene coupling reaction is emerging as an important conjugation reaction that is suitable for use in a biological setting. Here, we explore the utility of this reaction for the synthesis of glutathione- S -conjugates (GSX) and present a general, operationally simple, protocol with a wide substrate scope. The GSX afforded are an important class of compounds and provide invaluable molecular tools to study glutathione-binding proteins. In this study we apply the diverse library of GSX synthesised to further our understanding of the structural requirements for binding to the glutathione-binding protein, Kef, a bacterial K + efflux system, found in many bacterial pathogens. This system is vital to the survival of bacteria upon exposure to electrophiles, and plays an essential role in the maintenance of intracellular pH and K + homeostasis. Consequently, Kef is an appealing target for the development of novel antibacterial drugs.

  16. Synthesis, characterization, and antimicrobial activity of an ampicillin-conjugated magnetic nanoantibiotic for medical applications

    Directory of Open Access Journals (Sweden)

    Hussein-Al-Ali SH

    2014-08-01

    Full Text Available Samer Hasan Hussein-Al-Ali,1,2 Mohamed Ezzat El Zowalaty,3,4 Mohd Zobir Hussein,5 Benjamin M Geilich,6 Thomas J Webster6,7 1Laboratory of Molecular Biomedicine, 2Faculty of Pharmacy, Isra University, Amman, Kingdom of Jordan; 3Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 4Faculty of Public Health and Tropical Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia; 5Materials Synthesis and Characterization Laboratory Institute of Advanced Technology, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 6Department of Chemical Engineering and Program in Bioengineering, Northeastern University, Boston, MA, USA; 7Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia Abstract: Because of their magnetic properties, magnetic nanoparticles (MNPs have numerous diverse biomedical applications. In addition, because of their ability to penetrate bacteria and biofilms, nanoantimicrobial agents have become increasingly popular for the control of infectious diseases. Here, MNPs were prepared through an iron salt coprecipitation method in an alkaline medium, followed by a chitosan coating step (CS-coated MNPs; finally, the MNPs were loaded with ampicillin (amp to form an amp-CS-MNP nanocomposite. Both the MNPs and amp-CS-MNPs were subsequently characterized and evaluated for their antibacterial activity. X-ray diffraction results showed that the MNPs and nanocomposites were composed of pure magnetite. Fourier transform infrared spectra and thermogravimetric data for the MNPs, CS-coated MNPs, and amp-CS-MNP nanocomposite were compared, which confirmed the CS coating on the MNPs and the amp-loaded nanocomposite. Magnetization curves showed that both the MNPs and the amp-CS-MNP nanocomposites were superparamagnetic, with saturation magnetizations at 80.1 and 26.6 emu g-1, respectively. Amp was loaded at 8

  17. Organometallic DNA-B12 Conjugates as Potential Oligonucleotide Vectors: Synthesis and Structural and Binding Studies with Human Cobalamin-Transport Proteins.

    Science.gov (United States)

    Mutti, Elena; Hunger, Miriam; Fedosov, Sergey; Nexo, Ebba; Kräutler, Bernhard

    2017-11-16

    The synthesis and structural characterization of Co-(dN) 25 -Cbl (Cbl: cobalamin; dN: deoxynucleotide) and Co-(dN) 39 -Cbl, which are organometallic DNA-B 12 conjugates with single DNA strands consisting of 25 and 39 deoxynucleotides, respectively, and binding studies of these two DNA-Cbl conjugates to three homologous human Cbl transporting proteins, transcobalamin (TC), intrinsic factor (IF), and haptocorrin (HC), are reported. This investigation tests the suitability of such DNA-Cbls for the task of eventual in vivo oligonucleotide delivery. The binding of DNA-Cbl to TC, IF, and HC was investigated in competition with either a fluorescent Cbl derivative and Co-(dN) 25 -Cbl, or radiolabeled vitamin B 12 ( 57 Co-CNCbl) and Co-(dN) 25 -Cbl or Co-(dN) 39 -Cbl. Binding of the new DNA-Cbl conjugates was fast and tight with TC, but poorer with HC and IF, which extends a similar original finding with the simpler DNA-Cbl, Co-(dN) 18 -Cbl. The contrasting affinities of TC versus IF and HC for the DNA-Cbl conjugates are rationalized herein by a stepwise mechanism of Cbl binding. Critical contributions to overall affinity result from gradual conformational adaptations of the Cbl-binding proteins to the DNA-Cbl, which is first bound to the respective β domains. This transition is fast with TC, but slow with IF and HC, with which weaker binding results. The invariably tight interaction of the DNA-Cbl conjugates with TC makes the Cbl moiety a potential natural vector for the specific delivery of oligonucleotide loads from the blood into cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Chemo-Enzymatic Synthesis of Glycolyl-Ester-Linked Taxol-Monosaccharide Conjugate and Its Drug Delivery System Using Hepatitis B Virus Envelope L Bio-Nanocapsules

    Directory of Open Access Journals (Sweden)

    Kei Shimoda

    2012-01-01

    Full Text Available Chemo-enzymatic synthesis of glycolyl-ester-linked taxol-glucose conjugate, ie, 7-glycolyltaxol 2′- O -α-D-glucoside, was achieved by using α-glucosidase as a biocatalyst. The water-solubility of 7-glycolyltaxol 2′- O -α-D-glucoside (21 μM was 53 fold higher than that of taxol. The hepatitis B virus envelope L particles (bio-nanocapsules are effective for delivering 7-glycolyltaxol 2′- O -α-D-glucoside to human hepatocellular carcinoma NuE cells.

  19. Synthesis, spectroscopic, and photophysical characterization and photosensitizing activity toward prokaryotic and eukaryotic cells of porphyrin-magainin and -buforin conjugates.

    Science.gov (United States)

    Dosselli, Ryan; Ruiz-González, Rubén; Moret, Francesca; Agnolon, Valentina; Compagnin, Chiara; Mognato, Maddalena; Sella, Valentina; Agut, Montserrat; Nonell, Santi; Gobbo, Marina; Reddi, Elena

    2014-02-27

    Cationic antimicrobial peptides (CAMPs) and photodynamic therapy (PDT) are attractive tools to combat infectious diseases and to stem further development of antibiotic resistance. In an attempt to increase the efficiency of bacteria inactivation, we conjugated a PDT photosensitizer, cationic or neutral porphyrin, to a CAMP, buforin or magainin. The neutral and hydrophobic porphyrin, which is not photoactive per se against Gram-negative bacteria, efficiently photoinactivated Escherichia coli after conjugation to either buforin or magainin. Conjugation to magainin resulted in the considerable strengthening of the cationic and hydrophilic porphyrin's interaction with the bacterial cells, as shown by the higher bacteria photoinactivation activity retained after washing the bacterial suspension. The porphyrin-peptide conjugates also exhibited strong interaction capability as well as photoactivity toward eukaryotic cells, namely, human fibroblasts. These findings suggest that these CAMPs have the potential to carry drugs and other types of cargo inside mammalian cells similar to cell-penetrating peptides.

  20. Synthesis and antibody conjugation of magnetic nanoparticles with improved specific power absorption rates for alternating magnetic field cancer therapy

    International Nuclear Information System (INIS)

    Gruettner, Cordula; Mueller, Knut; Teller, Joachim; Westphal, Fritz; Foreman, Allan; Ivkov, Robert

    2007-01-01

    Bionized nanoferrite (BNF) particles with high specific power absorption rates were synthesized in the size range of 20-100 nm by high-pressure homogenization for targeted cancer therapy with alternating magnetic fields. Several strategies were used to conjugate antibodies to the BNF particles. These strategies were compared using an immunoassay to find optimal conditions to reach a high immunoreactivity of the final antibody-particle conjugate

  1. Design and Synthesis of New Cholesterol-Conjugated 5-Fluorouracil: A Novel Potential Delivery System for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Awwad A. Radwan

    2014-08-01

    Full Text Available Cholesterol-conjugated 5-fluorouracil prodrugs were designed to be carried in vivo via low density lipoproteins (LDL and subsequently undergo LDL-receptor-mediated internalisation into cancer cells. In vivo anti-cancer evaluation was performed using 5-fluorouracil-cholesterol conjugate in a mouse model. The obtained prodrugs were more potent than 5-fluorouracil control drug at the same 5-fluorouracil content (3 mg·kg−1.

  2. [Optimizing synthesis of conjugates of superoxide dismutase and catalase with aldehyde dextrans in surfactant microemulsions in heptane].

    Science.gov (United States)

    Eremin, A N; Metelitsa, D I

    1997-01-01

    Stable microemulsions in heptane retaining considerable amounts of the polar phase were obtained by using Aerosol OT (AOT), Triton X-45, and catalase. Conjugates of superoxide dismutase (SOD) and catalase with aldehyde dextrans (AD) were synthesized in surfactant microemulsions in heptane. Effects of the reaction duration, the microemulsion polar phase volume, and concentrations of enzymes and modifiers on the properties of these conjugates were studied. The catalytic properties of conjugates depended on the nature of the surfactants used to stabilize the microemulsions, the initial concentration of protein in the reaction mixture, and the enzyme: modifier ratio. The degree of modification of the enzymes and the stabilities of their conjugates during isolation from microemulsions by a water-acetone solution depended on the concentration of the AD used. The catalytic properties of the conjugates synthesized were compared, and their stabilities in the presence of H2O2 were described. We suggested a simple method of transformation of whole kinetic curves of H2O2 conversion in coordinates 1/ln([H2O2]0/[H2O2]t - 1/t for simultaneous measurement of the constant of the catalase inactivation rate by H2O2 (Cin, S-1) and the rate constant of the catalase complex 1 interaction with the second H2O2 molecule (C2, M-1 S-1). This method was tested experimentally. Values C2 and Cin for catalase and its conjugates with ADs were compared, and these results were discussed.

  3. Novel Antitumor Platinum(II) Conjugates Containing the Nonsteroidal Anti-inflammatory Agent Diclofenac: Synthesis and Dual Mechanisms of Antiproliferative Effects.

    Science.gov (United States)

    Intini, Francesco Paolo; Zajac, Juraj; Novohradsky, Vojtech; Saltarella, Teresa; Pacifico, Concetta; Brabec, Viktor; Natile, Giovanni; Kasparkova, Jana

    2017-02-06

    One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines. One of these compounds, compound 3, in which DCF molecules are coordinated to Pt(II) through their carboxylic group, is more potent than parental conventional Pt(II) drug cisplatin, free DCF and the congeners of 3 in which DCF ligands are conjugated to Pt(II) via a diamine. The potency of 3 is due to several factors including enhanced internalization that correlates with enhanced DNA binding and cytotoxicity. Mechanistic studies show that 3 combines multiple effects. After its accumulation in cells, it releases Pt(II) drug capable of binding/damaging DNA and DCF ligands, which affect distribution of cells in individual phases of the cell cycle, inhibit glycolysis and lactate transport, collapse mitochondrial membrane potential, and suppress the cellular properties characteristic of metastatic progression.

  4. Real-Time Analysis on Drug-Antibody Ratio of Antibody-Drug Conjugates for Synthesis, Process Optimization, and Quality Control.

    Science.gov (United States)

    Tang, Yubo; Tang, Feng; Yang, Yang; Zhao, Lei; Zhou, Hu; Dong, Jinhua; Huang, Wei

    2017-08-10

    Drug-antibody ratio (DAR) of antibody-drug conjugates (ADCs) is important for their therapeutic efficacy and pharmacokinetics, therefore control on DAR in synthesis process is a key for ADC quality control. Although various analytical methods were reported, the real-time monitoring on DAR is still a challenge because time-consuming sample preparation is usually needed during the analysis. Antibody deglycosylation of ADC simplifies DAR measurement, however long-time PNGaseF digestion for deglycosylation hampers the real-time detection. Here, we report a rapid DAR analysis within 15 min by robust deglycosylation treatment and LC-MS detection that enables real-time DAR monitoring for optimization on ADC synthetic process. With this approach, we were able to screen suitable conjugation conditions efficiently and afford the ADCs with expected DARs. To the best of our knowledge, this is the first report on real-time DAR analysis of ADCs for conjugation optimization and quality control, compatible with random lysine-linked ADCs, glycosite-specific ADCs, and the complicated dual-payload ADCs.

  5. Glucuronide and Sulfate Conjugates of Bisphenol A: Chemical Synthesis and Correlation Between Their Urinary Levels and Plasma Bisphenol A Content in Voluntary Human Donors.

    Science.gov (United States)

    Ho, Ka-Lok; Yuen, Ka-Ki; Yau, Man-Shan; Murphy, Margaret B; Wan, Yi; Fong, Bonnie M-W; Tam, Sidney; Giesy, John P; Leung, Kelvin S-Y; Lam, Michael H-W

    2017-10-01

    Bisphenol A (BPA) glucuronide and sulfate conjugates are major products of Phase II metabolism of BPA in humans. In the past, their determination in body fluids usually involves tedious enzymatic hydrolysis and multiresidual analysis. The recent availability of authentic standards of these conjugates enables our better understand of the human metabolism of BPA and the distribution of their metabolites in body fluids. In this work, we report the chemical synthesis and purification of BPA mono- and di-glucuronide and BPA mono- and di-sulfate. Their levels, as well as that of BPA, in 140 paired human plasma and urine samples collected randomly from voluntary donors in Hong Kong SAR, China, were determined by solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS). BPA was found in more than 135 human plasma and urine samples. Its Phase II metabolites, ranging from N.D. to 36.7 µg g -1 -creatinine, also were detected in 139 of the 140 urine samples. Good correlation (r = 0.911) between molar concentration of BPA in the plasma and that of "total urinary BPA" (i.e., ln [(BPA + ∑ BPA phase II conjugate) molar concentration ]) was observed. Direct quantification of Phase II metabolites of BPA in human urine can be a useful assessment tool for population exposure to this potent endocrine disrupting chemical.

  6. Synthesis of sugars embodying conjugated carbonyl systems and related triazole derivatives from carboxymethyl glycoside lactones. Evaluation of their antimicrobial activity and toxicity.

    Science.gov (United States)

    Xavier, Nuno M; Goulart, Margarida; Neves, Ana; Justino, Jorge; Chambert, Stéphane; Rauter, Amélia P; Queneau, Yves

    2011-01-15

    The synthesis of a series of pyranoid derivatives comprising a conjugated carbonyl function and related triazole derivatives, structurally suitable for bioactivity evaluation, was achieved in few steps starting from readily available carboxymethyl glycoside lactones (CMGL). 3-Enopyranosid-2-uloses were generated by oxidation/elimination of tri-O-acylated 2-hydroxy pyranosides. Subsequent Wittig olefination provided stereoselectively 2-C-branched-chain conjugated dienepyranosides with (E)-configuration around the exocyclic double bond. A heterogeneous CuI/Amberlyst-catalyzed 'click' chemistry protocol was used to convert glycosides bearing a propargyl moiety into the corresponding 1,2,3-triazoles. These new molecules were screened for their in vitro antibacterial and antifungal activities and those containing conjugated carbonyl systems demonstrated the best efficacy. (N-Dodecylcarbamoyl)methyl enone glycerosides were the most active ones among the enones tested. The α-anomer displayed very strong activities against Bacillus cereus and Bacillus subtilis and strong activity toward Enterococcus faecalis and the fungal pathogen Penicillium aurantiogriseum. The corresponding β-anomer presented a very strong inhibitory effect against two fungal species (Aspergillus niger and P. aurantiogriseum). (N-Dodecyl-/N-propargyl/or N-benzylcarbamoyl)methyl dienepyranosides exhibited selectively a strong activity toward E. faecalis. Further acute toxicity evaluation indicated low toxic effect of the (N-dodecylcarbamoyl)methyl enone glyceroside α-anomer and of the carbamoylmethyl dienepyranosides N-protected with propargyl or benzyl groups. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Design and synthesis of imidazo[2,1-b]thiazole-chalcone conjugates: microtubule-destabilizing agents.

    Science.gov (United States)

    Kamal, Ahmed; Balakrishna, Moku; Nayak, V Lakshma; Shaik, Thokhir Basha; Faazil, Shaikh; Nimbarte, Vijaykumar D

    2014-12-01

    A series of chalcone conjugates featuring the imidazo[2,1-b]thiazole scaffold was designed, synthesized, and evaluated for their cytotoxic activity against five human cancer cell lines (MCF-7, A549, HeLa, DU-145 and HT-29). These new hybrid molecules have shown promising cytotoxic activity with IC50 values ranging from 0.64 to 30.9 μM. Among them, (E)-3-(6-(4-fluorophenyl)-2,3-bis(4-methoxyphenyl)imidazo[2,1-b]thiazol-5-yl)-1-(pyridin-2-yl)prop-2-en-1-one (11 x) showed potent antiproliferative activity with IC50 values ranging from 0.64 to 1.44 μM in all tested cell lines. To investigate the mechanism of action, the detailed biological aspects of this promising conjugate (11 x) were carried out on the A549 lung cancer cell line. The tubulin polymerization assay and immunofluoresence analysis results suggest that this conjugate effectively inhibits microtubule assembly in A549 cells. Flow cytometric analysis revealed that this conjugate induces cell-cycle arrest in the G2/M phase and leads to apoptotic cell death. This was further confirmed by Hoechst staining, activation of caspase-3, DNA fragmentation analysis, and Annexin V-FITC assay. Moreover, molecular docking studies indicated that this conjugate (11 x) interacts and binds efficiently with the tubulin protein. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Molecular-target-based anticancer photosensitizer: synthesis and in vitro photodynamic activity of erlotinib-zinc(II) phthalocyanine conjugates.

    Science.gov (United States)

    Zhang, Feng-Ling; Huang, Qi; Liu, Jian-Yong; Huang, Ming-Dong; Xue, Jin-Ping

    2015-02-01

    Targeted photodynamic therapy is a new promising therapeutic strategy to overcome growing problems in contemporary medicine, such as drug toxicity and drug resistance. A series of erlotinib-zinc(II) phthalocyanine conjugates were designed and synthesized. Compared with unsubstituted zinc(II) phthalocyanine, these conjugates can successfully target EGFR-overexpressing cancer cells owing to the presence of the small molecular-target-based anticancer agent erlotinib. All conjugates were found to be essentially non-cytotoxic in the absence of light (up to 50 μM), but upon illumination, they show significantly high photo-cytotoxicity toward HepG2 cells, with IC50 values as low as 9.61-91.77 nM under a rather low light dose (λ=670 nm, 1.5 J cm(-2) ). Structure-activity relationships for these conjugates were assessed by determining their photophysical/photochemical properties, cellular uptake, and in vitro photodynamic activities. The results show that these conjugates are highly promising antitumor agents for molecular-target-based photodynamic therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Novel Selective Estrogen Receptor Ligand Conjugates Incorporating Endoxifen-Combretastatin and Cyclofenil-Combretastatin Hybrid Scaffolds: Synthesis and Biochemical Evaluation

    Directory of Open Access Journals (Sweden)

    Patrick M. Kelly

    2017-08-01

    Full Text Available Nuclear receptors such as the estrogen receptors (ERα and ERβ modulate the effects of the estrogen hormones and are important targets for design of innovative chemotherapeutic agents for diseases such as breast cancer and osteoporosis. Conjugate and bifunctional compounds which incorporate an ER ligand offer a useful method of delivering cytotoxic drugs to tissue sites such as breast cancers which express ERs. A series of novel conjugate molecules incorporating both the ER ligands endoxifen and cyclofenil-endoxifen hybrids covalently linked to the antimitotic and tubulin targeting agent combretastatin A-4 were synthesised and evaluated as ER ligands. A number of these compounds demonstrated pro-apoptotic effects, with potent antiproliferative activity in ER-positive MCF-7 breast cancer cell lines and low cytotoxicity. These conjugates displayed binding affinity towards ERα and ERβ isoforms at nanomolar concentrations e.g., the cyclofenil-amide compound 13e is a promising lead compound of a clinically relevant ER conjugate with IC50 in MCF-7 cells of 187 nM, and binding affinity to ERα (IC50 = 19 nM and ERβ (IC50 = 229 nM while the endoxifen conjugate 16b demonstrates antiproliferative activity in MCF-7 cells (IC50 = 5.7 nM and binding affinity to ERα (IC50 = 15 nM and ERβ (IC50 = 115 nM. The ER binding effects are rationalised in a molecular modelling study in which the disruption of the ER helix-12 in the presence of compounds 11e, 13e and 16b is presented These conjugate compounds have potential application for further development as antineoplastic agents in the treatment of ER positive breast cancers.

  10. Synthesis, characterization and target protein binding of drug-conjugated quantum dots in vitro and in living cells

    International Nuclear Information System (INIS)

    Choi, Youngseon; Kim, Minjung; Cho, Yoojin; Yun, Eunsuk; Song, Rita

    2013-01-01

    Elucidation of unknown target proteins of a drug is of great importance in understanding cell biology and drug discovery. There have been extensive studies to discover and identify target proteins in the cell. Visualization of targets using drug-conjugated probes has been an important approach to gathering mechanistic information of drug action at the cellular level. As quantum dot (QD) nanocrystals have attracted much attention as a fluorescent probe in the bioimaging area, we prepared drug-conjugated QD to explore the potential of target discovery. As a model drug, we selected a well-known anticancer drug, methotrexate (MTX), which has been known to target dihydrofolate reductase (DHFR) with high affinity binding (K d = 0.54 nM). MTX molecules were covalently attached to amino-PEG-polymer-coated QDs. Specific interactions of MTX-conjugated QDs with DHFR were identified using agarose gel electrophoresis and fluorescence microscopy. Cellular uptake of the MTX-conjugated QDs in living CHO cells was investigated with regard to their localization and distribution pattern. MTX–QD was found to be internalized into the cells via caveolae-medicated endocytosis without significant sequestration in endosomes. A colocalization experiment of the MTX–QD conjugate with antiDHFR-TAT-QD also confirmed that MTX–QD binds to the target DHFR. This study showed the potential of the drug-QD conjugate to identify or visualize drug–target interactions in the cell, which is currently of great importance in the area of drug discovery and chemical biology. (paper)

  11. Synthesis of nano-bio conjugates for drug delivery systems using gas-liquid interfacial discharge plasmas

    International Nuclear Information System (INIS)

    Kaneko, Toshiro; Chen, Qiang; Hatakeyama, Rikizo

    2012-01-01

    Size-controlled gold nanoparticles (AuNPs) covered with DNA are synthesized by using a pulse driven gas-liquid interfacial discharge plasma (GLIDP) to reduce an aqueous solution of chloroauric acid trihydrate with DNA. The size and the assembly of the AuNPs are found to be easily controlled by changing the DNA concentration in the aqueous solution. The synthesized AuNP-DNA conjugates are forced to be encapsulated into double-walled carbon nanotubes (DWNTs) by superimposing a positive DC voltage on the pulse voltage. The AuNP-DNA-conjugate encapsulated DWNTs can be utilized in drug delivery systems when DNA is used as a drug molecule.

  12. Design and synthesis of imidazo[2,1-b]thiazole linked triazole conjugates: Microtubule-destabilizing agents.

    Science.gov (United States)

    Shaik, Siddiq Pasha; Nayak, V Lakshma; Sultana, Faria; Rao, A V Subba; Shaik, Anver Basha; Babu, Korrapati Suresh; Kamal, Ahmed

    2017-01-27

    A series of imidazo[2,1-b]thiazole linked triazole conjugates were synthesized by using Huisgen 1,3-dipolar cyclo-addition reaction (click chemistry approach) and evaluated for their antiproliferative activity against some human cancer cell lines like, HeLa (cervical), DU-145 (prostate), A549 (lung), MCF-7 (breast) and HepG2 (liver). Among them, Conjugates 4g and 4h demonstrated a significant antiproliferative effect against human lung cancer cells (A549) with IC 50 values of 0.92 and 0.78 μM respectively. Flow cytometric analysis revealed that these conjugates induced cell cycle arrest in G2/M phase in A549 lung cancer cells. The tubulin polymerization assay and immunofluorescence analysis showed that these conjugates effectively inhibit microtubule assembly in cell free and cell based (A549) experiment respectively. Moreover, the apoptosis inducing properties were evaluated by Hoechst staining, mitochondrial membrane potential and Annexin V-FITC assay. Further, western blot analysis was performed for proapoptotic protein Bax and antiapoptotic protein Bcl-2 and the results demonstrated that there was up regulation of Bax and down regulation of Bcl-2 suggesting that these compounds induced apoptosis in human lung cancer cells, A549. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Synthesis of multi-galactose-conjugated 2'-O-methyl oligoribonucleotides and their in vivo imaging with positron emission tomography.

    Science.gov (United States)

    Mäkilä, Jussi; Jadhav, Satish; Kiviniemi, Anu; Käkelä, Meeri; Liljenbäck, Heidi; Poijärvi-Virta, Päivi; Laitala-Leinonen, Tiina; Lönnberg, Harri; Roivainen, Anne; Virta, Pasi

    2014-12-15

    (68)Ga labelled 2'-O-methyl oligoribonucleotides (anti-miR-15b) bearing one, three or seven d-galactopyranoside residues have been prepared and their distribution in healthy rats has been studied by positron emission tomography (PET). To obtain the heptavalent conjugate, an appropriately protected 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) precursor bearing a 4-[4-(4,4'-dimethoxytrityloxy)butoxy]phenyl side arm was first immobilized via a base labile linker to the support and the oligonucleotide was assembled on the detritylated hydroxyl function of this handle. A phosphoramidite building block bearing two phthaloyl protected aminooxy groups and one protected hydroxyl function was introduced into the 5'-terminus. One acetylated galactopyranoside was coupled as a phosphoramidite to the hydroxyl function, the phthaloyl protections were removed on-support and two trivalent galactopyranoside clusters were attached as aldehydes by on-support oximation. A two-step cleavage with aqueous alkali and ammonia released the conjugate in a fully deprotected form, allowing radiolabelling with (68)Ga in solution. The mono- and tri-galactose conjugates were obtained in a closely related manner. In vivo imaging in rats with PET showed remarkable galactose-dependent liver targeting of the conjugates. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. 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)

  15. Synthesis of ciprofloxacin-conjugated poly (L-lactic acid polymer for nanofiber fabrication and antibacterial evaluation

    Directory of Open Access Journals (Sweden)

    Parwe SP

    2014-03-01

    Full Text Available Sharad P Parwe, Priti N Chaudhari, Kavita K Mohite, Balaji S Selukar, Smita S Nande, Baijayantimala Garnaik Polymer Science and Engineering Division, National Chemical Laboratory, Pune, India Abstract: Ciprofloxacin was conjugated with polylactide (PLA via the secondary amine group of the piperazine ring using PLA and 7-(4-(2-Chloroacetyl piperazin-1-yl-1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid. Zinc prolinate, a biocompatible catalyst was synthesized, characterized, and used in ring opening polymerization of L-lactide. Five different kinds of OH-terminated poly(L-lactide (two-, three-, four-, six-arm, star-shaped homopolymers were synthesized by ring opening polymerization of L-lactide in the presence of dodecanol, glycerol, pentaerythritol, dipentaerythritol as initiator and zinc prolinate as a catalyst. The structures of the polymers and conjugates were thoroughly characterized by means of gel permeation chromatography, matrix-assisted laser desorption/ionization – time of flight mass spectrometry, and nuclear magnetic resonance spectroscopy. PLA (molecular weight =100,000 and ciprofloxacin conjugated PLA were used for fabrication of nonwoven nanofiber mat (diameter ranges; 150–400 nm having pore size (62–102 nm using electrospinning. The microbiological assessment shows that the release of ciprofloxacin possesses antimicrobial activity. The drug-release behavior of the mat was studied to reveal potential application as a drug delivery system. The result shows that the ciprofloxacin release rates of the PLA conjugate nonwoven nanofiber mat could be controlled by the drug loading content and the release medium. The development of a biodegradable ciprofloxacin system, based on nonwoven nanofiber mat, should be of great interest in drug delivery systems. Keywords: zinc prolinate, ciprofloxacin conjugated polylactides, CP-PLA, electrospinning, nonwoven nanofibers, drug release, antibacterial activity, MDR

  16. Synthesis of DOTA-conjugated multimeric [Tyr3]octreotide peptides via a combination of Cu(I)-catalyzed "click" cycloaddition and thio acid/sulfonyl azide "sulfo-click" amidation and their in vivo evaluation.

    NARCIS (Netherlands)

    Yim, C.B.; Dijkgraaf, I.; Merkx, R.; Versluis, C.; Eek, A.; Mulder, G.E.; Rijkers, D.T.; Boerman, O.C.; Liskamp, R.M.

    2010-01-01

    Herein, we describe the design, synthesis, and biological evaluation of a series of DOTA-conjugated monomeric, dimeric, and tetrameric [Tyr(3)]octreotide-based analogues as a tool for tumor imaging and/or radionuclide therapy. These compounds were synthesized using a Cu(I)-catalyzed 1,3-dipolar

  17. Synthesis and Characterization of Cefotaxime Conjugated Gold Nanoparticles and Their Use to Target Drug-Resistant CTX-M-Producing Bacterial Pathogens.

    Science.gov (United States)

    Shaikh, Sibhghatulla; Rizvi, Syed Mohd Danish; Shakil, Shazi; Hussain, Talib; Alshammari, Thamir M; Ahmad, Waseem; Tabrez, Shams; Al-Qahtani, Mohammad H; Abuzenadah, Adel M

    2017-09-01

    Multidrug-resistance due to "β lactamases having the expanded spectrum" (ESBLs) in members of Enterobacteriaceae is a matter of continued clinical concern. CTX-M is among the most common ESBLs in Enterobacteriaceae family. In the present study, a nanoformulation of cefotaxime was prepared using gold nanoparticles to combat drug-resistance in ESBL producing strains. Here, two CTX-M-15 positive cefotaxime resistant bacterial strains (i.e., one Escherichia coli and one Klebsiella pneumoniae strain) were used for testing the efficacy of "cefotaxime loaded gold-nanoparticles." Bromelain was used for both reduction and capping in the process of synthesis of gold-nanoparticles. Thereafter, cefotaxime was conjugated onto it with the help of activator 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide. For characterization of both unconjugated and cefotaxime conjugated gold nanoparticles; UV-Visible spectroscopy, Scanning, and Transmission type Electron Microscopy methods accompanied with Dynamic Light Scattering were used. We used agar diffusion method plus microbroth-dilution method for the estimation of the antibacterial-activity and determination of minimum inhibitory concentration or MIC values, respectively. MIC values of cefotaxime loaded gold nanoparticles against E. coli and K. pneumoniae were obtained as 1.009 and 2.018 mg/L, respectively. These bacterial strains were completely resistant to cefotaxime alone. These results reinforce the utility of conjugating an old unresponsive antibiotic with gold nanoparticles to restore its efficacy against otherwise resistant bacterial pathogens. J. Cell. Biochem. 118: 2802-2808, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Synthesis and organisation of poly-substituted porphyrins in thin films for the elaboration of a highly conjugated 2D polymer

    International Nuclear Information System (INIS)

    Da Cruz, Fernande

    1997-01-01

    This research thesis addresses the production and characterization of organic thin layers for the elaboration of a wholly conjugated bi-dimensional polymer. The author first reports the synthesis of molecules belonging to the substituted porphyrin family substituted by reactive functions (acetylenic and thiophene functions). He reports how these molecules are organised under the form of a plane paving by using the Langmuir-Blodgett (LB) technique and self-assembly. It has been possible to obtain steady and organised LB films from one the synthesized porphyrins. A new method of organisation based on self-assembly has been developed, and allowed polymerizable organised porphyrin single layers to be obtained. This opens a promising way to the production of the bi-dimensional polymer. Thin films have been characterized by UV-visible spectrophotometry, IR spectrometry, X-ray diffraction, and linear dichroism [fr

  19. Synthesis of conjugates of 6-aminophenanthridine and guanabenz, two structurally unrelated prion inhibitors, for the determination of their cellular targets by affinity chromatography.

    Science.gov (United States)

    Gug, Fabienne; Oumata, Nassima; Tribouillard-Tanvier, Déborah; Voisset, Cécile; Desban, Nathalie; Bach, Stéphane; Blondel, Marc; Galons, Hervé

    2010-02-17

    The synthesis of affinity matrices for 6-aminophenanthridine (6AP) and 2,6-dichlorobenzylidenaminoguanidine (Guanabenz, GA), two unrelated prion inhibitors, is described. In both cases, the same simple spacer, epsilon-aminocaproylaminopentanol, was introduced by a Mitsunobu reaction and the choice of the anchoring position of the linker was determined by the study of the residual antiprion activity of the corresponding 6AP or GA conjugates. Very recently, these two affinity matrices were used for chromatography assays leading to the identification of ribosome (via the rRNA) as a common target of these two antiprion drugs. Here, we show, using competition experiments with Quinacrine (QC) and Chlorpromazine (CPZ), two other antiprion drugs, that QC, but not CPZ, may also directly target the rRNA.

  20. Synthesis of novel 1H-1,2,3-triazole tethered C-5 substituted uracil-isatin conjugates and their cytotoxic evaluation

    KAUST Repository

    Kumar, Kewal

    2012-12-01

    The present manuscript describes the synthesis of uracil-isatin hybrids via azide-alkyne cycloadditions and their cytotoxic evaluation against three human cancer cell lines viz. HeLa (cervix), MCF-7 (breast) and DU145 (prostate) using MTT assay. The evaluation studies revealed the dependence of cytotoxicity on C-5 substituents of both uracil and isatin as well as the alkyl chain length with compounds 6g and 6k showing IC50 values 18.21 and 13.90 μM respectively against DU145 cell lines. Most of the synthesized conjugates exhibited considerable selectivity against MCF-7 and DU145 cell lines. © 2012 Elsevier Masson SAS. All rights reserved.

  1. Synthesis and antiulcer activity evaluation of conjugates of amino acids with N-aroyl- N, N'-dicyclohexyl urea

    Directory of Open Access Journals (Sweden)

    Subudhi Bharat

    2011-12-01

    Full Text Available Abstract Amino acids are safe molecules with variable efficacy against ulceration. Considering the good antioxidant potential of N-aroyl- N, N'-dicyclohexyl urea and antiulcer activities of amino acids, a series of amino acid conjugates of N-aroyl- N, N'-dicyclohexyl urea was synthesized and the effect against ulceration in albino rats induced by pyloric ligation was screened. All these compounds were found to be safe and active. Reduction of ulcer index was significant for all compounds. Conjugates of methionine and histidine exhibited enhanced antiulcer activity comparable to omeprazole in terms of inhibition of release of gastric juice, hydrochloric acid and neutralization activity. The promising efficacy and safety of these compounds is interesting for further investigation.

  2. Synthesis and biological evaluation of imidazo[2,1-b]thiazole-benzimidazole conjugates as microtubule-targeting agents.

    Science.gov (United States)

    Baig, Mirza Feroz; Nayak, V Lakshma; Budaganaboyina, Prasad; Mullagiri, Kishore; Sunkari, Satish; Gour, Jitendra; Kamal, Ahmed

    2018-02-12

    A series of imidazo[2,1-b]thiazole-benzimidazole conjugates were synthesized and evaluated for their antiproliferative activity against four human cancer cell lines i.e.; HeLa (cervical), A549 (lung), MCF-7 (breast) and DU-145 (prostate) along with normal HEK-293 cell line. Amongst them, conjugate 6d displayed significant cytotoxicity against human lung cancer cell line, A549 with IC 50 value 1.08 µM. Further, cell cycle analysis revealed that this compound arrested the cell cycle at G2/M phase in A549 cells. Furthermore, the tubulin polymerization assay results suggest that this conjugate (6d) exhibits significant inhibitory effect on the tubulin assembly with an IC50 value of 1.68 µM. Moreover, the apoptotic inducing properties of compound 6d was confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and annexin V-FITC assay. Further, molecular docking studies revealed that compound 6d occupied the colchicine binding site. Copyright © 2018. Published by Elsevier Inc.

  3. Peptide dendrimer-conjugates of ketoprofen: Synthesis and ex vivo and in vivo evaluations of passive diffusion, sonophoresis and iontophoresis for skin delivery.

    Science.gov (United States)

    Hegde, Aswathi R; Rewatkar, Prarthana V; Manikkath, Jyothsna; Tupally, Karnaker; Parekh, Harendra S; Mutalik, Srinivas

    2017-05-01

    The aim of this study was to evaluate skin delivery of ketoprofen when covalently tethered to mildly cationic (2 + or 4 + ) peptide dendrimers prepared wholly by solid phase peptide synthesis. The amino acids glycine, arginine and lysine formed the dendrimer with ketoprofen tethered either to the lysine side-arm (N ε ) or periphery of dendrimeric branches. Passive diffusion, sonophoresis- and iontophoresis-assisted permeation of each peptide dendrimer-drug conjugate (D1-D4) was studied across mouse skin, both in vitro and in vivo. In addition, skin toxicity of dendrimeric conjugates when trialed with iontophoresis or sonophoresis was also evaluated. All dendrimeric conjugates improved aqueous solubility at least 5-fold, compared to ketoprofen alone, while also exhibiting appreciable lipophilicity. In vitro passive diffusion studies revealed that ketoprofen in its native form was delivered to a greater extent, compared with a dendrimer-conjugated form at the end of 24h (Q 24h (μg/cm 2 ): ketoprofen (68.06±3.62)>D2 (49.62±2.92)>D4 (19.20±0.89)>D1 (6.45±0.40)>D3 (2.21±0.19). However, sonophoresis substantially increased the skin permeation of ketoprofen-dendrimer conjugates in 30min (Q 30min (μg/cm 2 ): D4 (122.19±7.14)>D2 (66.74±3.86)>D1 (52.10±3.22)>D3 (41.66±3.22)) although ketoprofen alone again proved superior (Q 30min : 167.99±9.11μg/cm 2 ). Next, application of iontophoresis was trialed and shown to considerably increase permeation of dendrimeric ketoprofen in 6h (Q 6h (μg/cm 2 ): D2 (711.49±39.14)>D4 (341.23±16.43)>D3 (89.50±4.99)>D1 (50.91±2.98), with a Q 6h value of 96.60±5.12μg/cm 2 for ketoprofen alone). In vivo studies indicated that therapeutically relevant concentrations of ketoprofen could be delivered transdermally when iontophoresis was paired with D2 (985.49±43.25ng/mL). Further, histopathological analysis showed that the dendrimeric approach was a safe mode as ketoprofen alone. The present study successfully demonstrates that

  4. Gd-Complexes of New Arylpiperazinyl Conjugates of DTPA-Bis(amides: Synthesis, Characterization and Magnetic Relaxation Properties

    Directory of Open Access Journals (Sweden)

    Abdullah O. Ba-Salem

    2015-04-01

    Full Text Available Two new DTPA-bis(amide based ligands conjugated with the arylpiperazinyl moiety were synthesized and subsequently transformed into their corresponding Gd(III complexes 1 and 2 of the type [Gd(LH2O]·nH2O. The relaxivity (R1 of these complexes was measured, which turned out to be comparable with that of Omniscan®, a commercially available MRI contrast agent. The cytotoxicity studies of these complexes indicated that they are non-toxic, which reveals their potential and physiological suitability as MRI contrast agents. All the synthesized ligands and complexes were characterized with the aid of analytical and spectroscopic methods, including elemental analysis, 1H-NMR, FT-IR, XPS and fast atom bombardment (FAB mass spectrometry.

  5. Synthesis, photophysical and electrochemical properties, and protein-binding studies of luminescent cyclometalated iridium(III) bipyridine estradiol conjugates.

    Science.gov (United States)

    Lo, Kenneth Kam-Wing; Zhang, Kenneth Yin; Chung, Chi-Keung; Kwok, Karen Ying

    2007-01-01

    A new series of luminescent cyclometalated iridium(III) bipyridine estradiol conjugates [Ir(N-C)2(N-N)](PF6) (N-N = 5-(4-(17alpha-ethynylestradiolyl)phenyl)-2,2'-bipyridine, bpy-est, HN-C = 2-phenylpyridine, Hppy (1 a), 1-phenylpyrazole, Hppz (2 a), 7,8-benzoquinoline, Hbzq (3 a), 2-phenylquinoline, Hpq (4 a), 2-((1,1'-biphenyl)-4-yl)benzothiazole, Hbsb (5 a); N-N = 4-(N-(6-(4-(17alpha-ethynylestradiolyl)benzoylamino)hexyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine, bpy-C6-est, HN-C = Hppy (1 b), Hppz (2 b), Hbzq (3 b), Hpq (4 b), Hbsb (5 b)) was synthesized, characterized, and their photophysical and electrochemical properties studied. Upon photoexcitation, all the complexes displayed intense and long-lived emission in fluid solutions at 298 K and in low-temperature glass. The emission of complexes 1 a-3 a and 1 b-3 b was assigned to a triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir)-->pi*(bpy-est and N-C-)) state mixed with some triplet intraligand ((3)IL) (pi-->pi*) (N-C- and N-N) character. However, the emissive states of the pq- and bsb- complexes 4 a, 4 b, 5 a, and 5 b showed substantial (3)IL (pi-->pi*) (pq-/bsb-) character. The lipophilicity of all the complexes was determined by reversed-phase HPLC. Upon binding to estrogen receptor alpha, all of these iridium(III) estradiol conjugates exhibited emission enhancement and lifetime extension, rendering them a novel series of luminescent probes for this receptor.

  6. The synthesis of amphipathic prodrugs of 1,2-diol drugs with saccharide conjugates by high regioselective enzymatic protocol.

    Science.gov (United States)

    Quan, Jing; Chen, Zhichun; Han, Chengyou; Lin, Xianfu

    2007-02-15

    A facile, high regioselective enzymatic synthesis approach for the preparation of amphipathic prodrugs with saccharides of mephenesin and chlorphenesin was developed. Firstly, transesterification of two drugs with divinyl dicarboxylates with different carbon chain length was performed under the catalysis of Candida antarctica lipase acrylic resin and Lipozyme in anhydrous acetone at 50 degrees C, respectively. A series of lipophilic derivatives with vinyl groups of mephenesin and chlorphenesin were prepared. The influences of different organic solvents, enzyme sources, reaction time, and the acylation reagents on the synthesis of vinyl esters were investigated. And then, protease-catalyzed high regioselective acylation of D-glucose and D-mannose with vinyl esters of mephenesin and chlorphenesin gave drug-saccharide derivatives in good yields. The studies of lipophilicity and hydrolysis in vitro of prodrugs verified that drug-saccharide derivatives had amphipathic properties, and both lipophilic and amphipathic drug derivatives had obvious controlled release characteristics.

  7. A Synthesis of 6-(2,5-Dimethoxy-4-(2-aminopropylphenyl-hexylthiol. A Ligand for Conjugation with Fluorescent Cadmium Selenide/Zinc Sulfide Core/Shell Nanocrystals and Biological Imaging

    Directory of Open Access Journals (Sweden)

    Sandra J. Rosenthal

    2002-11-01

    Full Text Available The synthesis of 6-(2,5-dimethoxy-4-(2-aminopropylphenylhexylthiol, an agonist with a very high affinity for the 5HT2A serotonin receptor subtype is reported. This agonist was designed to be attached to highly fluorescent cadmium selenide/zinc sulfide core/shells via a thiol at the end of a linker arm. This conjugate has applications in biological assays and biological imaging.

  8. A Synthesis of 6-(2,5-Dimethoxy-4-(2-aminopropyl)phenyl)-hexylthiol. A Ligand for Conjugation with Fluorescent Cadmium Selenide/Zinc Sulfide Core/Shell Nanocrystals and Biological Imaging

    OpenAIRE

    Tomlinson, Ian D.; Grey, Jesse L.; Rosenthal, Sandra J.

    2002-01-01

    The synthesis of 6-(2,5-dimethoxy-4-(2-aminopropyl)phenyl)hexylthiol, an agonist with a very high affinity for the 5HT2A serotonin receptor subtype is reported. This agonist was designed to be attached to highly fluorescent cadmium selenide/zinc sulfide core/shells via a thiol at the end of a linker arm. This conjugate has applications in biological assays and biological imaging.

  9. New two-step synthesis of N-(2-ethylhexyl)-2,7-diiodocarbazole as a monomer for conjugated polymers

    Czech Academy of Sciences Publication Activity Database

    Výprachtický, Drahomír; Kmínek, Ivan; Pokorná, Veronika; Kaňková, Dana; Cimrová, Věra

    2013-01-01

    Roč. 16, č. 1 (2013), s. 31-37 ISSN 1385-772X R&D Projects: GA MŠk(CZ) 1M06031; GA ČR GAP106/12/0827 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : monomer synthesis * carbazole * ring closure Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.210, year: 2013

  10. Conjugal violence

    Directory of Open Access Journals (Sweden)

    Simona Mihaiu

    2015-10-01

    Full Text Available Scientific knowledge of different aspects related to conjugal violence is highly important for people directly involved, such as researchers, practitioners and the entire society. In this respect, globally, specialised studies continue to advance, offer correct definitions, clear descriptions, convincing assessments to certain issues, encouraging thus long-term research, since some specialists have managed to overcome restrictive or ideological methods and explanations. Moreover, in practice, debates reach almost all social, political and legal dimensions regarding appropriate and efficient forms of preventing conjugal violence. Unfortunately, in Romania there are fewer research and prevention approaches of this social problem. In general, attention is directed to domestic violence and conjugal violence is dealt with only implicitly. Considering the given context, the aim of the paper is to outline, by analysing specialised literature, a new research direction and implicitly, social intervention. I specify that this article represents a stage in the ongoing postdoctoral research project, entitled "Conjugal homicide. Aggressors and victims".

  11. Highly selective synthesis of conjugated dienoic and trienoic esters via alkyne elementometalation–Pd-catalyzed cross-coupling

    Science.gov (United States)

    Wang, Guangwei; Mohan, Swathi; Negishi, Ei-ichi

    2011-01-01

    All four stereoisomers (7–10) of ethyl undeca-2,4-dienoate were prepared in ≥98% isomeric purity by Pd-catalyzed alkenylation (Negishi coupling) using ethyl (E)- and (Z)-β-bromoacrylates. Although the stereoisomeric purity of the 2Z,4E-isomer (8) prepared by Suzuki coupling using conventional alkoxide and carbonate bases was ≤ 95%, as reported earlier, the use of CsF or nBu4NF as a promoter base has now been found to give all of 7–10 in ≥98% selectivity. Other widely known methods reveal considerable limitations. Heck alkenylation was satisfactory for the syntheses of the 2E,4E and 2E,4Z isomers of ≥98% purity, but the purity of the 2Z,4E isomer was ≤ 95%. Mutually complementary Horner–Wadsworth–Emmons and Still–Gennari (SG) olefinations are also of considerably limited scopes. Neither 2E,4Z nor 2Z,4Z isomer is readily prepared in ≥90% selectivity. In addition to (2Z,4E)-dienoic esters, some (2Z,4E,6E)- and (2Z,4E,6Z)-trienoic esters have been prepared in ≥98% selectivity by a newly devised Pd-catalyzed alkenylation–SG olefination tandem process. As models for conjugated higher oligoenoic esters, all eight stereoisomers for ethyl trideca-2,4,6-trienoate (23–30) have been prepared in ≥98% overall selectivity. PMID:21709262

  12. Synthesis of novel naphthoquinone-spermidine conjugates and their effects on DNA-topoisomerases I and II-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Andrea S.; Lima, Edson L.S.; Pinto, Angelo C.; Esteves-Souza, Andressa; Torrese, Jose C. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Quimica; Echevarria, Aurea [Universidade Federal Rural do Rio de Janeiro, RJ (Brazil). Dept. de Quimica; Camara, Celso A. [Paraiba Univ., Joao Pessoa, PB (Brazil). Lab. de Tecnologia Farmaceutica; Vargas, Maria D. [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Inst. de Quimica]. E-mail: mdvargas@vm.uff.br

    2006-05-15

    Novel derivatives of lapachol 2, nor-lapachol 3 and lawsone 4 have been synthesized by nucleophilic displacement of the methoxynaphthoquinones 2a, 3a and 4a with the polyamine (PA) N{sup 1}-Boc-N{sup 5}-Bn-spermidine 1a. The respective products 2b-4b were obtained in good yields and characterized by spectroscopic and analytical methods. The inhibitory action of these naphthoquinone-PA conjugates on DNA-topoisomerases (topo) I and II-{alpha} was evaluated by relaxation assay of supercoiled DNA plasmid. All compounds (1a 2b, 3b and 4b) presented significant inhibition of topo II-{alpha} catalytic activity at the 2 {mu}M dose. Considering that only PA 1a did not inhibit the enzyme catalytic activity at the 0.2 {mu}M dose, the appended naphthoquinone moiety acts as a 'value added' fragment. Compounds 1a 2b, 3b and 4b did not inhibit the enzyme DNA-topo I at the 200 {mu}M dose. (author)

  13. Synthesis of novel naphthoquinone-spermidine conjugates and their effects on DNA-topoisomerases I and II-alpha

    Directory of Open Access Journals (Sweden)

    Cunha Andréa S.

    2006-01-01

    Full Text Available Novel derivatives of lapachol 2, nor-lapachol 3 and lawsone 4 have been synthesized by nucleophilic displacement of the methoxynaphthoquinones 2a, 3a and 4a with the polyamine (PA N¹-Boc-N5-Bn-spermidine 1a. The respective products 2b-4b were obtained in good yields and characterized by spectroscopic and analytical methods. The inhibitory action of these naphthoquinone-PA conjugates on DNA-topoisomerases (topo I and II-alpha was evaluated by relaxation assay of supercoiled DNA plasmid. All compounds (1a 2b, 3b and 4b presented significant inhibition of topo II-alpha catalytic activity at the 2 µM dose. Considering that only PA 1a did not inhibit the enzyme catalytic activity at the 0.2 µM dose, the appended naphthoquinone moiety acts as a "value added" fragment. Compounds 1a 2b, 3b and 4b did not inhibit the enzyme DNA-topo I at the 200 µM dose.

  14. Synthesis, Chemosensory Properties, and Self-Assembly of Terpyridine-Containing Conjugated Polycarbazole through RAFT Polymerization and Heck Coupling Reaction

    Directory of Open Access Journals (Sweden)

    Po-Chih Yang

    2017-09-01

    Full Text Available We report the responsive fluorescence chemosensory phenomena of a carbazole-functionalized crosslinked polymer (PCaT with pendent terpyridine (tpy groups as receptors of metal ions. The polymer was synthesized using Heck polymerization between 3,6-dibromide groups in a carbazole-based polymer (PC2Br and divinyl tpy monomer. The effects of the polymeric structure on the optical and chemosensory properties of the PCaT were compared with those of a carbazole-tpy alternating conjugated polymer (PCT. Photoluminescence titrations demonstrated that the PCaT and PCT had the high sensing ability toward Fe3+ ions, with Stern–Volmer constants of 8.10 × 104 and 6.68 × 104 M−1, respectively. The limit of detection (LOD toward Fe3+ of the PCaT and PCT was estimated to be 1.31 × 10−6 and 1.81 × 10−6 M, respectively, and the superior LOD of the PCaT was ascribed to its lowly crosslinked structure. The fluorescence of the solutions of these polymers that were quenched by Fe3+ ions recovered when trace CN− anions were added because of the high stability constant of the CN−–Fe3+ complex. Micellar aggregates with a mean diameter of approximately 239.5 nm were formed by dissolving the PCaT in tetrahydrofuran (THF solution. Our results suggest that the PCaT is a promising material for chemosensory applications.

  15. Tandem catalysis in domino olefin cross-metathesis/intramolecular oxa-conjugate cyclization: concise synthesis of 2,6-cis-substituted tetrahydropyran derivatives.

    Science.gov (United States)

    Fuwa, Haruhiko; Noguchi, Takuma; Noto, Kenkichi; Sasaki, Makoto

    2012-10-28

    Herein, we describe the concise synthesis of 2,6-cis-substituted tetrahydropyran derivatives based on a domino olefin cross-metathesis/intramolecular oxa-conjugate cyclization (CM/IOCC) reaction. We have found that the domino CM/IOCC of δ-hydroxy olefins with α,β-unsaturated carbonyl compounds (e.g., trans-crotonaldehyde or N-acryloyl-2,5-dimethylpyrrole) could be efficiently achieved in the presence of the second-generation Hoveyda-Grubbs catalyst under elevated temperature conditions, directly affording 2,6-cis-substituted tetrahydropyrans in excellent yields with synthetically useful diastereoselectivity ("auto-tandem catalysis"). In addition, we have found that the domino CM/IOCC of δ-hydroxy olefins with α,β-unsaturated carbonyl compounds could be achieved simply by performing CM in the presence of a Brønsted acid in CH(2)Cl(2) at 25-35 °C, which delivered 2,6-cis-substituted tetrahydropyrans in good yields with excellent diastereoselectivity ("orthogonal-tandem catalysis"). To understand the mechanism of auto-tandem catalysis in the domino CM/IOCC reaction, we have investigated the role of ruthenium hydride complexes in the IOCC of a ζ-hydroxy α,β-unsaturated ketone as a model case.

  16. Quinazoline antifolates inhibiting thymidylate synthase: synthesis of four oligo(L-gamma-glutamyl) conjugates of N10-propargyl-5,8-dideazafolic acid and their enzyme inhibition.

    Science.gov (United States)

    Pawelczak, K; Jones, T R; Kempny, M; Jackman, A L; Newell, D R; Krzyzanowski, L; Rzeszotarska, B

    1989-01-01

    The synthesis is described of four oligo(gamma-glutamyl) conjugates of N10-propargyl-5,8-dideazafolic acid containing a total of two, three, four, and five L-glutamic acid residues. The tert-butyl group was chosen as the carboxyl protecting group in order to obviate the use of alkali and thus the possibility of gamma----alpha transpeptidation. The starting material, di-tert-butyl glutamate, was coupled to N-(benzyloxycarbonyl)-L-glutamic acid alpha-tert-butyl ester via a mixed anhydride with isobutyl chloroformate. Hydrogenolysis of the benzyloxycarbonyl group in the product gave a carboxyl-protected diglutamate, which either was acylated with 4-[(benzyloxycarbonyl)amino] benzoyl chloride to give a protected aminobenzamide or was cycled further by using the above mixed anhydride/hydrogenolysis sequence into tri-, tetra-, and pentaglutamates. Each of the last named was also acylated, as above, to give a benzamide. The benzyloxycarbonyl group in the benzamides was removed by hydrogenolysis and the amino groups thus exposed were N-alkylated with propargyl bromide. The resulting proparglyamines were further alkylated with 2-amino-6-(bromomethyl)-4-hydroxyquinazoline hydrobromide to give the antifolate poly(t-Bu) esters. Deprotection with trifluoroacetic acid in the final step delivered the desired antifolates as their trifluoroacetate salts. The di- to pentaglutamates were, respectively, 31-, 97-, 171-, and 167-fold more inhibitory to WI-L2 human thymidylate synthase than the parent compound.

  17. Bio-Conjugates for Nanoscale Applications

    DEFF Research Database (Denmark)

    Villadsen, Klaus

    Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives. Lipidated...

  18. CONJUGATED BLOCK-COPOLYMERS FOR ELECTROLUMINESCENT DIODES

    NARCIS (Netherlands)

    Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G

    In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence

  19. Design of a novel theranostic nanomedicine: synthesis and physicochemical properties of a biocompatible polyphosphazene–platinum(II conjugate

    Directory of Open Access Journals (Sweden)

    Avaji PG

    2016-03-01

    Full Text Available Prakash G Avaji,1,2,* Jung Hyun Park,1,* Hyun Jeong Lee,1 Yong Joo Jun,2 Kyung Su Park,3 Kyung Eun Lee,3 Soo-Jin Choi,4 Hwa Jeong Lee,1 Youn Soo Sohn2 1Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea; 2C & Pharm, Ewha Womans University, Seoul, Republic of Korea; 3Advanced Analysis Center, Korea Institute of Science and Technology, Seoul, Republic of Korea; 4Department of Food Science and Technology, Seoul Women’s University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: To develop a theranostic nanomedicine involving the antitumor-active moiety (dachPt(II (dach: trans-(±-1,2-diaminocyclohexane of oxaliplatin (OX, a new biocompatible polyphosphazene carrier polymer was designed by grafting with a methoxy poly(ethylene glycol (MPEG to increase duration of circulation in the blood and with aminoethanol (AE as a spacer group. The antitumor (dachPt moiety was conjugated to the carrier polymer using cis-aconitic acid (AA as a linker, resulting in a polymer conjugate formulated as [NP(MPEG550(AE-AAPt(dach]n, named “Polyplatin” (PP. PP was found to self-assemble into very stable polymeric nanoparticles with a mean diameter of 55.1 nm and a critical aggregation concentration of 18.5 mg/L in saline. PP could easily be labeled with a fluorescence dye such as Cy5.5 for imaging studies. The time-dependent ex vivo image studies on organ distributions and clearance of Cy-labeled PP have shown that PP accumulated in the tumor with high selectivity by the enhanced permeability and retention effect but was cleared out from all the major organs including the liver in about 4 weeks postinjection. Another time-dependent bioimaging study on distribution and clearance of PP in mouse kidney using laser ablation inductively coupled plasma mass spectroscopy has shown that PP accumulates much less in kidney and is more rapidly excreted than monomeric OX, which is in accord with the

  20. Synthesis and formulation of methotrexate (MTX) conjugated LaF3:Tb(3+)/chitosan nanoparticles for targeted drug delivery applications.

    Science.gov (United States)

    Mangaiyarkarasi, Rajendiran; Chinnathambi, Shanmugavel; Aruna, Prakasarao; Ganesan, Singaravelu

    2015-02-01

    Chitosan functionalized luminescent rare earth doped terbium nanoparticles (LaF3:Tb(3+)/chi NPs) as a drug carrier for methotrexate (MTX) was designed using a simple chemical precipitation method. The synthesized chitosan functionalized nanoparticles were found to be spherical in shape with an average diameter of 10-12nm. They are water soluble and biocompatible, in which the hydroxyl and amino functional groups on its surface are utilized for the bioconjugation of the anticancer drug, the methotrexate. The nature of MTX binding with LaF3:Tb(3+)/chi nanoparticles were examined using X-ray diffraction, zeta potential analyzer and transmission electron microscopy. The other interactions due to complex formation between MTX and LaF3:Tb(3+)/chi NPs were carried out by UV-Visible, steady and excited state fluorescence spectroscopy. The photo-physical characterization revealed that the adsorption and release of MTX from LaF3:Tb(3+)/chi NPs is faster than gold nanoparticles and also confirms that this may be due to weak interaction i.e. the Vander Waals force of attraction between the carboxyl and amino group of drug and nanoparticles. The maximum percentage yield and entrapment efficiency of 85.91±0.71 and 83.82± 0.14 were achieved at a stochiometric ratio of 4:5 of MTX and LaF3:Tb(3+)/chi nanoparticles respectively. In addition, antitumoral activity study reveals that MTX conjugated LaF3:Tb(3+)/chi nanoparticles show higher cytotoxic effect on MCF-7 breast cancer cell lines than that of free MTX. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Synthesis of zincphthalocyanine-based conjugated microporous polymers with rigid-linker as novel and green heterogeneous photocatalysts.

    Science.gov (United States)

    Cai, Lijun; Li, Yanwei; Li, Yanhui; Wang, Hengguo; Yu, Yang; Liu, Ying; Duan, Qian

    2018-04-15

    The novel zincphthalocyanine-based conjugated microporous polymers with rigid-linker (α-ZnPc-CMP and β-ZnPc-CMP) were synthesized by copolymerization of zinc phthalocyanine (ZnPc) and 4, 6-diaminoresorcinol dihydrochloride (DADHC). The α-ZnPc-CMP and β-ZnPc-CMP were utilized as heterogeneous photocatalysts to degrade Rhodamine B (RhB) in aqueous solution. It is the first time for MPc-based CMPs used as heterogeneous photocatalysts for photodegradation of RhB to date. The highly ordered skeletal alignment and two-dimensional open-channel structure of α-ZnPc-CMP and β-ZnPc-CMP not only solve the aggregation of ZnPc and enhance its photocatalytic activity, but also facilitate the recycling and avoid the secondary pollution. The chemical structures and morphologies of α-ZnPc-CMP and β-ZnPc-CMP were well characterized by Fourier transform infrared spectra (FT-IR), solid-state 13 C nuclear magnetic resonance ( 13 C NMR), scanning electron microscopy (SEM), N 2 -sorption/ desorption and X-ray diffraction (XRD). The solubility experiments and thermogravimetric analysis (TGA) showed they have good chemical stability and recyclability. Furthermore, the photocatalytic tests indicated α-ZnPc-CMP and β-ZnPc-CMP have excellent photocatalytic performances for degradation of RhB (3 h, degraded 98 and 97.47%) in the presence of H 2 O 2 under visible-light irradiation. All results reveal that α-ZnPc-CMP and β-ZnPc-CMP have great potential as photocatalysts on the degradation of organic dye contaminants. Moreover, the possible reaction mechanism of α-ZnPc-CMP and β-ZnPc-CMP as photocatalysts for the degradation of RhB is proposed. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Glutathione Conjugation

    Science.gov (United States)

    Shimabukuro, R. H.; Frear, D. S.; Swanson, H. R.; Walsh, W. C.

    1971-01-01

    The primary factor for atrazine selectivity in corn (Zea mays) is the activity of a soluble enzyme, glutathione S-transferase, which detoxifies atrazine by catalyzing the formation of an atrazine-glutathione conjugate (GS-atrazine). The nonenzymatic, benzoxazinone-catalyzed hydrolysis of atrazine to hydroxyatrazine contributed to the total resistance of corn to atrazine, but the nonenzymatic detoxication pathway does not seem to be essential for resistance. All corn lines investigated, except for susceptible GT112, rapidly detoxified atrazine by glutathione conjugation. Only GT112 had low glutathione S-transferase activity. Hydroxyatrazine was found in significant quantities only when atrazine was introduced initially into the roots. The amount of hydroxyatrazine formed was nearly equal for susceptible GT112 and most of the resistant corn lines investigated. This investigation indicates that some plants protect themselves against toxic organic halide compounds with a mechanism similar to that known to exist in animals. PMID:5543779

  3. Cascade Polymerization via Controlled Tandem Olefin Metathesis/Metallotropic 1,3-Shift Reactions for the Synthesis of Fully Conjugated Polyenynes.

    Science.gov (United States)

    Kang, Cheol; Park, Hyeon; Lee, Jin-Kyung; Choi, Tae-Lim

    2017-08-23

    We demonstrate the first example of cascade polymerization by combining olefin metathesis and metallotropic 1,3-shift reactions to form unique conjugated polyenynes. Rational design of monomers enabled controlled polymerization, and kinetic investigation of the polymerization mechanism was conducted.

  4. Design, Synthesis and Characterization of Functionalized Poly (p-Phenylene Vinylene) Copolymers: The Development of a Universal Method towards Advanced Conjugated Polymers for Device Applications

    OpenAIRE

    Duchateau, Jan

    2009-01-01

    n Chapter 1, a general introduction to the field of conjugated polymers is given. Conjugated polymers are unique materials, which combine the electronic and optical properties of semiconductors with the mechanical properties and processability of conventional polymers. Generally, organic and polymeric materials have the advantage of being lightweight, flexible, low-cost and straightforward to process. Nowadays, as a result of the wide variety in available synthetic methods, it is possible to ...

  5. Synthesis and Evaluation of a Series of Long-Acting Glucagon-Like Peptide-1 (GLP-1) Pentasaccharide Conjugates for the Treatment of Type 2 Diabetes.

    Science.gov (United States)

    Irwin, Nigel; Patterson, Steven; de Kort, Martin; Moffett, R Charlotte; Wisse, Jeffry A J; Dokter, Wim H A; Bos, Ebo S; Miltenburg, André M M; Flatt, Peter R

    2015-08-01

    The present study details the development of a family of novel D-Ala(8) glucagon-like peptide-1 (GLP-1) peptide conjugates by site specific conjugation to an antithrombin III (ATIII) binding carrier pentasaccharide through tetraethylene glycol linkers. All conjugates were found to possess potent insulin-releasing activity. Peptides with short linkers (GLP-1 receptor (GLP-1-R) binding affinity. All D-Ala(8) GLP-1 conjugates exhibited prominent glucose-lowering action. Biological activity of the Lys(37) short-linker peptide was evident up to 72 h post-injection. In agreement, the pharmacokinetic profile of this conjugate (t1/2 , 11 h) was superior to that of the GLP-1-R agonist, exenatide. Once-daily injection of the Lys(37) short-linker peptide in ob/ob mice for 21 days significantly decreased food intake and improved HbA1c and glucose tolerance. Islet size was decreased, with no discernible change in islet number. The beneficial effects of the Lys(37) short-linker peptide were similar to or better than either exenatide or liraglutide, another GLP-1-R agonist. In conclusion, GLP-1 peptides conjugated to an ATIII binding carrier pentasaccharide have a substantially prolonged bioactive profile compatible for possible once-weekly treatment of type 2 diabetes in humans. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Synthesis of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates as microtubule targeting and apoptosis inducing agents.

    Science.gov (United States)

    Sultana, Faria; Reddy Bonam, Srinivasa; Reddy, V Ganga; Nayak, V Lakshma; Akunuri, Ravikumar; Rani Routhu, Sunitha; Alarifi, Abdullah; Halmuthur, M Sampath Kumar; Kamal, Ahmed

    2018-02-01

    A series of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates (5a-aa) were designed, synthesized and evaluated for their cytotoxic potency against a panel of human cancer cell lines like lung (A-549), breast (MDA MB-231), prostrate (DU-145) and colon cancer (HT-29). Preliminary results revealed that some of these conjugates like 5d and 5u exhibited significant antiproliferative effect against human breast cancer (MDA MB-231) with IC 50 values of 1.3 and 1.2 µM respectively. To investigate the mechanistic aspects underlying the activity, the detailed biological studies of these promising conjugates (5d and 5u) were carried out on the MDA MB-231 cancer cells. Flow cytometric analysis revealed that these conjugates induce cell-cycle arrest in the G2/M phase. The tubulin polymerization assay suggests that these conjugates effectively inhibit microtubule assembly. In addition, morphological changes, reactive oxygen species (ROS) detection by 2', 7'-dichlorofluorescin diacetate (DCFDA) and annexin V-FITC/PI assays indicate that 5d and 5u induces apoptosis. Furthermore, in silico computational studies, including molecular docking studies have been carried out to rationalise the binding modes of these conjugates with the tubulin protein. Copyright © 2017. Published by Elsevier Inc.

  7. Oligonucleotides conjugated to short lysine chains.

    Science.gov (United States)

    Winkler, Johannes; Urban, Ernst; Noe, Christian R

    2005-01-01

    A new method for synthesizing oligonucleotide peptide conjugates by an in-line approach is presented. A phosphorothioate oligonucleotide with the sequence of bcl-2 targeted Oblimersen by employing a modified 2'-amino-2'-desoxy-uridine nucleotide bearing a succinyl linker at the 2' position was prepared. The carboxyl group was protected for solid-phase synthesis as the benzyl ester. Ester cleavage was afforded by a phase transfer reaction using palladium nanoparticles as catalyst and cyclohexadiene as hydrogen donor. Short tails of up to three lysyl residues were conjugated to the oligonucleotide by an inverse stepwise peptide synthesis. The conjugates were characterized by HPLC, mass spectrometry, and circular dichroism. Influence of lysyl tails on CD spectra were minimal. Melting profiles revealed only minimal destabilizing effects on duplexes by conjugation of peptides.

  8. Design and synthesis of 1,2,3-triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates as tubulin polymerization inhibitors.

    Science.gov (United States)

    Shaik, Siddiq Pasha; Vishnuvardhan, M V P S; Sultana, Faria; Subba Rao, A V; Bagul, Chandrakant; Bhattacharjee, Debanjan; Kapure, Jeevak Sopanrao; Jain, Nishant; Kamal, Ahmed

    2017-07-01

    1,2,3-Triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates (5a-v) were designed, synthesized and evaluated for their cytotoxic potency against some human cancer cell lines like DU-145 (prostate), HeLa (cervical), MCF-7 (breast) HepG2 (liver) and A549 (lung). Preliminary results revealed that some of these conjugates like 5f and 5k exhibited significant antiproliferative effect against human breast cancer cells (MCF-7) with IC 50 values of 0.60 and 0.78µM respectively. Flow cytometric analysis of the cell cycle demonstrated an increase in the percentage of cells in the G 2 /M phase which was further authenticated by elevation of cyclin B1 protein levels. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 5f and 5k, and western blot analysis revealed that these conjugates accumulated more tubulin in the soluble fraction. Moreover, the conjugates caused apoptosis of the cells that was confirmed by mitochondrial membrane potential and Annexin V-FITC assay. Molecular docking studies indicated that these conjugates occupy the colchicine binding site of the tubulin protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Hepatobiliary delivery of polyaminopolycarboxylate chelates: Synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate

    Energy Technology Data Exchange (ETDEWEB)

    Betebenner, D.A.; Carney, P.L.; Zimmer, A.M.; Kazikiewicz, J.M.; Bruecher, E.S.; Sherry, A.D.; Johnson, D.K. (Abbott Laboratories, Abbott Park, Illinois (USA))

    1991-03-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance.

  10. Making Ends Meet: Flow Synthesis as the Answer to Reproducible High-Performance Conjugated Polymers on the Scale that Roll-to-Roll Processing Demands

    DEFF Research Database (Denmark)

    Helgesen, Martin; Carlé, Jon Eggert; Benatto, Gisele Alves dos Reis

    2015-01-01

    synthesis. Upscaling from 300 mg batch synthesis to 10 g flow synthesis affords PBDTTTz-4 with a production rate of up to 120 g day −1 for a very simple in-house build flow reactor. An average power conversion efficiency (PCE) of 3.5% is achieved on a small scale (1 cm 2 ) and an average PCE of 3...

  11. Synthesis and characterization of Her2-NLP peptide conjugates targeting circulating breast cancer cells: cellular uptake and localization by fluorescent microscopic imaging.

    Science.gov (United States)

    Cai, Huawei; Singh, Ajay N; Sun, Xiankai; Peng, Fangyu

    2015-01-01

    To synthesize a fluorescent Her2-NLP peptide conjugate consisting of Her2/neu targeting peptide and nuclear localization sequence peptide (NLP) and assess its cellular uptake and intracellular localization for radionuclide cancer therapy targeting Her2/neu-positive circulating breast cancer cells (CBCC). Fluorescent Cy5.5 Her2-NLP peptide conjugate was synthesized by coupling a bivalent peptide sequence, which consisted of a Her2-binding peptide (NH2-GSGKCCYSL) and an NLP peptide (CGYGPKKKRKVGG) linked by a polyethylene glycol (PEG) chain with 6 repeating units, with an activated Cy5.5 ester. The conjugate was separated and purified by HPLC and then characterized by Maldi-MS. The intracellular localization of fluorescent Cy5.5 Her2-NLP peptide conjugate was assessed by fluorescent microscopic imaging using a confocal microscope after incubation of Cy5.5-Her2-NLP with Her2/neu positive breast cancer cells and Her2/neu negative control breast cancer cells, respectively. Fluorescent signals were detected in cytoplasm of Her2/neu positive breast cancer cells (SKBR-3 and BT474 cell lines), but not or little in cytoplasm of Her2/neu negative breast cancer cells (MDA-MB-231), after incubation of the breast cancer cells with Cy5.5-Her2-NLP conjugates in vitro. No fluorescent signals were detected within the nuclei of Her2/neu positive SKBR-3 and BT474 breast cancer cells, neither Her2/neu negative MDA-MB-231 cells, incubated with the Cy5.5-Her2-NLP peptide conjugates, suggesting poor nuclear localization of the Cy5.5-Her2-NLP conjugates localized within the cytoplasm after their cellular uptake and internalization by the Her2/neu positive breast cancer cells. Her2-binding peptide (KCCYSL) is a promising agent for radionuclide therapy of Her2/neu positive breast cancer using a β(-) or α emitting radionuclide, but poor nuclear localization of the Her2-NLP peptide conjugates may limit its use for eradication of Her2/neu-positive CBCC using I-125 or other Auger electron

  12. Facile synthesis of a conjugation-grafted-TiO2 nanohybrid with enhanced visible-light photocatalytic properties from nanotube titanic acid precursors

    Science.gov (United States)

    Guo, Yanru; Zhang, Min; Zhang, Zhihua; Li, Qiuye; Yang, Jianjun

    2016-08-01

    A conjugation-grafted-TiO2 nanohybrid was synthesized by chemically grafting conjugated structures on the surface of nanotube titanic acid (NTA) precursor-based TiO2 through the controlled thermal degradation of a coacervated polymer layer of polyvinyl alcohol (PVA). The interfacial interactions between the NTA precursor-based TiO2 and conjugated structures were characterized using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Moreover, the effects of the NTA's pretreatment temperature and the weight ratio of NTA to PVA on the photocatalytic degradation of methyl orange were also investigated. A higher NTA pretreatment temperature and a lower NTA to PVA weight ratio were found to enhance photogenerated electron-hole separation efficiency and photocatalytic activity. Moreover, the conjugation-grafted-TiO2 nanohybrid synthesized from the NTA precursor displayed a much higher visible-light photocatalytic activity than that of the sample obtained from the P25 precursor. The origin of the enhanced photocatalytic activity under visible-light irradiation is also discussed in detail.

  13. Synthesis of Poly[APMA]-DOTA-64Cu Conjugates for Interventional Radionuclide Therapy of Prostate Cancer: Assessment of Intratumoral Retention by Micro–Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    Jianchao Yuan

    2007-01-01

    Full Text Available To develop new radiopharmaceuticals for interventional radionuclide therapy of locally recurrent prostate cancer, poly[N-(3-aminopropylmethacrylamide] [poly(APMA] polymers were synthesized by free radical precipitation polymerization in acetonedimethylsulfoxide using N,N‘-azobis(isobutyronitrile as the initiator. The polymers were characterized with nuclear magnetic resonance, size exclusion chromatography, and dynamic light scattering (Mn 5 2.40 × 104, Mw/Mn = 1.87. Subsequently, poly[APMA] was coupled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA using 1-(3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride as an activator, followed by conjugation with 64Cu radionuclide. Prolonged retention of poly[APMA]-DOTA-64Cu conjugates within the tumor tissues was demonstrated by micro–positron emission tomography at 24 hours following intra-tumoral injection of the conjugates to human prostate xenografts in mice. The data suggest that the poly[APMA]-DOTA-64Cu conjugates might be useful for interventional radionuclide therapy of locally recurrent prostate cancer in humans.

  14. Conjugated Polymers Containing BODIPY and Fluorene Units for Sensitive Detection of CN− Ions: Site-Selective Synthesis, Photo-Physical and Electrochemical Properties

    Directory of Open Access Journals (Sweden)

    Tian He

    2017-10-01

    Full Text Available Conjugated polymers containing distinct molecular units are expected to be very interesting because of their unique properties endowed by these units and the formed conjugated polymers. Herein, four new conjugated copolymers based on fluorene and 4,4’-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY have been designed and synthesized via Sonogashira polymerization. The fluorene unit was attached to the 3,5- or 2,6-positions of BODIPY by ethynylenes or p-diacetylenebenzene. The obtained polymers show good thermal stability and broad absorption in the wavelength range from 300 to 750 nm. The effects of site-selective copolymerization and conjugation length along the polymer backbone on the optoelectronic and electrochemical properties of these copolymers were systematically studied by UV-Vis spectroscopy, photoluminescence (PL and cyclic voltammetry. Besides, it is found that the BODIPY-based copolymers exhibit selectively sensitive responses to cyanide anions, resulting in obvious change of UV-Vis absorption spectra and significant fluorescence quenching of the polymers among various common anions.

  15. Facile synthesis of a conjugation-grafted-TiO{sub 2} nanohybrid with enhanced visible-light photocatalytic properties from nanotube titanic acid precursors

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yanru; Zhang, Min, E-mail: zm1012@henu.edu.cn; Zhang, Zhihua; Li, Qiuye; Yang, Jianjun [Henan University, National and Local Joint Engineering Research Center for Applied Technology of Hybrid Nanomaterials (China)

    2016-08-15

    A conjugation-grafted-TiO{sub 2} nanohybrid was synthesized by chemically grafting conjugated structures on the surface of nanotube titanic acid (NTA) precursor-based TiO{sub 2} through the controlled thermal degradation of a coacervated polymer layer of polyvinyl alcohol (PVA). The interfacial interactions between the NTA precursor-based TiO{sub 2} and conjugated structures were characterized using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Moreover, the effects of the NTA’s pretreatment temperature and the weight ratio of NTA to PVA on the photocatalytic degradation of methyl orange were also investigated. A higher NTA pretreatment temperature and a lower NTA to PVA weight ratio were found to enhance photogenerated electron–hole separation efficiency and photocatalytic activity. Moreover, the conjugation-grafted-TiO{sub 2} nanohybrid synthesized from the NTA precursor displayed a much higher visible-light photocatalytic activity than that of the sample obtained from the P25 precursor. The origin of the enhanced photocatalytic activity under visible-light irradiation is also discussed in detail.

  16. The synthesis of taurine-conjugated bile acids and bile acid sulfates labeled with 14C or 3H in the taurine moiety

    International Nuclear Information System (INIS)

    Jie Zhang; Griffiths, W.J.; Sjoevall, Jan

    1997-01-01

    Studies of bile acid transport systems require radio-labeled taurine-conjugated bile acids with high specific activity. An established procedure was optimized to provide mild, fast, and effective conjugation of radio-labeled taurine with different types of bile acids, including those with labile 7α-hydroxy-3-oxo-Δ 4 or 3β, 7α-dihydroxy-Δ 5 structures. Taurine labeled with 14 C or 3 H was reacted with excess bile acid anhydride formed from the tributylamine salt and ethylchloroformate (2/1 M/M) in aqueous dioxane for 15 min at room temperature. The yields were higher than 95% and less than 2% side products were formed. Bile acid sulfates were conjugated with 14 C- or 3 H-labeled taurine by using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as the coupling reagent. The products were effectively purified by chromatography of the sodium salts on Sephadex LH-20. The yields of taurine-conjugated bile acid sulfates were 65-70%. (author)

  17. Remarkable phosphine-effect on the intramolecular aldol reactions of unsaturated 1,5-diketones: highly regioselective synthesis of cross-conjugated dienones.

    Science.gov (United States)

    Thalji, Reema K; Roush, William R

    2005-12-07

    We report a phosphine-mediated intramolecular aldol cyclization of unsaturated diketones that proceeds with extremely high levels of regioselectivity for the cross-conjugated bicyclic dienone products. The sense of regioselectivity observed in this reaction is complementary to that obtained using traditional aldol conditions. Experimental evidence that supports the involvement of a phosphine Michael adduct is described.

  18. Oligopyridine-ruthenium(II)-amino acid conjugates: synthesis, characterization, DNA binding properties and interactions with the oligonucleotide duplex d(5'-CGCGCG-3')2

    Czech Academy of Sciences Publication Activity Database

    Triantafillidi, K.; Karidi, K.; Malina, Jaroslav; Garoufis, A.

    -, č. 32 (2009), s. 6403-6415 ISSN 1477-9226 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : oligopyridine- ruthenium (II)-amino acid conjugates * diastereomeric DNA binding * DNA photocleavage Subject RIV: BO - Biophysics Impact factor: 4.081, year: 2009

  19. (+)-camphor-derived tri- and tetradentate amino alcohols; synthesis and application as ligands in the nickel catalyzed enantioselective conjugate addition of diethylzinc

    NARCIS (Netherlands)

    Vries, André H.M. de; Imbos, Rosalinde; Feringa, Bernard

    1997-01-01

    Several novel tri- and tetradentate amino alcohol ligands, all derived from (+)-camphor, have been synthesized by using specific N-alkylation procedures. The amino alcohols were employed as chiral ligands in the nickel catalyzed conjugate additions of diethylzine to chalcone and cyclohexenone as

  20. Synthesis of antifungal vaccines by conjugation of β-1,2 trimannosides with T-cell peptides and covalent anchoring of neoglycopeptide to tetanus toxoid.

    Science.gov (United States)

    Cartmell, Jonathan; Paszkiewicz, Eugenia; Dziadek, Sebastian; Tam, Pui-Hang; Luu, Thanh; Sarkar, Susmita; Lipinski, Tomasz; Bundle, David R

    2015-02-11

    Selective strategies for the construction of novel three component glycoconjugate vaccines presenting Candida albicans cell wall glycan (β-1,2 mannoside) and polypeptide fragments on a tetanus toxoid carrier are described. The first of two conjugation strategies employed peptides bearing an N-terminal thiopropionyl residue for conjugation to a trisaccharide equipped with an acrylate linker and a C-terminal S-acetyl thioglycolyl moiety for subsequent linking of neoglycopeptide to bromoacetylated tetanus toxoid. Michael addition of acrylate trisaccharides to peptide thiol under mildly basic conditions gave a mixture of N- and C- terminal glyco-peptide thioethers. An adaptation of this strategy coordinated S-acyl protection with anticipated thioester exchange equilibria. This furnished a single chemically defined fully synthetic neoglycopeptide conjugate that could be anchored to a tetanus toxoid carrier and avoids the introduction of exogenous antigenic groups. The second strategy retained the N-terminal thiopropionyl residue but replaced the C-terminal S-acetate functionality with an azido group that allowed efficient, selective formation of neoglycopeptide thioethers and subsequent conjugation of these with propargylated tetanus toxoid, but introduced potentially antigenic triazole linkages. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. A 2,5-Dihydroxybenzoic Acid–Gelatin Conjugate: The Synthesis, Antiviral Activity and Mechanism of Antiviral Action Against Two Alphaherpesviruses

    Science.gov (United States)

    Lisov, Alexander; Vrublevskaya, Veronika; Lisova, Zoy; Leontievsky, Alexey; Morenkov, Oleg

    2015-01-01

    Various natural and synthetic polyanionic polymers with different chemical structures are known to exhibit potent antiviral activity in vitro toward a variety of enveloped viruses and may be considered as promising therapeutic agents. A water-soluble conjugate of 2,5-dihydroxybezoic acid (2,5-DHBA) with gelatin was synthesized by laccase-catalyzed oxidation of 2,5-DHBA in the presence of gelatin, and its antiviral activity against pseudorabies virus (PRV) and bovine herpesvirus type 1 (BoHV-1), two members of the Alphaherpesvirinae subfamily, was studied. The conjugate produced no direct cytotoxic effect on cells, and did not inhibit cell growth at concentrations up to 1000 µg/mL. It exhibited potent antiviral activity against PRV (IC50, 1.5–15 µg/mL for different virus strains) and BoHV-1 (IC50, 0.5–0.7 µg/mL). When present during virus adsorption, the conjugate strongly inhibited the attachment of PRV and BoHV-1 to cells. The 2,5-DHBA–gelatin conjugate had no direct virucidal effect on the viruses and did not influence their penetration into cells, cell-to-cell spread, production of infectious virus particles in cells, and expression of PRV glycoproteins E and B. The results indicated that the 2,5-DHBA–gelatin conjugate strongly inhibits the adsorption of alphaherpesviruses to cells and can be a promising synthetic polymer for the development of antiviral formulations against alphaherpesvirus infections. PMID:26501311

  2. Conjugates of Superoxide Dismutase 1 with Amphiphilic Poly(2-oxazoline) Block Copolymers for Enhanced Brain Delivery: Synthesis, Characterization and Evaluation in Vitro and in Vivo

    KAUST Repository

    Tong, Jing

    2013-01-07

    Superoxide dismutase 1 (SOD1) efficiently catalyzes dismutation of superoxide, but its poor delivery to the target sites in the body, such as brain, hinders its use as a therapeutic agent for superoxide-associated disorders. Here to enhance the delivery of SOD1 across the blood-brain barrier (BBB) and in neurons the enzyme was conjugated with poly(2-oxazoline) (POx) block copolymers, P(MeOx-b-BuOx) or P(EtOx-b-BuOx), composed of (1) hydrophilic 2-methyl-2-oxazoline (MeOx) or 2-ethyl-2-oxazoline (EtOx) and (2) hydrophobic 2-butyl-2-oxazoline (BuOx) repeating units. The conjugates contained from 2 to 3 POx chains joining the protein amino groups via cleavable -(ss)- or noncleavable -(cc)- linkers at the BuOx block terminus. They retained 30% to 50% of initial SOD1 activity, were conformationally and thermally stable, and assembled in 8 or 20 nm aggregates in aqueous solution. They had little if any toxicity to CATH.a neurons and displayed enhanced uptake in these neurons as compared to native or PEGylated SOD1. Of the two conjugates, SOD1-(cc)-P(MeOx-b-BuOx) and SOD1-(cc)-P(EtOx-b-BuOx), compared, the latter was entering cells 4 to 7 times faster and at 6 h colocalized predominantly with endoplasmic reticulum (41 ± 3%) and mitochondria (21 ± 2%). Colocalization with endocytosis markers and pathway inhibition assays suggested that it was internalized through lipid raft/caveolae, also employed by the P(EtOx-b-BuOx) copolymer. The SOD activity in cell lysates and ability to attenuate angiotensin II (Ang II)-induced superoxide in live cells were increased for this conjugate compared to SOD1 and PEG-SOD1. Studies in mice showed that SOD1-POx had ca. 1.75 times longer half-life in blood than native SOD1 (28.4 vs 15.9 min) and after iv administration penetrated the BBB significantly faster than albumin to accumulate in brain parenchyma. The conjugate maintained high stability both in serum and in brain (77% vs 84% at 1 h postinjection). Its amount taken up by the brain

  3. Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

    Directory of Open Access Journals (Sweden)

    Manuel Johannes

    2015-01-01

    Full Text Available The development of selective anticancer vaccines that provide enhanced protection against tumor recurrence and metastasis has been the subject of intense research in the scientific community. The tumor-associated glycoprotein MUC1 represents a well-established target for cancer immunotherapy and has been used for the construction of various synthetic vaccine candidates. However, many of these vaccine prototypes suffer from an inherent low immunogenicity and are susceptible to rapid in vivo degradation. To overcome these drawbacks, novel fluorinated MUC1 glycopeptide-BSA/TTox conjugate vaccines have been prepared. Immunization of mice with the 4’F-TF-MUC1-TTox conjugate resulted in strong immune responses overriding the natural tolerance against MUC1 and producing selective IgG antibodies that are cross-reactive with native MUC1 epitopes on MCF-7 human cancer cells.

  4. Asymmetric Synthesis of exo-Isobrevicomin and exo-Brevicomin via Conjugated Addition of Primary Alkyl Iodides to a,b-Unsaturated Ketones

    Directory of Open Access Journals (Sweden)

    Sousa Andréa L. de

    2002-01-01

    Full Text Available (--exo-Isobrevicomin (1 and (+-exo-brevicomin (2 are volatile substances produced by males of the beetles Dendroctonus ponderosae, which inhabit pine trees found in the northern hemisphere, frequently causing the death of their host. In order to obtain these aggregation pheromones, which present the 6,8-dioxabicyclo[3.2.1]octane structure, the synthetic strategies utilized in this work had as key steps the Sharpless asymmetric dihydroxylation and the conjugated addition, promoted by the Zn(Cu couple in aqueous medium and accelerated by ultrasound. The conjugated addition of acetonides 13 and 14 to the respective unsaturated ketones (methyl vinyl ketone and ethyl vinyl ketone furnished the adducts 15 and 16. The intramolecular catalyzed cyclization of compounds 15 and 16 with phosphotungstic acid (H3PW12O40 produced exo-isobrevicomin (1 and exo-brevicomin (2.

  5. Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Adolph, Sidsel K.; Andresen, Thomas Lars

    2010-01-01

    The synthesis of two secretory phospholipase A(2) IIA sensitive 15-deoxy-Delta(12,14)-prostaglandin J(2) phospholipid conjugates is described and their biophysical and biological properties are reported. The conjugates spontaneously form particles in the liposome size region upon dispersion in an...

  6. Hyperbranched-dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency

    Science.gov (United States)

    Alavi, Seyyed Jamal; Gholami, Leila; Askarian, Saeedeh; Darroudi, Majid; Massoudi, Abdolhossein; Rezaee, Mehdi; Kazemi Oskuee, Reza

    2017-02-01

    The applications of dendrimer-based vectors seem to be promising in non-viral gene delivery because of their potential for addressing the problems with viral vectors. In this study, generation 3 poly(propyleneimine) (G3-PPI) dendrimers with 1, 4-diaminobutane as a core initiator was synthesized using a divergent growth approach. To increase the hydrophobicity and reduce toxicity, 10% of primary amines of G3-PPI dendrimers were replaced with bromoalkylcarboxylates with different chain lengths (6-bromohexanoic and 10-bromodecanoic). Then, to retain the overall buffering capacity and enhance transfection, the alkylcarboxylate-PPIs were conjugated to 10 kDa branched polyethylenimine (PEI). The results showed that the modified PPI was able to form complexes with the diameter of less than 60 nm with net-positive surface charge around 20 mV. No significant toxicity was observed in modified PPIs; however, the hexanoate conjugated PPI-PEI (PPI-HEX-10% PEI) and the decanoate conjugated PPI-PEI (PPI-DEC-10%-PEI) showed the best transfection efficiency in murine neuroblastoma (Neuro-2a) cell line, even PPI-HEX-10%-PEI showed transfection efficiency equal to standard PEI 25 kDa with reduced toxicity. This study suggested a new series of hyperbranched (PEI)-dendrimer (PPI) architectural copolymers as non-viral gene delivery vectors with high transfection efficiency and low toxicity.

  7. Shape-controlled synthesis of protein-conjugated CdS nanocrystals (NCs) and study on the binding of Cd2+/CdS to trypsin

    Science.gov (United States)

    Qin, Dezhi; Wang, Li; Wang, Yabo; Du, Xian; Zhang, Li; Zhang, Qiuxia; He, Bingyu

    2017-07-01

    Protein-conjugated CdS nanocrystals (NCs) with different morphology have been synthesized under biomimetic condition using trypsin as capping agent in aqueous medium. The reaction parameters including concentration of trypsin, pH value, reaction time, and temperature have a major influence on the morphology and optical property of CdS NCs. XRD, selected area electron diffraction (SAED), TEM, HRTEM, and EDS characterizations were used to investigate the structure, composition, morphology, and size of as-prepared products. The binding reaction between Cd2+/CdS and trypsin was investigated systematically through various spectroscopic methods. UV-vis, FT-IR, photoluminescence (PL) spectra, and conductivity analysis of Cd2+-trypsin suggest that Cd2+ ions could coordinate with the functional groups of trypsin and induce the formation of unfolding and loosening structure in protein molecules, and the change of protein conformation was also verified by circular dichroism (CD) spectra. This interaction increased local supersaturation of Cd2+ ions around the groups of trypsin and reduced the nucleation activation energy of CdS nuclei, which favored heterogeneous nucleation in trypsin matrix and resulted in the formation of inorganic-organic hybrid materials. The functional integrity of the enzyme conjugated to CdS NCs was studied by monitoring the enzymatic activity of CdS-trypsin conjugates. The fluorescence of CdS NCs is dependent strongly on trypsin which passivates the surface of NCs.

  8. Hyperbranched–dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Alavi, Seyyed Jamal [Ferdowsi University of Mashhad, Department of Chemistry, Faculty of Science (Iran, Islamic Republic of); Gholami, Leila [Mashhad University of Medical Sciences, Department of Modern Sciences and Technologies, School of Medicine (Iran, Islamic Republic of); Askarian, Saeedeh [Mashhad University of Medical Sciences, Department of Medical Biotechnology, School of Medicine (Iran, Islamic Republic of); Darroudi, Majid [Mashhad University of Medical Sciences, Nuclear Medicine Research Center (Iran, Islamic Republic of); Massoudi, Abdolhossein [University of Payam noor, Department of Chemistry (Iran, Islamic Republic of); Rezaee, Mehdi; Kazemi Oskuee, Reza, E-mail: Oskueekr@mums.ac.ir [Mashhad University of Medical Sciences, Department of Medical Biotechnology, School of Medicine (Iran, Islamic Republic of)

    2017-02-15

    The applications of dendrimer-based vectors seem to be promising in non-viral gene delivery because of their potential for addressing the problems with viral vectors. In this study, generation 3 poly(propyleneimine) (G3-PPI) dendrimers with 1, 4-diaminobutane as a core initiator was synthesized using a divergent growth approach. To increase the hydrophobicity and reduce toxicity, 10% of primary amines of G3-PPI dendrimers were replaced with bromoalkylcarboxylates with different chain lengths (6-bromohexanoic and 10-bromodecanoic). Then, to retain the overall buffering capacity and enhance transfection, the alkylcarboxylate–PPIs were conjugated to 10 kDa branched polyethylenimine (PEI). The results showed that the modified PPI was able to form complexes with the diameter of less than 60 nm with net-positive surface charge around 20 mV. No significant toxicity was observed in modified PPIs; however, the hexanoate conjugated PPI–PEI (PPI-HEX-10% PEI) and the decanoate conjugated PPI–PEI (PPI-DEC-10%-PEI) showed the best transfection efficiency in murine neuroblastoma (Neuro-2a) cell line, even PPI-HEX-10%-PEI showed transfection efficiency equal to standard PEI 25 kDa with reduced toxicity. This study suggested a new series of hyperbranched (PEI)–dendrimer (PPI) architectural copolymers as non-viral gene delivery vectors with high transfection efficiency and low toxicity.

  9. Synthesis, characterization and immunological properties of LPS-based conjugate vaccine composed of O-polysaccharide from pseudomonas aeruginosa IATS 10 bound to recombinant exoprotein A

    International Nuclear Information System (INIS)

    Abu-baker, N. F.; Masoud, H. A.; Jaber, B. M.

    2008-01-01

    Pseudomonas aeruginosa is an improtant opportunistic pathogen that can cause infection in immunocompromised patient. Lipopolysaccharide (LPS), the major surface antigen of P. aeruginosa, is immunogenic and elieits protective antibodies in animals. The O-polysaccharids (O-PS) from international Antigenic typing Scheme (IATS) 10, the antigenic determinant of LPS, was coupled to recombinant exoprotein A (rPA) through adipic acid dihydrazide (ADH) mediated by carbodiimide condensation reaction. Mice were immunized with the conjugate emulsifield with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-T) and freund's adjuvants. The conjiugate emulsified with MPL-T adjuvant elicited the highest level of IgG and IgM followed by freuns's adjuvant. IgG titers using both MPL-T and freund's adjuvants were recorded to be higher than IgM titers after the second post of the immunization. Immunization of mice with the prepared conjugates emulsified with MPL-T and freund's adjvaided provide high level of protection (100%) against ten times the LD50 of homologous strain of P. aeruginsoa. the elicited high IgG level and the in vivo protection test results provided good evidences for the possible protection of the conjugate aginst subsequent infection with the pathogen. These findings will enable us to use it as protective vaccine candidate (authors).

  10. Synthesis, characterization and in vitro evaluation of methotrexate conjugated fluorescent carbon nanoparticles as drug delivery system for human lung cancer targeting.

    Science.gov (United States)

    Ajmal, Muhammad; Yunus, Uzma; Matin, Abdul; Haq, Noaman Ul

    2015-12-01

    Nanotechnology based cancer therapeutics have rapidly advanced towards the solution of many limitations associated with other drug delivery agents such as nonspecific distribution within the body, low water solubility and non-biocompatibility. Carbon nanoparticles have demonstrated unique properties that are useful to combat with these issues, including their properties dependent on size, high stability in different solvents, compatible size for drug delivery and ease of surface modifications. Fluorescent carbon nanoparticles with good water solubility were obtained from a carbohydrate source by acid assisted ultrasonic treatment at 35kHz for 4h. This simple and economical method can be used for large scale production. Electron microscopic, spectroscopic and thermo gravimetric analysis techniques were used to characterize these carbon nanoparticles. Functionalized CNPs were further conjugated with anticancer drug-methotrexate and used as fluorescent nano-carriers. In this research work, we determined the in vitro bioactivity of CNPs-methotrexate conjugates by lactate dehydrogenase assay, cell adhesion assay and sulforhodamine B assay in human lung carcinoma cell line (H157). The CNPs showed promising biocompatibility and CNPs-MTX conjugates demonstrated potent cytotoxic effects and high anticancer activities in human lung cancer cell line. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Methyl 6-Amino-6-deoxy-d-pyranoside-Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism.

    Science.gov (United States)

    Li, Taoli; Gao, Xiangqian; Yang, Liu; Shi, Yunli; Gao, Qingzhi

    2016-05-19

    Methyl 6-aminodeoxy-d-pyranoside-derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)-mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT-mediated transport of the complexes was investigated with a cell-based fluorescence competition assay and GLUT-inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside-conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT-mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg-effect-targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside-conjugated platinum(II) complexes as lead compounds for further preclinical evaluation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Conjugated Polymers for Energy Production

    DEFF Research Database (Denmark)

    Livi, Francesco

    for scalable PSCs fully printed under ambient conditions [Adv. Energy Mater. 2015, 5, 1402186]. PPDTBT resulted to be the conjugated polymer with the best photovoltaic performance within the 104 synthesized macromolecules. Therefore, further studies have been done on such material. The impact of side chain......This dissertation is aimed at developing materials for flexible, large area, ITO-free polymer solar cells (PSCs) fully printed under ambient conditions. A large screening of conjugated polymers, both novel and well-known materials, has been carried out in order to find suitable candidates.......The reactivity of DArP has been further studied and applied to the synthesis of fluorinated copolymers featuring thiophene, which are largely used materials for organic electronics. In particular, by moving the bromine functionality from one monomer to the other, a big impact on the reactivity has been observed...

  13. Organometallic B12-DNA conjugate

    DEFF Research Database (Denmark)

    Hunger, Miriam; Mutti, Elena; Rieder, Alexander

    2014-01-01

    Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets...... with transcobalamin (TC), but not so efficient with the homologous glycoproteins intrinsic factor and haptocorrin. Binding of the B12 octadecanucleotide to TC suggests the capacity of the B12 moiety to serve as a natural vector for specific transport of single stranded, organometallic oligonucleotide loads from...... in humans and animals, through the endogenous B12 transport systems. Binding of the organometallic B12 octadecanucleotide to the three important human proteins of B12 transport was studied, to examine its structural suitability for the task of eventual in vivo oligonucleotide delivery. Binding was efficient...

  14. Synthesis and evaluation of radiolabeled, folic acid-PEG conjugated, amino silane coated magnetic nanoparticles in tumor bearing Balb/C mice

    Directory of Open Access Journals (Sweden)

    Razjouyan Javad

    2015-07-01

    Full Text Available To design a potent agent for positron emission tomography/magnetic resonance imaging (PET/MRI imaging and targeted magnetic hyperthermia-radioisotope cancer therapy radiolabeled surface modified superparamagnetic iron oxide nanoparticles (SPIONs were used as nanocarriers. Folic acid was conjugated for increasing selective cellular binding and internalization through receptor-mediated endocytosis. SPIONs were synthesized by the thermal decomposition of tris (acetylacetonato iron (III to achieve narrow and uniform nanoparticles. To increase the biocompatibility of SPIONs, they were coated with (3-aminopropyl triethoxysilane (APTES, and then conjugated with synthesized folic acid-polyethylene glycol (FA-PEG through amine group of (3-aminopropyl triethoxysilane. Finally, the particles were labeled with 64Cu (t1/2 = 12.7 h using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono (N-hydroxy succinimide ester DOTA-NHS chelator. After the characterization of SPIONs, their cellular internalization was evaluated in folate receptor (FR overexpressing KB (established from a HeLa cell contamination and mouse fibroblast cell (MFB lines. Eventually, active and passive targeting effects of complex were assessed in KB tumor-bearing Balb/C mice through biodistribution studies. Synthesized bare SPIONs had low toxicity effect on healthy cells, but surface modification increased their biocompatibility. Moreover, KB cells viability was reduced when using folate conjugated SPIONs due to FR-mediated endocytosis, while having little effect on healthy cells (MFB. Moreover, this radiotracer had tolerable in vivo characteristics and tumor uptake. In the receptor blocked case, tumor uptake was decreased, indicating FR-specific uptake in tumor tissue while enhanced permeability and retention effect was major mechanism for tumor uptake.

  15. Design, synthesis and biological evaluation of novel L-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors.

    Science.gov (United States)

    Wang, Han; Xu, Renyang; Shi, Yongying; Si, Longlong; Jiao, Pingxuan; Fan, Zibo; Han, Xu; Wu, Xingyu; Zhou, Xiaoshu; Yu, Fei; Zhang, Yongmin; Zhang, Liangren; Zhang, Lihe; Zhou, Demin; Xiao, Sulong

    2016-03-03

    Since the influenza viruses can rapidly evolve, it is urgently required to develop novel anti-influenza agents possessing a novel mechanism of action. In our previous study, two pentacyclic triterpene derivatives (Q8 and Y3) have been found to have anti-influenza virus entry activities. Keeping the potential synergy of biological activity of pentacyclic triterpenes and l-ascorbic acid in mind, we synthesized a series of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives (18-26, 29-31, 35-40 and 42-43). Moreover, we evaluated these novel compounds for their anti-influenza activities against A/WSN/33 virus in MDCK cells. Among all evaluated compounds, the 2,3-O,O-dibenzyl-6-deoxy-l-ascorbic acid-betulinic acid conjugate (30) showed the most significant anti-influenza activity with an EC50 of 8.7 μM, and no cytotoxic effects on MDCK cells were observed. Time-of-addition assay indicated that compound 30 acted at an early stage of the influenza life cycle. Further analyses revealed that influenza virus-induced hemagglutination of chicken red blood cells was inhibited by treatment of compound 30, and the interaction between the influenza hemagglutinin (HA) and compound 30 was determined by surface plasmon resonance (SPR) with a dissociation constant of KD = 3.76 μM. Finally, silico docking studies indicated that compound 30 and its derivative 31 were able to occupy the binding pocket of HA for sialic acid receptor. Collectively, these results suggested that l-ascorbic acid-conjugated pentacyclic triterpenes were promising anti-influenza entry inhibitors, and HA protein associated with viral entry was a promising drug target. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Segmented conjugated polymers

    Indian Academy of Sciences (India)

    Segmented conjugated polymers, wherein the conjugation is randomly truncated by varying lengths of non-conjugated segments, form an interesting class of polymers as they not only represent systems of varying stiffness, but also ones where the backbone can be construed as being made up of chromophores of varying ...

  17. Synthesis of enantiomerically pure (purin-6-yl)phenylalanines and their nucleosides, a novel type of purine-amino acid conjugates.

    Science.gov (United States)

    Capek, Petr; Pohl, Radek; Hocek, Michal

    2005-09-30

    [Chemical reaction: See text] Enantiomerically or diastereomerically pure 4-(purin-6-yl)phenylalanines, a novel type of stable amino acid-purine conjugates, were synthesized by palladium-catalyzed cross-coupling reactions of protected 4-boronophenylalanines or 4-(trimethylstanyl)phenylalanines with diverse 6-halopurines (9-benzyl-6-halopurines and 9-(tetrahydropyran-2-yl)-6-halopurines as well as acyl- and silyl-protected 6-halopurine ribonucleosides and 2-deoxyribonucleosides). Free purine bases and nucleosides bearing (S)- or (R)-phenylalanine in position 6 were obtained after complete deprotection of the products of cross-coupling reactions. Reactivity trends for both of these cross-coupling and deprotection protocols have been compared in terms of practicability, efficiency, and stereoselectivity.

  18. Facile Synthesis of Well-Defined MDMO-PPV Containing (TriBlock—Copolymers via Controlled Radical Polymerization and CuAAC Conjugation

    Directory of Open Access Journals (Sweden)

    Neomy Zaquen

    2015-02-01

    Full Text Available A systematic investigation into the chain transfer polymerization of the so-called radical precursor polymerization of poly(p-phenylene vinylene (PPV materials is presented. Polymerizations are characterized by systematic variation of chain transfer agent (CTA concentration and reaction temperature. For the chain transfer constant, a negative activation energy of −12.8 kJ·mol−1 was deduced. Good control over molecular weight is achieved for both the sulfinyl and the dithiocarbamate route (DTC. PPVs with molecular weights ranging from thousands to ten thousands g·mol−1 were obtained. To allow for a meaningful analysis of the CTA influence, Mark–Houwink–Kuhn–Sakurada (MHKS parameters were determined for conjugated MDMO-PPV ([2-methoxy-5-(3',7'-dimethyloctyloxy]-1,4-phenylenevinylene to α = 0.809 and k = 0.00002 mL·g−1. Further, high-endgroup fidelity of the CBr4-derived PPVs was proven via chain extension experiments. MDMO-PPV-Br was successfully used as macroinitiator in atom transfer radical polymerization (ATRP with acrylates and styrene. A more polar PPV counterpart was chain extended by an acrylate in single-electron transfer living radical polymerization (SET-LRP. In a last step, copper-catalyzed azide alkyne cycloaddition (CuAAC was used to synthesize block copolymer structures. Direct azidation followed by macromolecular conjugation showed only partial success, while the successive chain extension via ATRP followed by CuAAC afforded triblock copolymers of the poly(p-phenylene vinylene-block-poly(tert-butyl acrylate-block-poly(ethylene glycol (PPV-b-PtBuA-b-PEG.

  19. Synthesis of polyglutamide-based metal-chelating polymers and their site-specific conjugation to trastuzumab for auger electron radioimmunotherapy.

    Science.gov (United States)

    Lu, Yijie; Ngo Ndjock Mbong, Ghislaine; Liu, Peng; Chan, Conrad; Cai, Zhongli; Weinrich, Dirk; Boyle, Amanda J; Reilly, Raymond M; Winnik, Mitchell A

    2014-06-09

    Three types of metal-chelating polymers (MCPs) with hydrazide end groups were synthesized. (1) The first set of polymers (the F-series) was synthesized with a furan end group, and all of the pendant groups along the chain carried only a diethylenetriaminepentaacetic acid (DTPA) metal-chelating functionality. The hydrazide was introduced via a Diels-Alder reaction between the furan and 3,3'-N-[ε-maleimidocaproic acid] hydrazide (EMCH). (2) The P-series polymers was designed to carry several copies of a nuclear-localization peptide sequence (NLS peptides, CGYGPKKKRKVGG, harboring the NLS from the simian virus 40 large T-antigen) in addition to the DTPA metal-chelating groups. (3) The third type of polymer (the P-Py series) was a variation of the P-series polymers but with the introduction of a small number of pyrene chromophores along the backbone to allow for UV measurement of the incorporation of the MCPs into trastuzumab (tmab). These hydrazide-terminated polymers were site-specifically conjugated to aldehyde groups generated by NaIO4 oxidation of the pendant glycan in the Fc domain of tmab. The immunoconjugates were radiolabeled with (111)In and analyzed by SE-HPLC to confirm the attachment of the polymer to the antibody. HER2 binding assays demonstrated that neither the MCPs nor the presence of the NLS peptides interfered with specific antigen recognition on SK-Br-3 cells, although nonspecific binding was increased by polymer conjugation. Our results suggest that MCPs can be site-specifically attached to antibodies via oxidized glycans in the Fc domain and labeled with (111)In to construct radioimmunoconjugates with preserved immunoreactivity.

  20. Design, synthesis, and application of a hydrazide-functionalized isotope-coded affinity tag for the quantification of oxylipid-protein conjugates.

    Science.gov (United States)

    Han, Bingnan; Stevens, Jan F; Maier, Claudia S

    2007-05-01

    An isotopically coded affinity probe was developed and evaluated for the characterization and quantification of proteins adducted by 2-alkenals derived from lipid peroxidation (LPO) processes. Lipid-derived 2-alkenals, such as acrolein and 4-hydroxy-2-nonenal (HNE), have the ability to react with cysteine, histidine, and lysine residues in proteins, thus causing protein damage and loss of protein function. Such modifications of proteins are difficult to characterize in biological samples by mass spectrometry due to the complexity of protein extracts and the low abundance of adducted proteins. The novel aldehyde-reactive, hydrazide-functionalized, isotope-coded affinity tag (HICAT) described in this study was found effective for the selective isolation, detection, and quantification of Michael-type adducts of 2-alkenals with proteins using a combination of affinity isolation, nanoLC, and matrix-assisted laser desorption ionization tandem mass spectrometry (MALDI-MS/MS). The chemical and mass spectrometric properties of the new probe are demonstrated on a model protein treated with HNE. The efficacy of HICAT for the analysis of complex samples was tested using preparations of mitochondrial proteins that were modified in vitro with HNE. The potential of the HICAT strategy for the identification, characterization, and quantification of in vivo oxylipid-protein conjugates is demonstrated on cardiac mitochondrial protein preparations, in which, for example, the ADP/ATP translocase 1 was found adducted to the 2-alkenals, acrolein and 4-hydroxy-2-hexenal, at Cys-256.

  1. Synthesis, characterization and optical studies of conjugated Schiff base polymer containing thieno[3,2-b]thiophene and 1,2,4-triazole groups

    Science.gov (United States)

    Cetin, Adnan; Korkmaz, Adem; Kaya, Esin

    2018-02-01

    A conjugated polyschiff base (poly(N-thieno[3,2-b]thiophen-2-yl)methylene)-1H-1,2,4-triazol-5-amine) poly(TTMA)) was synthesized by condensation polymerization between thieno[3,2-b]thiophene-2,5-dicarboxaldehyde and 3,5-diamino-1,2,4-triazole. The poly(TTMA) was characterized by FT-IR, 1H NMR, 13C NMR spectra and thermal analysis. The number average molecular weight (Mn) and polydispersity index of the poly(TTMA) were determined by gel permeation chromatography (GPC). In addition, the optical properties of the poly(TTMA) solutions were investigated at different molarities. The band gap Eg value of the poly(TTMA) decreased with the increasing molarity. The absorption band edge values of the poly(TTMA) decreased as the molarity increased. The average transmittance values of the poly(TTMA) increased with the increasing molarity and the highest values of molar extinction coefficient also were found in the near ultraviolet region. Its values decreased with the increasing molarity. These results showed that the poly(TTMA) can be used for the fabrication of many optoelectronic devices due to its suitable optical properties and low optical band gap.

  2. Enantioselective conjugate addition nitro-Mannich reactions: solvent controlled synthesis of acyclic anti- and syn-β-nitroamines with three contiguous stereocenters.

    Science.gov (United States)

    Anderson, James C; Stepney, Gregory J; Mills, Matthew R; Horsfall, Lisa R; Blake, Alexander J; Lewis, William

    2011-04-01

    We report an enantioselective conjugate addition nitro-Mannich reaction protocol which combines dialkylzinc, aromatic nitro alkene and imine to form two C-C bonds and three contiguous stereocenters in one reaction vessel. Absolute stereochemistry was controlled from the initial 1,4-addition of dialkylzinc to aromatic nitroalkenes by known copper-chiral ligand catalysts. The choice of solvent dictated the formation of either the syn,anti or syn,syn diastereoisomers, two of the four possible diastereoisomers. The syn,syn isomer is a rare example of a syn-selective nitro-Mannich reaction. The diastereoselectivity is dependent upon the presence or not of Zn(O(2)CCF(3))(2) in the reaction mixture and empirical transition state models are proposed to account for the observed stereochemical course of the two reaction conditions. The extent of enantioselectivity and structural diversity of the process is limited by current methodology for the catalytic asymmetric addition of dialkylzincs to nitrostyrenes. The synthetically versatile products are the most complex β-nitro amines prepared using the nitro-Mannich reaction and are formed in high yield and enantioselectivity.

  3. Cyclometalated Iridium(III) Complexes Containing 4,4'-π-Conjugated 2,2'-Bipyridine Derivatives as the Ancillary Ligands: Synthesis, Photophysics, and Computational Studies.

    Science.gov (United States)

    Sarma, Monima; Chatterjee, Tanmay; Bodapati, Ramakrishna; Krishnakanth, Katturi Naga; Hamad, Syed; Rao, S Venugopal; Das, Samar K

    2016-04-04

    This article demonstrates a series of cyclometalated Ir(III) complexes of the type [Ir(III)(C^N)2(N^N)](PF6), where C^N is 2-phenylpyridine, and N^N corresponds to the 4,4'-π-conjugated 2,2'-bipyridine ancillary ligands. All these compounds were synthesized through splitting of the binuclear dichloro-bridged complex precursor, [Ir(C^N)2(μ-Cl)]2, with the appropriate bipyridine ligands followed by the anion exchange reaction. The linear and nonlinear absorption properties of the synthesized complexes were investigated. The absorption spectra of all the title complexes exhibit a broad structureless feature in the spectral region of 350-700 nm with two bands being well-resolved in most of the cases. The structures of all the compounds were modeled in dichloromethane using the density functional theory (DFT) algorithm. The nature of electronic transitions was further comprehended on the basis of time-dependent DFT analysis, which indicates that the origins of various bands are primarily due to intraligand charge transfer transitions along with mixed-metal and ligand-centered transitions. The synthesized compounds are found to be nonemissive at room temperature because of probable nonradiative deactivation pathways of the T1 state that compete with the radiative (phosphorescence) decay modes. However, the frozen solutions of compounds Ir(MS 3) and Ir(MS 5) phosphoresce at the near-IR region, the other complexes remaining nonemissive up to 800 nm wavelength window. The two-photon absorption studies on the synthesized complexes reveal that values of the absorption cross-section are quite notable and lie in the range of 300-1000 GM in the picosecond case and 45-186 GM in the femtosecond case.

  4. Methotrexate and epirubicin conjugates as potential antitumor drugs

    Directory of Open Access Journals (Sweden)

    Szymon Wojciech Kmiecik

    2017-07-01

    Full Text Available Introduction: The use of hybrid molecules has become one of the most significant approaches in new cytotoxic drug design. This study describes synthesis and characterization of conjugates consisting of two well-known and characterized chemotherapeutic agents: methotrexate (MTX and epirubicin (EPR. The synthesized conjugates combine two significant anticancer strategies: combinatory therapy and targeted therapy. These two drugs were chosen because they have different mechanisms of action, which can increase the anticancer effect of the obtained conjugates. MTX, which is a folic acid analog, has high cytotoxic properties and can serve as a targeting moiety that can reach folate receptors (FRs overexpresing tumor cells. Combination of nonselective drugs such as EPR with MTX can increase the selectivity of the obtained conjugates, while maintaining the high cytotoxic properties.Materials and methods: Conjugates were purified by RP-HPLC and the structure was investigated by MS and MS/MS methods. The effect of the conjugates on proliferation of LoVo, LoVo/Dx, MCF-7 and MV-4-11 human cancer cell lines was determined by SRB or MTT assay.Results: The conjugation reaction results in the formation of monosubstituted (α, γ and disubstituted MTX derivatives. In vitro proliferation data demonstrate that the conjugates synthesized in our study show lower cytotoxic properties than both chemotherapeutics used alone.Discussion: Epirubicin cytotoxicity was not observed in obtained conjugates. Effective drugs release after internalization needs further investigation.

  5. Efficient synthesis of [18F]FPyME: A new approach for the preparation of maleimide-containing prosthetic groups for the conjugation with thiols.

    Science.gov (United States)

    Cavani, Melanie; Bier, Dirk; Holschbach, Marcus; Coenen, Heinz H

    2017-01-01

    An improved high yielding radiosynthesis of the known thiol-reactive maleimide-containing prosthetic group1-[3-(2-[ 18 F]fluoropyridine-3-yloxy)propyl]pyrrole-2,5-dione ([ 18 F]FPyME) is described. The target compound was obtained by a two-step one-pot procedure starting from a maleimide-containing nitro-precursor that was protected as a Diels-Alder adduct with 2,5-dimethylfurane. Nucleophilic radiofluorination followed by heat induced deprotection through a Retro Diels Alder reaction yielded, after chromatographic isolation, [ 18 F]FPyME with a radiochemical yield of 20% in about 60 min overall synthesis time. A variety of other [ 18 F]fluoropyridine based maleimide-containing prosthetic groups should be accessible via the described synthetic strategy. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Methods to Design and Synthesize Antibody-Drug Conjugates (ADCs

    Directory of Open Access Journals (Sweden)

    Houzong Yao

    2016-02-01

    Full Text Available Antibody-drug conjugates (ADCs have become a promising targeted therapy strategy that combines the specificity, favorable pharmacokinetics and biodistributions of antibodies with the destructive potential of highly potent drugs. One of the biggest challenges in the development of ADCs is the application of suitable linkers for conjugating drugs to antibodies. Recently, the design and synthesis of linkers are making great progress. In this review, we present the methods that are currently used to synthesize antibody-drug conjugates by using thiols, amines, alcohols, aldehydes and azides.

  7. Single-step green synthesis and characterization of gold-conjugated polyphenol nanoparticles with antioxidant and biological activities

    Directory of Open Access Journals (Sweden)

    Sanna V

    2014-10-01

    , RSV, and FS, respectively. Nanoprototypes exhibited remarkable in vitro stability in various media, suggesting that NP surface coating with phytochemicals prevents aggregation in different simulated physiological conditions. The scavenging activities for DPPH and ABTS were highly correlated with EGCG, RSV, and FS content. Moreover, high correlation coefficients between the ABTS and DPPH values were found for the prepared nanosystems. EGCG-GNPs induce a dose-dependent reduction on SH-SY5Y-CFP-DEVD-YFP cell viability that is likely to involve the activation of the apoptotic pathways, similarly to free EGCG, as suggested by the processing of the CFP-DEVD-YFP reporter. Conclusion: These results prompted us to propose the ecofriendly synthesized EGCG-, RSV-, and FS-based nanogold conjugates as suitable carriers for bioactive polyphenols to be used for the treatment of disorders associated with oxidative stress, including neurodegenerative disorders, cardiovascular disease, and cancer. Keywords: gold nanoparticles, epigallocatechin-3-gallate, resveratrol, fisetin, antioxidant activity, SH-SY5Y-CFP-DEVD-YFP cells

  8. Qualidade conjugal: mapeando conceitos

    Directory of Open Access Journals (Sweden)

    Clarisse Mosmann

    2006-12-01

    Full Text Available Apesar da ampla utilização do conceito de qualidade conjugal, identifica-se falta de clareza conceitual acerca das variáveis que o compõem. Esse artigo apresenta revisão da literatura na área com o objetivo de mapear o conceito de qualidade conjugal. Foram analisadas sete principais teorias sobre o tema: Troca Social, Comportamental, Apego, Teoria da Crise, Interacionismo Simbólico. Pelos postulados propostos nas diferentes teorias, podem-se identificar três grupos de variáveis fundamentais na definição da qualidade conjugal: recursos pessoais dos cônjuges, contexto de inserção do casal e processos adaptativos. Neste sentido, a qualidade conjugal é resultado do processo dinâmico e interativo do casal, razão deste caráter multidimensional.

  9. Conjugated Polymer Solar Cells

    National Research Council Canada - National Science Library

    Paraschuk, Dmitry Y

    2006-01-01

    This report results from a contract tasking Moscow State University as follows: Conjugated polymers are promising materials for many photonics applications, in particular, for photovoltaic and solar cell devices...

  10. Polymers for Protein Conjugation

    Directory of Open Access Journals (Sweden)

    Gianfranco Pasut

    2014-01-01

    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

  11. Synthesis, physiochemical characterization, and in vitro antitumor activity of the amide and pH cleavable hydrazone conjugates of γ-tocotrienol isomer of vitamin E with methoxy-poly(ethylene) glycol.

    Science.gov (United States)

    Abu-Fayyad, Ahmed; Nazzal, Sami

    2017-08-30

    The anticancer activity of water soluble methoxy polyethylene glycol (mPEG) derivatives of tocotrienol (T3) isomers of vitamin E was previously found to be reduced when compared to the parent free isomers. This could be due to the ester bond formation between the mPEG and the 6-OH group on the chroman moiety of the T3 isomer. To further investigate, the objectives of the current study were to (1) synthesize and characterize stable amide and cleavable hydrazone conjugates between mPEG and carbon-5 on the chroman moiety of T3, and (2) examine the cytotoxicity of the newly synthesized mPEG conjugates against breast (MCF-7 and MDA-MB-231) and pancreatic (BxPC-3 and PANC-1) cancer cells. Conjugates were synthesized by direct conjugation of succinyl chloride derivatives of mPEG to the α-tocopherol and γ-tocotrienol isomers of vitamin E, and were characterized by 1 H NMR, FT-IR, and mass spectrometry. The micelles of the amide and hydrazone self-assembled conjugates were characterized for size, zeta, CMC, and stability at different pH media. The hydrolysis of the hydrazone conjugate was pH dependent with highest release at acidic (pH 5.5) conditions, whereas the amide conjugate was stable in all tested media. The amide conjugate nonetheless showed greater cytotoxicity than the hydrazone conjugate, which suggested that maintaining solubility and the presence of free 6-OH group are important for γ-T3 to exert anticancer activity in vitro. The results from the current study demonstrated the importance of considering the nature of the chemical bond between T3 and mPEG when designing functional ingredients for use in drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. D-A conjugated polymers containing substituted thiophene, 1,3,4 ...

    Indian Academy of Sciences (India)

    s12039-016-1145-6. D-A conjugated polymers containing substituted thiophene,. 1,3,4-oxadiazole and non-conjugation linkers: Synthesis and study of optical and electrochemical properties. PRASHANTH KUMAR K Ra, UDAYAKUMAR Da,∗ ...

  13. Asymmetric Conjugate Addition of Grignard Reagents to Pyranones

    NARCIS (Netherlands)

    Mao, Bin; Fananas Mastral, Martin; Feringa, Ben L.

    2013-01-01

    An efficient enantioselective synthesis of lactones was developed based on the catalytic asymmetric conjugate addition (ACA) of alkyl Grignard reagents to pyranones. The use of 2H-pyran-2-one for the first time in the ACA with Grignard reagents allows for a variety of further transformations to

  14. Flurbiprofen- and Suprofen-Dextran Conjugates: Synthesis ...

    African Journals Online (AJOL)

    Erah

    (SD-110) was 64.23 and 41.50% which compare well with those of their parent drugs - flurbiprofen. (72.60%) and ... analysis were purchased from Merck India. All ..... observed for SD-110 was 6.06. All the results of biological evaluation were statistically significant (p < 0.05) in relation to the control sample. DISCUSSION.

  15. DNA-cell conjugates

    Science.gov (United States)

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2016-05-03

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  16. Photoluminescence in conjugated polymers

    International Nuclear Information System (INIS)

    Furst, J.E.; Laugesen, R.; Dastoor, P.; McNeill, C.

    2002-01-01

    Full text: Conjugated polymers combine the electronic and optical properties of semiconductors with the processability of polymers. They contain a sequence of alternate single and double carbon bonds so that the overlap of unhybridised p z orbitals creates a delocalised ρ system which gives semiconducting properties with p-bonding (valence) and p* -antibonding (conduction) bands. Photoluminesence (PL) in conjugated polymers results from the radiative decay of singlet excitons confined to a single chain. The present work is the first in a series of studies in our laboratory that will characterize the optical properties of conjugated polymers. The experiment involves the illumination of thin films of conjugated polymer with UV light (I=360 nm) and observing the subsequent fluorescence using a custom-built, fluorescence spectrometer. Photoluminesence spectra provide basic information about the structure of the polymer film. A typical spectrum is shown in the accompanying figure. The position of the first peak is related to the polymer chain length and resolved multiple vibronic peaks are an indication of film structure and morphology. We will also present results related to the optical degradation of these materials when exposed to air and UV light

  17. Ultraviolet phase conjugation

    International Nuclear Information System (INIS)

    Slatkine, M.; Bigio, I.J.; Fisher, R.A.; Maloney, M.L.; Busse, J.R.; Tercovich, R.G.; Feldman, B.J.

    1981-01-01

    Diffraction-limited phase conjugate reflection of an injection-locked high-power (approx. 1 MW) ultraviolet excimer laser beam has been demonstrated via stimulated Brillouin scattering. Reflectivities higher than 70% were attained. Limitations as well as coherence and power requirements for image retention are discussed

  18. Crisis and Conjugal Power

    Science.gov (United States)

    Bahr, Stephen L.; Rollins, Boyd C.

    1971-01-01

    It was hypothesized that the more equalitarian the conjugal power structure in a noncrisis situation, the more likely the relative marital power will change during a crisis. This was tested using an observational experimental method, and the hypothesis was supported. (Author/CG)

  19. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  20. Synthesis of Tumor-avid Photosensitizer-Gd(III)DTPA conjugates: impact of the number of gadolinium units in T1/T2 relaxivity, intracellular localization, and photosensitizing efficacy.

    Science.gov (United States)

    Goswami, Lalit N; White, William H; Spernyak, Joseph A; Ethirajan, Manivannan; Chen, Yihui; Missert, Joseph R; Morgan, Janet; Mazurchuk, Richard; Pandey, Ravindra K

    2010-05-19

    To develop novel bifunctional agents for tumor imaging (MR) and photodynamic therapy (PDT), certain tumor-avid photosensitizers derived from chlorophyll-a were conjugated with variable number of Gd(III)aminobenzyl DTPA moieties. All the conjugates containing three or six gadolinium units showed significant T(1) and T(2) relaxivities. However, as a bifunctional agent, the 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) containing 3Gd(III) aminophenyl DTPA was most promising with possible applications in tumor-imaging and PDT. Compared to HPPH, the corresponding 3- and 6Gd(III)aminobenzyl DTPA conjugates exhibited similar electronic absorption characteristics with a slightly decreased intensity of the absorption band at 660 nm. However, compared to HPPH, the excitation of the broad "Soret" band (near 400 nm) of the corresponding 3Gd(III)aminobenzyl-DTPA analogues showed a significant decrease in the fluorescence intensity at 667 nm.

  1. Development of antibacterial conjugates using sulfamethoxazole with monocyclic terpenes: A systematic medicinal chemistry based computational approach.

    Science.gov (United States)

    Swain, Shasank S; Paidesetty, Sudhir K; Padhy, Rabindra N

    2017-03-01

    . aureus) and -10.19 (conjugate-2 against S. pneumoniae. Conjugates-2 and -5 were the most effective antibacterials based on Lipinski rule of five with lethal doses 3471 and 3500mg/kg, respectively and toxicity class levels. Conjugate-2 and conjugate-5 were more effective than individual monoterpenes and SMZ, against pathogenic bacteria. Synthesis, characterization and in vitro antibacterial study with acute toxicity testing for Wister rat model of the conjugate-5 could land at success in the recorded computational trial and it could be promoted for synthesis in the control of MDR bacteria. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. High Mobility Conjugated Polymers

    Science.gov (United States)

    2007-10-20

    blends with poly(3- hexylthiophene) (PHT) could be readily fabricated as uniform nanofibers by co- electrospinning their solutions with another solution...We have demonstrated that nanofibers of conjugated 10 - polymers and their blends could be conveniently fabricated by electrospinning . Furthermore, we...luminance o - - characteristics of an ITO/ PEDOT /TAPC k D r a Vol gt, V, (V) /BPQ-PPO/LiF/A! device are shown in Fig. 30. (A) Current density-voltage

  3. New hyper-crosslinked partly conjugated networks with tunable composition by spontaneous polymerization of ethynylpyridines with bis(bromomethyl)arenes: Synthesis, spectral properties, and activity in CO2 capture

    Czech Academy of Sciences Publication Activity Database

    Petrášová, S.; Zukal, Arnošt; Brus, Jiří; Balcar, Hynek; Pastva, Jakub; Zednik, J.; Sedláček, J.

    2013-01-01

    Roč. 214, č. 24 (2013), s. 2856-2866 ISSN 1022-1352 R&D Projects: GA ČR(CZ) GAP108/11/1661 Institutional support: RVO:61388955 ; RVO:61389013 Keywords : CO2 capture * Conjugated polymers * ethynylpyridine Subject RIV: CF - Physical ; Theoretical Chemistry ; CD - Macromolecular Chemistry (UMCH-V) Impact factor: 2.451, year: 2013

  4. Poly(trimethylsilylcyclooctatetraene): A soluble conjugated polyacetylene via olefin metathesis

    Energy Technology Data Exchange (ETDEWEB)

    Ginsburg, E.J.; Gorman, C.B.; Grubbs, R.H.; Marder, S.R. (California Institute of Technology, Pasadena (USA))

    1989-09-13

    highly conjugated polymers, such as polyacetylene, polythiophene, and poly(p-phenylene vinylene), have been the subject of intensive research due to their intriguing optical and electronic properties. These parent systems are highly desirable for experimental and theoretical studies due to their simplicity. Their intractability, however, has made characterization an arduous task, and insolubility has severely limited their applications. Researchers have successfully circumvented these obstacles by synthesizing soluble alkyl- and alkoxy-substituted polythiphenes and poly(p-phenylene vinylenes). Analogous soluble highly conjugated polyacetylene derivatives have proven more elusive. The authors report here the synthesis of such a polymer using ring-opening metathesis polymerization (ROMP).

  5. PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

    DEFF Research Database (Denmark)

    2004-01-01

    . Subsequently, the immunomodulating substance is also bound in a chemoselective manner, to give a dendrimer conjugate with a well-defined structure and connectivity and containing a precise, pre-determined ratio of carbohydrate to immunomodulating substance. The invention also relates to novel dendrimer......A method for the synthesis of dendrimer conjugates having a well-defined chemical structure, comprising one or more carbohydrate moieties and one or more immunomodulating substances coupled to a dendrimer, is presented. First, the carbohydrate is bound to the dendrimer in a chemoselective manner...

  6. Recent Advances in Polymer Organic Light-Emitting Diodes (PLED) Using Non-conjugated Polymers as the Emitting Layer and Contrasting Them with Conjugated Counterparts

    Science.gov (United States)

    Wong, Michael Y.

    2017-11-01

    Polymer organic light-emitting diodes (PLED) are one of the most studied subjects in flexible electronics thanks to their economical wet fabrication procedure for enhanced price advantage of the product device. In order to optimize PLED efficiency, correlating the polymer structure with the device performance is essential. An important question for the researchers in this field is whether the polymer backbone is conjugated or not as it affects the device performance. In this review, recent advances in non-conjugated polymers employed as the emitting layer in PLED devices are first discussed, followed by their contrast with the conjugated counterparts in terms of polymer synthesis, sample quality, physical properties and device performances. Such comparison between conjugated and non-conjugated polymers for PLED applications is rarely attempted, and; hence, this review shall provide a useful insight of emitting polymers employed in PLEDs.

  7. Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine.

    Science.gov (United States)

    Aqeel, Yousuf; Siddiqui, Ruqaiyyah; Anwar, Ayaz; Shah, Muhammad Raza; Khan, Naveed Ahmed

    2015-12-14

    Acanthamoeba keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold-conjugated chlorhexidine nanoparticles. The synthesis was confirmed using UV-visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a gold-conjugated chlorhexidine complex at m/z 699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 μM. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth

  8. Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine

    Science.gov (United States)

    Aqeel, Yousuf; Siddiqui, Ruqaiyyah; Anwar, Ayaz; Shah, Muhammad Raza

    2015-01-01

    Acanthamoeba keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold-conjugated chlorhexidine nanoparticles. The synthesis was confirmed using UV-visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a gold-conjugated chlorhexidine complex at m/z 699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 μM. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth

  9. Green ultrasound-assisted three-component click synthesis of novel 1H-1,2,3-triazole carrying benzothiazoles and fluorinated-1,2,4-triazole conjugates and their antimicrobial evaluation

    Directory of Open Access Journals (Sweden)

    Rezki Nadjet

    2017-09-01

    Full Text Available The present study describes an efficient and ecofriendly, ultrasound, one-pot click cycloaddition approach for the construction of a novel series of 1,4-disubstituted-1,2,3-triazoles tethered with fluorinated 1,2,4-triazole-benzothiazole molecular conjugates. It involved three-component condensation of the appropriate bromoacetamide benzothiazole, sodium azide and 4-alkyl/aryl-5-(2-fluorophenyl-3-(prop-2-ynylthio-1,2,4-triazoles 4a-e through a Cu(I-catalyzed 1,3-dipolar cycloaddition reaction. This approach involves in situ generation of azidoacetamide benzothiazole, followed by condensation with terminal alkynes in the presence of CuSO4/Na-ascorbate in aqueous DMSO under both conventional and ultrasound conditions. Some of the designed 1,2,3-triazole conjugates 6a-o were recognized for their antimicrobial activity against some bacterial and fungal pathogenic strains.

  10. A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E-γ-aminated nitroalkenes derived from L-α-amino acids

    Directory of Open Access Journals (Sweden)

    Vera Lúcia Patrocinio Pereira

    2013-04-01

    Full Text Available New chiral (S,E-γ-N,N-dibenzylated nitroalkenes 2a–c were synthesized from natural L-(α-amino acids in five steps with overall yields of 68–88%. The conjugate addition of hydride, methoxide, nitronate and azide nucleophiles to 2a–c led to the corresponding chiral 1,3-nitroamines in 74–90% yield. The conjugate addition of cyanide anion to 2a,b was followed by HNO2 elimination affording chiral aminated acrylonitriles (73–98%. On the other hand, the azide anion reacted with 2a, in acetonitrile, via a [3 + 2]-cycloaddition in which HNO2 was lost, providing the corresponding 1,2,3-triazole derivative. Direct reduction of 1,3-nitroamine derivatives 9a,b produced the corresponding 1,3-diamines in good yields.

  11. Synthesis, singlet-oxygen photogeneration, two-photon absorption, photo-induced DNA cleavage and cytotoxic properties of an amphiphilic β-Schiff-base linked Ru(II) polypyridyl–porphyrin conjugate

    International Nuclear Information System (INIS)

    Ke, Hanzhong; Ma, Wanpeng; Wang, Hongda; Cheng, Guoe; Yuan, Han; Wong, Wai-Kwok; Kwong, Daniel W.J.; Tam, Hoi-Lam; Cheah, Kok-Wai; Chan, Chi-Fai; Wong, Ka-Leung

    2014-01-01

    A novel porphyrin–polypyridyl ruthenium(II) conjugate (TPP–Ru), in which the ruthenium(II) polypyridyl moiety is linked to the β-position of the tetraphenylporphyrin via a Schiff base linkage, has been synthesized and characterized by 1 H NMR, HRMS and UV–visible spectroscopy. The relative singlet oxygen quantum yield and two-photon absorption cross-section of this conjugate, together with its photo-induced DNA cleavage and cytotoxic activities were measured. The results show that the amphiphilic ruthenium(II) polypyridyl–porphyrin conjugate is an effective DNA photocleavage agent, with potential application in one- and two-photon absorption anti-cancer photodynamic therapy. - Highlights: • New porphyrin–ruthenium(II) polypyridyl complexes (TTP–Ru) have been synthesized. • The TTP–Ru shows substantial two-photon absorption cross-section (σ 2 =391 GM). • The TTP–Ru exhibits a substantial 1 O 2 quantum yield (0.64±0.13). • The TTP–Ru exhibits a strong DNA cleavage activity upon photo-excitation. • The TTP–Ru is available for in vitro imaging and as a photodynamic therapy agent

  12. Synthesis, singlet-oxygen photogeneration, two-photon absorption, photo-induced DNA cleavage and cytotoxic properties of an amphiphilic β-Schiff-base linked Ru(II) polypyridyl–porphyrin conjugate

    Energy Technology Data Exchange (ETDEWEB)

    Ke, Hanzhong, E-mail: kehanz@163.com [Faculty of Material Science and Chemistry, China University of Geosciences, Wuhan, Hubei 430074 (China); Ma, Wanpeng; Wang, Hongda; Cheng, Guoe [Faculty of Material Science and Chemistry, China University of Geosciences, Wuhan, Hubei 430074 (China); Yuan, Han [Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR (China); Wong, Wai-Kwok, E-mail: wkwong@hkbu.edu.hk [Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR (China); Institute of Advanced Materials, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR (China); Kwong, Daniel W.J. [Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR (China); Tam, Hoi-Lam; Cheah, Kok-Wai [Department of Physics, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR (China); Institute of Advanced Materials, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR (China); Chan, Chi-Fai; Wong, Ka-Leung [Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR (China)

    2014-10-15

    A novel porphyrin–polypyridyl ruthenium(II) conjugate (TPP–Ru), in which the ruthenium(II) polypyridyl moiety is linked to the β-position of the tetraphenylporphyrin via a Schiff base linkage, has been synthesized and characterized by {sup 1}H NMR, HRMS and UV–visible spectroscopy. The relative singlet oxygen quantum yield and two-photon absorption cross-section of this conjugate, together with its photo-induced DNA cleavage and cytotoxic activities were measured. The results show that the amphiphilic ruthenium(II) polypyridyl–porphyrin conjugate is an effective DNA photocleavage agent, with potential application in one- and two-photon absorption anti-cancer photodynamic therapy. - Highlights: • New porphyrin–ruthenium(II) polypyridyl complexes (TTP–Ru) have been synthesized. • The TTP–Ru shows substantial two-photon absorption cross-section (σ{sub 2}=391 GM). • The TTP–Ru exhibits a substantial {sup 1}O{sub 2} quantum yield (0.64±0.13). • The TTP–Ru exhibits a strong DNA cleavage activity upon photo-excitation. • The TTP–Ru is available for in vitro imaging and as a photodynamic therapy agent.

  13. Synthesis and Characterization of Protein-Conjugated Silver Nanoparticles/Silver Salt Loaded Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) Film for Prevention of Bacterial Infections and Potential Use in Bone Tissue Engineering Applications

    Science.gov (United States)

    Bakare, Rotimi Ayotunde

    Failure of orthopedic implants due to bacterial infection has been a major concern in bone tissue engineering. To this end, we have formulated a potential orthopedic implant made of naturally occurring biodegradable polymer, i.e. poly (3-hydroxylbutyrate-co-3-hydroxylvalerate) (PHBV), modified with BSA conjugated silver nanoparticles and or silver chloride. Upon release of Ag NPs and or Ag+ in the implant region, can promote aseptic environment by inhibition of bacteria growth and also support/maintain bone cell adhesion, growth, and proliferation. For formulating nanoparticles loaded PHBV scaffold, we exploit specific interaction between bovine serum albumin (BSA) of BSA capped silver nanoparticles and collagen of collagen immobilized PHBV scaffold. Therefore, the first part of this study dealt with synthesis and characterization of collagen immobilized PHBV film for loading of BSA stabilized silver (Ag/BSA) nanoparticles. Two different approaches were used to immobilize collagen on macroporous PHBV film. First approach uses thermal radical copolymerization with 2-hydroxyethylmethacrylate (HEMA), while the second approach uses aminolysis to functionalize macroporous PHBV film. Using collagen crosslinker, type I collagen was covalently grafted to formulate collagen immobilized PHEMA-g-PHBV and collagen immobilized NH2-PHBV films, respectively. Spectroscopic (FTIR, XPS), physical (SEM), and thermal (TGA) techniques were used to characterize the functionalized PHBV films. The Ag/BSA nanoparticles were then loaded on collagen immobilized PHBV films and untreated PHBV films. The concentration of nanoparticles loaded on PHBV film was determined by atomic absorption spectrometry and fluorescence spectroscopy. The amount of nanoparticles loaded on collagen immobilized PHBV film was found to be significantly greater than that on untreated PHBV film. The amount of Ag/BSA nanoparticles loaded on collagen immobilized PHBV film was found to depend on the concentration of Ag

  14. DNA-templated antibody conjugation for targeted drug delivery to cancer cells

    DEFF Research Database (Denmark)

    Liu, Tianqiang

    2016-01-01

    conjugation strategy. Recently, a site-selective antibody conjugation method called “DNA-templated protein conjugation (DTPC)” was developed by our group. The site-selective covalently attachment of single-stranded DNA (ssDNA) to proteins was achieved by using a metal-affinity DNA probe and DNA-templated...... state to get a good pharmacological performance. Recombinant antibody engineering with non-natural amino acids, or enzyme-mediated conjugation approaches (transglutaminase, Sortase A or endoglycosidase) have been reported for producing homogeneous antibody conjugates. However, these methods require...... organic synthesis due to the wide existence of the 3-histidine cluster in most wild-type proteins. In this thesis, three projects that relate to targeted drug delivery to cancer cells based on the DTPC method is described. The first project was a delivery system which uses transferrin as the targeting...

  15. A palladium-catalysed multicomponent coupling approach to conjugated poly(1,3-dipoles) and polyheterocycles

    OpenAIRE

    Leitch, David C.; Kayser, Laure V.; Han, Zhi-Yong; Siamaki, Ali R.; Keyzer, Evan N.; Gefen, Ashley; Arndtsen, Bruce A.

    2015-01-01

    Conjugated polymers have emerged over the past several decades as key components for a range of applications, including semiconductors, molecular wires, sensors, light switchable transistors and OLEDs. Nevertheless, the construction of many such polymers, especially highly substituted variants, typically involves a multistep synthesis. This can limit the ability to both access and tune polymer structures for desired properties. Here we show an alternative approach to synthesize conjugated mat...

  16. Enzymatic degradation behavior and cytocompatibility of silk fibroin-starch-chitosan conjugate membranes

    Energy Technology Data Exchange (ETDEWEB)

    Baran, Erkan T., E-mail: erkantur@metu.edu.tr; Tuzlakoglu, Kadriye, E-mail: kadriye@dep.uminho.pt; Mano, Joao F., E-mail: jmano@dep.uminho.pt; Reis, Rui L., E-mail: rgreis@dep.uminho.pt

    2012-08-01

    The objective of this study was to investigate the influence of silk fibroin and oxidized starch conjugation on the enzymatic degradation behavior and the cytocompatability of chitosan based biomaterials. The tensile stress of conjugate membranes, which was at 50 Megapascal (MPa) for the lowest fibroin and starch composition (10 weight percent (wt.%)), was decreased significantly with the increased content of fibroin and starch. The weight loss of conjugates in {alpha}-amylase was more notable when the starch concentration was the highest at 30 wt.%. The conjugates were resistant to the degradation by protease and lysozyme except for the conjugates with the lowest starch concentration. After 10 days of cell culture, the proliferation of osteoblast-like cells (SaOS-2) was stimulated significantly by higher fibroin compositions and the DNA synthesis on the conjugate with the highest fibroin (30 wt.%) was about two times more compared to the native chitosan. The light microscopy and the image analysis results showed that the cell area and the lengths were decreased significantly with higher fibroin/chitosan ratio. The study proved that the conjugation of fibroin and starch with the chitosan based biomaterials by the use of non-toxic reductive alkylation crosslinking significantly improved the cytocompatibility and modulated the biodegradation, respectively. - Highlights: Black-Right-Pointing-Pointer Silk fibroin, starch and chitosan conjugates were prepared by reductive alkylation. Black-Right-Pointing-Pointer The enzymatic biodegradation and the cytocompatibility of conjugates were tested. Black-Right-Pointing-Pointer The conjugate with 30% starch composition was degraded by {alpha}-amylase significantly. Black-Right-Pointing-Pointer Higher starch composition in conjugates prevented protease and lysozyme degradation. Black-Right-Pointing-Pointer Fibroin incorporation effectively increased the cell proliferation of conjugates.

  17. Electrochromic in conjugated polymers

    International Nuclear Information System (INIS)

    Picado Valenzuela, Alfredo

    2007-01-01

    This revision considered object the description of one of the materials with the greatest potential in the field of electrochromic (mainly in the visible region): the conjugated polymers (CP), area of enormous potential both now and in a short time ahead. The CP are insulating materials and organic semiconductors in a state not doped. They can be doped positively or negatively being observed a significant increase in the conductivity and being generated a color change in these materials. The understanding of how optical properties vary based on the chemical structure of the polymer or its mixtures and more precisely of the alternatives that can be entered into the conjugated system or π system to obtain a material that besides to be flexible, environmentally stable, presents the colored states. The revision was centred chiefly in the polypyrrole (Ppy), the polythiophene (PTh) and their derivatives such as poly (3.4-ethylenedioxythiophene) (PEDOT). The advantage of using monomers with variable structure, to adjust the composition of the copolymer, or to blend with the PC, allows to obtain a variety of colored states that can be modulated through the visible spectrum and even with applications to wavelengths outside of this region. Because the PC presented at least two different colored states can be varied continuously as a function of the voltage applied. In some cases, they may submit multicoloured statements, which offers a range of possibilities for their application in flexible electronic devices type screens and windows. Applications include smart windows, camouflage clothing and data screens. This type of material is emerging as one of the substitutes of the traditional inorganic semiconductor, with the advantage of its low cost, high flexibility and the possibility to generate multiple colors through the handling of the monomers in the structure and control of energy of his band gap. (author) [es

  18. Generalized conjugate gradient squared

    Energy Technology Data Exchange (ETDEWEB)

    Fokkema, D.R.; Sleijpen, G.L.G. [Utrecht Univ. (Netherlands)

    1994-12-31

    In order to solve non-symmetric linear systems of equations, the Conjugate Gradient Squared (CGS) is a well-known and widely used iterative method. In practice the method converges fast, often twice as fast as the Bi-Conjugate Gradient method. This is what you may expect, since CGS uses the square of the BiCG polynomial. However, CGS may suffer from its erratic convergence behavior. The method may diverge or the approximate solution may be inaccurate. BiCGSTAB uses the BiCG polynomial and a product of linear factors in an attempt to smoothen the convergence. In many cases, this has proven to be very effective. Unfortunately, the convergence of BiCGSTAB may stall when a linear factor (nearly) degenerates. BiCGstab({ell}) is designed to overcome this degeneration of linear factors. It generalizes BiCGSTAB and uses both the BiCG polynomial and a product of higher order factors. Still, CGS may converge faster than BiCGSTAB or BiCGstab({ell}). So instead of using a product of linear or higher order factors, it may be worthwhile to look for other polynomials. Since the BiCG polynomial is based on a three term recursion, a natural choice would be a polynomial based on another three term recursion. Possibly, a suitable choice of recursion coefficients would result in method that converges faster or as fast as CGS, but less erratic. It turns out that an algorithm for such a method can easily be formulated. One particular choice for the recursion coefficients leads to CGS. Therefore one could call this algorithm generalized CGS. Another choice for the recursion coefficients leads to BiCGSTAB. It is therefore possible to mix linear factors and some polynomial based on a three term recursion. This way one may get the best of both worlds. The authors will report on their findings.

  19. Reciprocity and conjugation fidelity in double phase conjugate mirrors

    Science.gov (United States)

    Delaye, Philippe; Fotiadi, Andrei A.; Roosen, Gerald

    1999-09-01

    It is well known that the conservation of energy in an optical system can be described by an invariant (intensity of the optical wave) during propagation. We identically show that reciprocity can be described by an invariant. This invariant is the overlap integral of two counterpropagating waves, that stays constant in every place of a reciprocal optical system. Applied to the double phase conjugate mirror (DPCM) this invariant can be rewritten as an equality between the ratio of the conjugation fidelity of the two ports of the DPCM and the ratio of the transmission in intensity of the two beams. If restricted to a plane wave case this relation becomes the well known equality of the diffraction efficiencies in both directions. We have implemented an experimental set-up that allows to show that the double phase conjugate mirror is reciprocal what confirms all the above discussion. We use the same set-up to measure the conjugation fidelity of the DPCM.

  20. Sequential measurements of conjugate observables

    Energy Technology Data Exchange (ETDEWEB)

    Carmeli, Claudio [Dipartimento di Fisica, Universita di Genova, Via Dodecaneso 33, 16146 Genova (Italy); Heinosaari, Teiko [Department of Physics and Astronomy, Turku Centre for Quantum Physics, University of Turku, 20014 Turku (Finland); Toigo, Alessandro, E-mail: claudio.carmeli@gmail.com, E-mail: teiko.heinosaari@utu.fi, E-mail: alessandro.toigo@polimi.it [Dipartimento di Matematica ' Francesco Brioschi' , Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

    2011-07-15

    We present a unified treatment of sequential measurements of two conjugate observables. Our approach is to derive a mathematical structure theorem for all the relevant covariant instruments. As a consequence of this result, we show that every Weyl-Heisenberg covariant observable can be implemented as a sequential measurement of two conjugate observables. This method is applicable both in finite- and infinite-dimensional Hilbert spaces, therefore covering sequential spin component measurements as well as position-momentum sequential measurements.

  1. Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6-β-D-Galp-(1–>4-β-D-GlcpNAc-(1–>3-β-D-Galp-(1–>4-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

    Directory of Open Access Journals (Sweden)

    Andreas Sundgren

    2010-07-01

    Full Text Available Background: In bacteria with truncated lipopolysaccharide structures, i.e., lacking the O-antigen polysaccharide part, core structures are exposed to the immune system upon infection and thus their use as carbohydrate surface antigens in glycoconjugate vaccines can be considered and investigated. One such suggested structure from Haemophilus influenzae LPS is the phosphorylated pentasaccharide 6-PEtN-α-D-GalpNAc-(1→6-β-D-Galp-(1→4-β-D-GlcpNAc-(1→3-β-D-Galp-(1→4-β-D-Glcp.Results: Starting from a spacer-containing lactose derivative a suitably protected lacto-N-neotetraose tetrasaccharide structure was constructed through subsequential couplings with two thioglycoside donors, a glucosamine residue followed by a galactose derivative, using NIS/AgOTf as promoter. Removal of a silyl protecting group at the primary position of the non-reducing end residue afforded an acceptor to which the terminal α-galactosamine moiety was introduced using a 2-azido bromo sugar and halide assisted coupling conditions. Global deprotection afforded the non-phosphorylated target pentasaccharide, whereas removal of a silyl group from the primary position of the non-reducing end residue produced a free hydroxy group which was phosphorylated using H-phosphonate chemistry to yield the phosphoethanolamine-containing protected pentasaccharide. Partial deprotection afforded the phosphorylated target pentasaccharide with a free spacer amino group but with a protected phosphoethanolamino group. Conjugation of the spacer amino group to biotin or dimethyl squarate followed by deprotection of the phosphoethanolamino group and, in the case of the squarate derivative, further reaction with a protein then afforded the title conjugates.Conclusion: An effective synthesis of a biologically interesting pentasaccharide structure has been accomplished. The target pentasaccharide, an α-GalNAc substituted lacto-N-neotetraose structure, comprises a phosphoethanolamine motif and

  2. Protein carriers of conjugate vaccines

    Science.gov (United States)

    Pichichero, Michael E

    2013-01-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

  3. Enantioselective synthesis of possible diastereomers of heptadeca-1-ene-4,6-diyne-3,8,9,10-tetrol; putative structure of a conjugated diyne natural product isolated from Hydrocotyle leucocephala.

    Science.gov (United States)

    Prasad, Kavirayani R; Swain, Bandita

    2011-04-01

    Enantioselective synthesis of possible diastereomers of heptadeca-1-ene-4,6-diyne-3,8,9,10-tetrol, a structure proposed for the natural product isolated from Hydrocotyle leucocephala is accomplished. The reported spectral data of the natural product did not match those of any of the isomers that were synthesized and established that the structure proposed for the natural product is not correct and requires revision.

  4. Fullerene–biomolecule conjugates and their biomedicinal applications

    Directory of Open Access Journals (Sweden)

    Yang X

    2013-12-01

    Full Text Available Xinlin Yang,1 Ali Ebrahimi,1 Jie Li,1,2 Quanjun Cui11Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA; 2School of Materials Science, Beijing Institute of Technology, Beijing, People's Republic of ChinaAbstract: Fullerenes are among the strongest antioxidants and are characterized as "radical sponges." The research on biomedicinal applications of fullerenes has achieved significant progress since the landmark publication by Friedman et al in 1993. Fullerene–biomolecule conjugates have become an important area of research during the past 2 decades. By a thorough literature search, we attempt to update the information about the synthesis of different types of fullerene–biomolecule conjugates, including fullerene-containing amino acids and peptides, oligonucleotides, sugars, and esters. Moreover, we also discuss in this review recently reported data on the biological and pharmaceutical utilities of these compounds and some other fullerene derivatives of biomedical importance. While within the fullerene–biomolecule conjugates, in which fullerene may act as both an antioxidant and a carrier, specific targeting biomolecules conjugated to fullerene will undoubtedly strengthen the delivery of functional fullerenes to sites of clinical interest.Keywords: fullerene, amino acid, peptide, oligonucleotide, sugar, ester

  5. A new entry into the portfolio of α-glucosidase inhibitors as potent therapeutics for type 2 diabetes: Design, bioevaluation and one-pot multi-component synthesis of diamine-bridged coumarinyl oxadiazole conjugates.

    Science.gov (United States)

    Kazmi, Madiha; Zaib, Sumera; Ibrar, Aliya; Amjad, Sayyeda Tayyeba; Shafique, Zainab; Mehsud, Saifullah; Saeed, Aamer; Iqbal, Jamshed; Khan, Imtiaz

    2018-04-01

    Diabetes mellitus (DM), a chronic multifarious metabolic disorder resulting from impaired glucose homeostasis has become one of the most challenging diseases with severe life threat to public health. The inhibition of α-glucosidase, a key carbohydrate hydrolyzing enzyme, could serve as one of the effective methodology in both preventing and treating diabetes through controlling the postprandial glucose levels and suppressing postprandial hyperglycemia. In this context, three series of diamine-bridged bis-coumarinyl oxadiazole conjugates were designed and synthesized by one-pot multi-component methodology. The synthesized conjugates (4a-j, 5a-j, 6a-j) were evaluated as potential inhibitors of glucosidases. Compound 6f containing 4,4'-oxydianiline linker was identified as the lead and selective inhibitor of α-glucosidase enzyme with an IC 50 value of 0.07 ± 0.001 μM (acarbose: IC 50  = 38.2 ± 0.12 μM). This inhibition efficacy was ∼545-fold higher compared to the standard drug. Compound 6f was also emerged as the lead molecule against intestinal maltase-glucoamylase with good inhibition strength (IC 50  = 0.04 ± 0.02 μM) compared to acarbose (IC 50  = 0.06 ± 0.01 μM). Against β-glucosidase enzyme, compound 6 g was noted as the lead inhibitor with IC 50 value of 0.08 ± 0.002 μM. Michaelis-Menten kinetic experiments were performed to explore the mechanism of inhibition. Molecular docking studies of the synthesized library of hybrid structures against glucosidase enzyme were performed to describe ligand-protein interactions at molecular level that provided an insight into the biological properties of the analyzed compounds. The results suggested that the inhibitors could be stabilized in the active site through the formation of multiple interactions with catalytic residues in a cooperative fashion. In addition, strong binding interactions of the compounds with the amino acid residues were effective for the

  6. Composition-Tunable Optical Properties of Zn x Cd(1 - x)S Quantum Dot-Carboxymethylcellulose Conjugates: Towards One-Pot Green Synthesis of Multifunctional Nanoplatforms for Biomedical and Environmental Applications

    Science.gov (United States)

    Mansur, Alexandra A. P.; Mansur, Herman S.; Caires, Anderson J.; Mansur, Rafael L.; Oliveira, Luiz C.

    2017-07-01

    Quantum dots (QDs) are colloidal semiconductor nanocrystals with unique properties that can be engineered by controlling the nanoparticle size and chemical composition by doping and alloying strategies. However, due to their potential toxicity, augmenting their biocompatibility is yet a challenge for expanding to several biomedical and environmentally friendly applications. Thus, the main goal of this study was to develop composition-tunable and biocompatible Zn x Cd1 - x S QDs using carboxymethylcellulose polysaccharide as direct capping ligand via green colloidal aqueous route at neutral pH and at room temperature for potential biomedical and environmental applications. The ternary alloyed QDs were extensively characterized using UV-vis spectroscopy, photoluminescence spectroscopy (PL), transmission electron microscopy (TEM), X-ray diffraction (XRD), electron energy loss spectroscopy (EELS), and X-ray photoelectrons spectroscopy (XPS). The results indicated that Zn x Cd(1 - x)S QDs were surface stabilized by carboxymethylcellulose biopolymer with spherical morphology for all composition of alloys and narrow sizes distributions ranging from 4 to 5 nm. The XRD results indicated that monophasic ternary alloyed Zn x Cd1 - x S nanocrystals were produced with homogenous composition of the core as evidenced by EELS and XPS analyses. In addition, the absorption and emission optical properties of Zn x Cd1 - x S QDs were red shifted with increasing the amount of Cd2+ in the alloyed nanocrystals, which have also increased the quantum yield compared to pure CdS and ZnS nanoparticles. These properties of alloyed nanomaterials were interpreted based on empirical model of Vegard's law and chemical bond model (CBM). As a proof of concept, these alloyed-QD conjugates were tested for biomedical and environmental applications. The results demonstrated that they were non-toxic and effective fluorophores for bioimaging live HEK293T cells (human embryonic kidney cells) using confocal

  7. Research study of conjugate materials; Conjugate material no chosa kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    The paper reported an introductory research on possibilities of new glass `conjugate materials.` The report took up the structure and synthetic process of conjugate materials to be researched/developed, classified them according to structural elements on molecular, nanometer and cluster levels, and introduced the structures and functions. Further, as glasses with new functions to be proposed, the paper introduced transparent and high-strength glass used for houses and vehicles, light modulation glass which realizes energy saving and optical data processing, and environmentally functional glass which realizes environmental cleaning or high performance biosensor. An initial survey was also conducted on rights of intellectual property to be taken notice of in Japan and abroad in the present situation. Reports were summed up and introduced of Osaka National Research Institute, Electrotechnical Laboratory, and National Industrial Research Institute of Nagoya which are all carrying out leading studies of conjugate materials. 235 refs., 135 figs., 6 tabs.

  8. Conjugated polymer nanoparticles, methods of using, and methods of making

    KAUST Repository

    Habuchi, Satoshi

    2017-03-16

    Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.

  9. Asymmetric conjugate addition of alkylzirconium reagents to α,β-unsaturated lactones.

    Science.gov (United States)

    Maciver, Eleanor E; Maksymowicz, Rebecca M; Wilkinson, Nancy; Roth, Philippe M C; Fletcher, Stephen P

    2014-06-20

    The asymmetric synthesis of β-substituted lactones by catalytic asymmetric conjugate addition of alkyl groups to α,β-unsaturated lactones is reported. The method uses alkylzirconium nucleophiles prepared in situ from alkenes and the Schwartz reagent. Enantioselective additions to 6- and 7-membered lactones proceed at rt, tolerate a wide variety of functional groups, and are readily scalable. The method was used in a formal asymmetric synthesis of mitsugashiwalactone.

  10. Preparation of Conjugates of Cytotoxic Lupane Triterpenes with Biotin.

    Science.gov (United States)

    Soural, Miroslav; Hodon, Jiri; Dickinson, Niall J; Sidova, Veronika; Gurska, Sona; Dzubak, Petr; Hajduch, Marian; Sarek, Jan; Urban, Milan

    2015-12-16

    To better understand the mechanism of action of antitumor triterpenes, we are developing methods to identify their molecular targets. A promising method is based on combination of quantitative proteomics with SILAC and uses active compounds anchored to magnetic beads via biotin-streptavidin interaction. We developed a simple and fast solid-phase synthetic technique to connect terpenes to biotin through a linker. Betulinic acid was biotinylated from three different conjugation sites for use as a standard validation tool since many molecular targets of this triterpene are already known. Then, a set of four other cytotoxic triterpenoids was biotinylated. Biotinylated terpenes were similarly cytotoxic to their nonbiotinylated parents, which suggests that the target identification should not be influenced by linker or biotin. The developed solid-phase synthetic approach is the first attempt to use solid-phase synthesis to connect active triterpenes to biotin and is applicable as a general procedure for routine conjugation of triterpenes with other molecules of choice.

  11. Toward anticancer immunotherapeutics: well-defined polymer-antibody conjugates for selective dendritic cell targeting.

    Science.gov (United States)

    Tappertzhofen, Kristof; Bednarczyk, Monika; Koynov, Kaloian; Bros, Matthias; Grabbe, Stephan; Zentel, Rudolf

    2014-10-01

    This paper describes the synthesis of semitelechelic maleimide-modified N-(2-hydroxypropyl)methacrylamid) (HPMA) based polymers of narrow dispersity that can be conjugated e.g. to anti-DEC-205 antibodies affording "star-like" topologies (one antibody decorated with several polymer chains). FCS revealed a hydrodynamic diameter of R(h)  = 7.9 nm and SEC narrow dispersity (1.45). Primary in vitro studies with bone marrow derived dendritic cells (DC) show higher cellular binding and uptake rates compared to control samples. Moreover, incubating these conjugates to primary splenocytes demonstrates a much higher affinity to the primary DCs than to any other immune cell population within the spleen. This differentiation is, thereby, much more pronounced for the star-like conjugates than for conjugates made from polymers statistically modified with anti-DEC-205. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Antibody Drug Conjugates: Preclinical Considerations.

    Science.gov (United States)

    Bornstein, Gadi G

    2015-05-01

    The development path for antibody drug conjugates (ADCs) is more complex and challenging than for unmodified antibodies. While many of the preclinical considerations for both unmodified and antibody drug conjugates are shared, special considerations must be taken into account when developing an ADC. Unlike unmodified antibodies, an ADC must preferentially bind to tumor cells, internalize, and traffic to the appropriate intracellular compartment to release the payload. Parameters that can impact the pharmacological properties of this class of therapeutics include the selection of the payload, the type of linker, and the methodology for payload drug conjugation. Despite a plethora of in vitro assays and in vivo models to screen and evaluate ADCs, the challenge remains to develop improved preclinical tools that will be more predictive of clinical outcome. This review will focus on preclinical considerations for clinically validated small molecule ADCs. In addition, the lessons learned from Mylotarg®, the first in class FDA-approved ADC, are highlighted.

  13. Persistence Mechanisms of Conjugative Plasmids

    DEFF Research Database (Denmark)

    Bahl, Martin Iain; Hansen, Lars H.; Sørensen, Søren Johannes

    2009-01-01

    maintenance in the host cell. These importantly include the ability to self-mobilize in a process termed conjugative transfer, which may occur across species barriers. Other plasmid stabilizing mechanisms include the multimer resolution system, active partitioning, and post-segregational-killing of plasmid......Are plasmids selfish parasitic DNA molecules or an integrated part of the bacterial genome? This chapter reviews the current understanding of the persistence mechanisms of conjugative plasmids harbored by bacterial cells and populations. The diversity and intricacy of mechanisms affecting...... the successful propagation and long-term continued existence of these extra-chromosomal elements is extensive. Apart from the accessory genetic elements that may provide plasmid-harboring cells a selective advantage, special focus is placed on the mechanisms conjugative plasmids employ to ensure their stable...

  14. Conjugated ionomers for photovoltaic applications: electric field driven charge separation in organic photovoltaics. Final Technical report

    Energy Technology Data Exchange (ETDEWEB)

    Lonergan, Mark [Univ. of Oregon, Eugene, OR (United States)

    2015-05-29

    Final technical report for Conjugated ionomers for photovoltaic applications, electric field driven charge separation in organic photovoltaics. The central goal of the work we completed was been to understand the photochemical and photovoltaic properties of ionically functionalized conjugated polymers (conjugated ionomers or polyelectrolytes) and energy conversion systems based on them. We primarily studied two classes of conjugated polymer interfaces that we developed based either upon undoped conjugated polymers with an asymmetry in ionic composition (the ionic junction) or doped conjugated polymers with an asymmetry in doping type (the p-n junction). The materials used for these studies have primarily been the polyacetylene ionomers. We completed a detailed study of p-n junctions with systematically varying dopant density, photochemical creation of doped junctions, and experimental and theoretical work on charge transport and injection in polyacetylene ionomers. We have also completed related work on the use of conjugated ionomers as interlayers that improve the efficiency or organic photovoltaic systems and studied several important aspects of the chemistry of ionically functionalized semiconductors, including mechanisms of so-called "anion-doping", the formation of charge transfer complexes with oxygen, and the synthesis of new polyfluorene polyelectrolytes. We also worked worked with the Haley group at the University of Oregon on new indenofluorene-based organic acceptors.

  15. Synthetic Nucleic Acid Analogues in Gene Therapy: An Update for Peptide–Oligonucleotide Conjugates

    DEFF Research Database (Denmark)

    Taskova, Maria; Mantsiou, Anna; Astakhova, Kira

    2017-01-01

    The main objective of this work is to provide an update on synthetic nucleic acid analogues and nanoassemblies as tools in gene therapy. In particular, the synthesis and properties of peptide–oligonucleotide conjugates (POCs), which have high potential in research and as therapeutics, are described...

  16. Phase conjugation of acoustic beams

    Science.gov (United States)

    Bunkin, F. V.; Vlasov, D. V.; Kravtsov, Iu. A.

    The paper presents a classification of methods for the phase conjugation (PC) of wave fields of various physical natures on the basis of such nonliner interactions as stimulated scattering, and three- and four-wave interactions. Among the latter, attention is given to holographic (volume and surface) and parametric PC schemes, permitting PC with amplification. The possibility of developing phase-conjugated devices using acoustic PC devices on the basis of various nonlinear effects is considered. Experimental results pertaining to the PC of sound fields are presented, and possible applications of acoustic PC devices are indicated.

  17. Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon.

    Science.gov (United States)

    Liu, Mingjuan; Hummer, B Timothy; Li, Xiaoling; Hassel, Bret A

    2004-11-01

    Interferon (IFN)-stimulated gene (15 kDa) (ISG15) is a ubiquitin-like protein that forms covalent conjugates with cellular proteins. ISG15 is induced by IFN, microbial challenge, and p53, suggesting that it represents a genetic response that is shared among diverse stress stimuli. To investigate the regulation of this posttranslational modification pathway by a genotoxic chemotherapeutic agent, we examined ISG15 induction and conjugation in cells treated with the topoisomerase I (topoI) poison, camptothecin (CPT). CPT induced ISG15mRNA, and induction required protein synthesis and a functional p53 protein. However, IFN and the Jak-Stat components of the IFN signaling pathway were dispensable for CPT induction of ISG15. CPT induced free ISG15 and conjugates in a dose-dependent and time-dependent manner. A single 55-kDa protein was the prominent CPT-induced ISG15 conjugate and localized to the nuclear compartment. CPT-induced ISG15 conjugates were distinct from those induced by IFN; however, CPT treatment dramatically enhanced ISG15 conjugation in response to IFN. These findings provide the first evidence of a stimulus-specific induction of discrete ISG15 conjugate species and demonstrate that treatment with a combination of cancer therapeutic agents can cooperate to enhance ISG15 conjugation. Identification of the specific ISG15 conjugates induced by chemotherapeutic agents may reveal novel molecular targets.

  18. Direct heteroarylation polymerization: guidelines for defect-free conjugated polymers.

    Science.gov (United States)

    Bura, Thomas; Beaupré, Serge; Légaré, Marc-André; Quinn, Jesse; Rochette, Etienne; Blaskovits, J Terence; Fontaine, Frédéric-Georges; Pron, Agnieszka; Li, Yuning; Leclerc, Mario

    2017-05-01

    Direct (hetero)arylation polymerization (DHAP) has emerged as a valuable and atom-economical alternative to traditional cross-coupling methods for the synthesis of low-cost and efficient conjugated polymers for organic electronics. However, when applied to the synthesis of certain (hetero)arene-based materials, a lack of C-H bond selectivity has been observed. To prevent such undesirable side-reactions, we report the design and synthesis of new, bulky, phosphine-based ligands that significantly enhance selectivity of the DHAP process for both halogenated and non-halogenated electron-rich and electron-deficient thiophene-based comonomers. To better understand the selectivity issues, density functional theory (DFT) calculations have been performed on various halogenated and non-halogenated electron-rich and electron-deficient thiophene-based comonomers. Calculations showed that the presence of bromine atoms decreases the energy of activation ( E a ) of the adjacent C-H bonds, allowing undesirable β-defects for some brominated aromatic units. Both calculations and the new ligands should lead to the rational design of monomers and methods for the preparation of defect-free conjugated polymers from DHAP.

  19. Efficient synthesis of substituted dihydrotetraazapentacenes.

    Science.gov (United States)

    Seillan, Claire; Brisset, Hugues; Siri, Olivier

    2008-09-18

    We describe a versatile and very efficient synthesis of previously unknown substituted 5,14-dihydro-5,7,12,14-tetraazapentacenes (DHTAPs). A structural study by NMR spectroscopy showed that the conjugated pi-system of the pentacyclic skeleton rearranges depending on the electronic effect of the substituent(s).

  20. High pressure structural studies of conjugated molecules

    DEFF Research Database (Denmark)

    Knaapila, Matti; Torkkeli, Mika; Scherf, Ullrich

    2018-01-01

    This chapter highlights high pressure GPa level structural studies of conjugated polymers and their analogues: conjugated oligomers and molecules, and rigid rod polymers. Attention is placed on our recent studies of polyfluorenes.......This chapter highlights high pressure GPa level structural studies of conjugated polymers and their analogues: conjugated oligomers and molecules, and rigid rod polymers. Attention is placed on our recent studies of polyfluorenes....

  1. Enhanced photophysics of conjugated polymers

    Science.gov (United States)

    Chen, Liaohai [Darien, IL

    2007-06-12

    A particulate fluorescent conjugated polymer surfactant complex and method of making and using same. The particles are between about 15 and about 50 nm and when formed from a lipsome surfactant have a charge density similar to DNA and are strongly absorbed by cancer cells.

  2. Conjugal Pairing in Escherichia Coli

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 8. Conjugal Pairing in Escherichia Coli. Joshua Lederberg. Classics Volume 13 Issue 8 August 2008 pp 793-794. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/013/08/0793-0794 ...

  3. Galois conjugates of topological phases

    Science.gov (United States)

    Freedman, M. H.; Gukelberger, J.; Hastings, M. B.; Trebst, S.; Troyer, M.; Wang, Z.

    2012-01-01

    Galois conjugation relates unitary conformal field theories and topological quantum field theories (TQFTs) to their nonunitary counterparts. Here we investigate Galois conjugates of quantum double models, such as the Levin-Wen model. While these Galois-conjugated Hamiltonians are typically non-Hermitian, we find that their ground-state wave functions still obey a generalized version of the usual code property (local operators do not act on the ground-state manifold) and hence enjoy a generalized topological protection. The key question addressed in this paper is whether such nonunitary topological phases can also appear as the ground states of Hermitian Hamiltonians. Specific attempts at constructing Hermitian Hamiltonians with these ground states lead to a loss of the code property and topological protection of the degenerate ground states. Beyond this, we rigorously prove that no local change of basis can transform the ground states of the Galois-conjugated doubled Fibonacci theory into the ground states of a topological model whose Hermitian Hamiltonian satisfies Lieb-Robinson bounds. These include all gapped local or quasilocal Hamiltonians. A similar statement holds for many other nonunitary TQFTs. One consequence is that these nonunitary TQFTs do not describe physical realizations of topological phases. In particular, this implies that the “Gaffnian” wave function can not be the ground state of a gapped fractional quantum Hall state.

  4. Conjugal Pairing in Escherichia Coli

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 8. Conjugal Pairing in Escherichia Coli. Joshua Lederberg. Classics Volume 13 Issue 8 August 2008 pp 793-794. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/013/08/0793-0794 ...

  5. Bacteriophytochromes control conjugation in Agrobacterium fabrum.

    Science.gov (United States)

    Bai, Yingnan; Rottwinkel, Gregor; Feng, Juan; Liu, Yiyao; Lamparter, Tilman

    2016-08-01

    Bacterial conjugation, the transfer of single stranded plasmid DNA from donor to recipient cell, is mediated through the type IV secretion system. We performed conjugation assays using a transmissible artificial plasmid as reporter. With this assay, conjugation in Agrobacterium fabrum was modulated by the phytochromes Agp1 and Agp2, photoreceptors that are most sensitive in the red region of visible light. In conjugation studies with wild-type donor cells carrying a pBIN-GUSINT plasmid as reporter that lacked the Ti (tumor inducing) plasmid, no conjugation was observed. When either agp1(-) or agp2(-) knockout donor strains were used, plasmid DNA was delivered to the recipient, indicating that both phytochromes suppress conjugation in the wild type donor. In the recipient strains, the loss of Agp1 or Agp2 led to diminished conjugation. When wild type cells with Ti plasmid and pBIN-GUS reporter plasmid were used as donor, a high rate of conjugation was observed. The DNA transfer was down regulated by red or far-red light by a factor of 3.5. With agp1(-) or agp2(-) knockout donor cells, conjugation in the dark was about 10 times lower than with the wild type donor, and with the double knockout donor no conjugation was observed. These results imply that the phytochrome system has evolved to inhibit conjugation in the light. The decrease of conjugation under different temperature correlated with the decrease of phytochrome autophosphorylation. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy ...

    African Journals Online (AJOL)

    REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy. AOK Johnson. Abstract. Conjugated hyperbilirubinaemia exists when the conjugated serum bilirubin level is more than 2 mg/dl or more than 20 per cent of the total serum bilirubin. It is always pathological in early infancy. The causes are many and diverse ...

  7. A physics-explicit model of bacterial conjugation shows the stabilizing role of the conjugative junction

    OpenAIRE

    Pastuszak, Jakub; Waclaw, Bartlomiej

    2017-01-01

    Conjugation is a process in which bacteria exchange DNA through a physical connection (conjugative junction) between mating cells. Despite its significance for processes such as the spread of antibiotic resistance, the role of physical forces in conjugation is poorly understood. Here we use computer models to show that the conjugative junction not only serves as a link to transfer the DNA but it also mechanically stabilises the mating pair which significantly increases the conjugation rate. W...

  8. TAT Peptide and Its Conjugates: Proteolytic Stability

    OpenAIRE

    Grunwald, Jacob; Rejtar, Tomas; Sawant, Rupa; Wang, Zhouxi; Torchilin, Vladimir P.

    2009-01-01

    The proteolytic cleavage of TATp, TATp-PEG1000-PE conjugate (TATp-conjugate), and TATp as TATp-conjugate in mixed micelles made of TATp-conjugate and PEG5000-PE (2.5% mol of TATp-conjugate, TATp-Mic) were studied by HPLC with fluorescent detection using fluorenylmethyl chloroformate (FMOC) labeling and by MALDI-TOF MS analysis. The cleavage kinetics were analyzed in human blood plasma and in trypsin-containing phosphate buffered saline (PBS), pH 7.4, to simulate the proteolytic activity of hu...

  9. Cytotoxic conjugates of betulinic acid and substituted triazoles prepared by Huisgen Cycloaddition from 30-azidoderivatives.

    Directory of Open Access Journals (Sweden)

    Veronika Sidova

    Full Text Available In this work, we describe synthesis of conjugates of betulinic acid with substituted triazoles prepared via Huisgen 1,3-cycloaddition. All compounds contain free 28-COOH group. Allylic bromination of protected betulinic acid by NBS gave corresponding 30-bromoderivatives, their substitution with sodium azides produced 30-azidoderivatives and these azides were subjected to CuI catalysed Huisgen 1,3-cycloaddition to give the final conjugates. Reactions had moderate to high yields. All new compounds were tested for their in vitro cytotoxic activities on eight cancer and two non-cancer cell lines. The most active compounds were conjugates of 3β-O-acetylbetulinic acid and among them, conjugate with triazole substituted by benzaldehyde 9b was the best with IC50 of 3.3 μM and therapeutic index of 9.1. Five compounds in this study had IC50 below 10 μM and inhibited DNA and RNA synthesis and caused block in G0/G1 cell cycle phase which is highly similar to actinomycin D. It is unusual that here prepared 3β-O-acetates were more active than compounds with the free 3-OH group and this suggests that this set may have common mechanism of action that is different from the mechanism of action of previously known 3β-O-acetoxybetulinic acid derivatives. Benzaldehyde type conjugate 9b is the best candidate for further drug development.

  10. Cytotoxic conjugates of betulinic acid and substituted triazoles prepared by Huisgen Cycloaddition from 30-azidoderivatives

    Science.gov (United States)

    Sidova, Veronika; Zoufaly, Pavel; Pokorny, Jan; Dzubak, Petr; Hajduch, Marian; Popa, Igor

    2017-01-01

    In this work, we describe synthesis of conjugates of betulinic acid with substituted triazoles prepared via Huisgen 1,3-cycloaddition. All compounds contain free 28-COOH group. Allylic bromination of protected betulinic acid by NBS gave corresponding 30-bromoderivatives, their substitution with sodium azides produced 30-azidoderivatives and these azides were subjected to CuI catalysed Huisgen 1,3-cycloaddition to give the final conjugates. Reactions had moderate to high yields. All new compounds were tested for their in vitro cytotoxic activities on eight cancer and two non-cancer cell lines. The most active compounds were conjugates of 3β-O-acetylbetulinic acid and among them, conjugate with triazole substituted by benzaldehyde 9b was the best with IC50 of 3.3 μM and therapeutic index of 9.1. Five compounds in this study had IC50 below 10 μM and inhibited DNA and RNA synthesis and caused block in G0/G1 cell cycle phase which is highly similar to actinomycin D. It is unusual that here prepared 3β-O-acetates were more active than compounds with the free 3-OH group and this suggests that this set may have common mechanism of action that is different from the mechanism of action of previously known 3β-O-acetoxybetulinic acid derivatives. Benzaldehyde type conjugate 9b is the best candidate for further drug development. PMID:28158265

  11. Synthesis and Characterization of BSA Conjugated Silver Nanoparticles (Ag/BSA Nanoparticles) and Evaluation of Biological Properties of Ag/BSA Nanoparticles and Ag/BSA Nanoparticles Loaded Poly(hydroxy butyrate valerate) PHBV Films

    Science.gov (United States)

    Ambaye, Almaz

    Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa are the etiological agents of several infectious diseases. Antibiotic resistance by these three microbes has emerged as a prevalent problem due in part to the misuse of existing antibiotics and the lack of novel antibiotics. Nanoparticles have emerged as an alternative antibacterial agents to conventional antibiotics owing to their high surface area to volume ratio and their unique chemical and physical properties. Among the nanoparticles, silver nanoparticles have gained increasing attention because silver nanoparticles exhibit antibacterial activity against a range of gram positive and gram negative bacteria. Nanoparticles of well-defined chemistry and morphology can be used in broad biomedical applications, especially in bone tissue engineering applications, where bone infection by bacteria can be acute and lethal. It is commonly noted in the literature that the activity of nanoparticles against microorganisms is dependent upon the size and concentration of the nanoparticles as well as the chemistry of stabilizing agent. To the best of our knowledge, a comprehensive study that evaluates the antibacterial activity of well characterized silver nanoparticles in particular Bovine Serum Albumin (BSA) stabilized against S. aureus and E. coli and cytotoxicity level of BSA stabilized silver nanoparticles towards osteoblast cells (MC3T3-E1) is currently lacking. Therefore, the primary objective of this study was to characterize protein conjugated silver nanoparticles prepared by chemical reduction of AgNO3 and BSA mixture. The formation of Ag/BSA nanoparticles was studied by UV-Vis spectroscopy. The molar ratio of silver to BSA in the Ag/BSA nanoparticles was established to be 27+/- 3: 1, based on Thermogravimetric Analysis and Atomic Absorption Spectroscopy. Based on atomic force microscopy, dynamic light scattering,and transmission electron microscopy(TEM) measurements, the particle size (diameter) of

  12. Lipophilic Muramyl Dipeptide-Antigen Conjugates as Immunostimulating Agents.

    Science.gov (United States)

    Willems, Marian M J H P; Zom, Gijs G; Meeuwenoord, Nico; Khan, Selina; Ossendorp, Ferry; Overkleeft, Herman S; van der Marel, Gijsbert A; Filippov, Dmitri V; Codée, Jeroen D C

    2016-01-19

    Muramyl dipeptide (MDP) is the smallest peptidoglycan fragment capable of triggering the innate immune system through interaction with the intracellular NOD2 receptor. To develop synthetic vaccine modalities composed of an antigenic entity (typically a small peptide) and a molecular adjuvant with well-defined activity, we previously assembled covalent MDP-antigen conjugates. Although these were found to be capable of stimulating the NOD2 receptor and were processed by dendritic cells (DCs) leading to effective antigen presentation, DC maturation--required for an apt immune response--could not be achieved with these conjugates. To improve the efficacy of these vaccine modalities, we equipped the MDP moiety with lipophilic tails, well-known modifications to enhance the immune-stimulatory activity of MDPs. Herein we report the design and synthesis of a lipophilic MDP-antigen conjugate and show that it is a promising vaccine modality capable of stimulating the NOD2 receptor, maturing DCs, and delivering antigen cargo into the MHC-I cross-presentation pathway. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Synthesis of Novel π-Conjugated Rod-Rod-Rod Triblock Copolymers Containing Poly(3-hexylthiophene and Polyacetylene Segments by Combination of Quasi-Living GRIM and Living Anionic Polymerization

    Directory of Open Access Journals (Sweden)

    Tomoya Higashihara

    2011-01-01

    Full Text Available The first successful synthesis of a new rod-rod-rod triblock copolymer, polyacetylene(PA-b-poly(3-hexylthiophene(P3HT-b-PA could be synthesized by a combination of quasi-living Grignard metathesis (GRIM and living anionic polymerization. We first confirmed that poly(4-tolyl vinyl sulfoxide (PTVS, which is a soluble precursor for PA, could be synthesized by living anionic polymerization in THF at −78 °C, initiated with 3-methyl-1,1-diphenylpentyllithium as the initiator in the presence of in situ-generated lithium enolate. The molecular weights (MWs and polydispersities (PDIs were well controlled (MW = 5,200–27,000, PDI = 1.10–1.22, respectively. A coil-rod-coil triblock copolymer, PTVS-b-P3HT-b-PTVS, (6,000-12,500-6,000 could also be synthesized, initiated with a P3HT-based difunctional macroinitiator in the presence of lithium enolate. GPC-RALLS and 1H NMR analyses confirmed a high degree of structural homogeneity of PTVS-b-P3HT-b-PTVS. A thermal transformation reaction of the polymer was carried out in the film state at 170 °C for 2 h to afford PA-b-P3HT-b-PA quantitatively, as monitored by TGA and FT-IR analyses. The optical and electronic properties as well as the morphological behavior of the block copolymers were investigated by UV-vis spectroscopy, conductivity measurement, and AFM observation.

  14. Synthesis and evaluation of {sup 99m}Tc-labeled folate-tripeptide conjugate as a folate receptor-targeeted imaging agent in a tumor-bearing mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Myoung Hyoun; Kim, Chang Guhn; Kim, Dae Weung [Dept. of Nuclear Medicine, Wonkwang University School of Medicine, Iksan (Korea, Republic of); Kim, Woo Hyoung [Dept. of Nuclear Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-09-15

    The folate receptor (FR) is an attractive molecular target since it is overexpressed in a variety of human tumors. The purpose of the present study was to synthesize and evaluate the feasibility of a novel {sup 99m}Tc-ECG-EDA (Glu-Cys-Gly-ethylenediamine)-folate as an FR-positive tumor imaging agent in a mouse tumor model. ECG-EDA-folate was synthesized using solid phase peptide synthesis (SPPS) and radiolabeled with {sup 99m}Tc using tripeptide ECG as a chelator. FR-positive KB cells were inoculated in athymic nude mice. Following injection of {sup 99m}Tc-ECG-EDA-folate, serial scintigraphy and micro-SPECT/CT imaging were performed at various time points with and without pre-administration of excess free folate. Mean count densities (MCD) for regions of interest drawn on KB tumors and major normal organs at each time point were measured, and uptake ratios of tumor to normal organs were calculated. ECG-EDA-folate was labeled with {sup 99m}Tc with high radiolabeling efficiency and stability (>96 %). FR-positive tumors were clearly visualized on both scintigraphy and micro-SPECT/CT images and the tumor uptake of {sup 99m}Tc-ECG-EDA-folate was markedly suppressed with faint visualization of tumors by pre-administration of excess free folate on serial planar scintigraphy, indicating FR-specific binding of the agent. Furthermore, semiquantitative analysis of MCD data showed again that both tumor MCD and tumor-to-normal organ ratios decreased considerably by pre-administration of excess free folate, supporting FR-specific tumor uptake. Tumor-to-normal organ ratios approximately increased with time after injection until 4 h. The present study demonstrated that 9{sup 99m}Tc-ECG-EDA-folate can bind specifically to FR with clear visualization of FR-positive tumors in a mouse tumor model.

  15. A Green Route to Conjugated Polyelectrolyte Interlayers for High-Performance Solar Cells.

    Science.gov (United States)

    Subbiah, Jegadesan; Mitchell, Valerie D; Hui, Nicholas K C; Jones, David J; Wong, Wallace W H

    2017-07-10

    Synthesis of fluorene-based conjugated polyelectrolytes was achieved via Suzuki polycondensation in water and completely open to air. The polyelectrolytes were conveniently purified by dialysis and analysis of the materials showed properties expected for fluorene-based conjugated polyelectrolytes. The materials were then employed in solar cell devices as an interlayer in conjunction with ZnO. The double interlayer led to enhanced power conversion efficiency of 10.75 % and 15.1 % for polymer and perovskite solar cells, respectively. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Solid-Phase Synthesis for the Construction of Biologically Interesting Molecules and the Total Synthesis of Trioxacarcin DC-45-A2

    DEFF Research Database (Denmark)

    Mikkelsen, Remi Jacob Thomsen

    . Furthermore a route to another key building block was developed featuring a Stille cross-coupling.Synthesis of Poly-fused Heterocycles. In the search for new biologically active compounds a methodology for the synthesis of polyfused heterocycles was investigated. This led to the development and optimization...... of a key aldol condensation/conjugate addition sequence for the synthesis of poly-fused heterocycles....

  17. Modelling conjugation with stochastic differential equations.

    Science.gov (United States)

    Philipsen, K R; Christiansen, L E; Hasman, H; Madsen, H

    2010-03-07

    Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two Enterococcus faecium strains in a rich exhaustible media. The model contains a new expression for a substrate dependent conjugation rate. A maximum likelihood based method is used to estimate the model parameters. Different models including different noise structure for the system and observations are compared using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared to the model without plate conjugation. The modelling approach described in this article can be applied generally when modelling dynamical systems. 2009 Elsevier Ltd. All rights reserved.

  18. The Tcp conjugation system of Clostridium perfringens.

    Science.gov (United States)

    Wisniewski, Jessica A; Rood, Julian I

    2017-05-01

    The Gram-positive pathogen Clostridium perfringens possesses a family of large conjugative plasmids that is typified by the tetracycline resistance plasmid pCW3. Since these plasmids may carry antibiotic resistance genes or genes encoding extracellular or sporulation-associated toxins, the conjugative transfer of these plasmids appears to be important for the epidemiology of C. perfringens-mediated diseases. Sequence analysis of members of this plasmid family identified a highly conserved 35kb region that encodes proteins with various functions, including plasmid replication and partitioning. The tcp conjugation locus also was identified in this region, initially based on low-level amino acid sequence identity to conjugation proteins from the integrative conjugative element Tn916. Genetic studies confirmed that the tcp locus is required for conjugative transfer and combined with biochemical and structural analyses have led to the development of a functional model of the Tcp conjugation apparatus. This review summarises our current understanding of the Tcp conjugation system, which is now one of the best-characterized conjugation systems in Gram-positive bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Chemistry of Oligonucleotibe-Gold Nanoparticle Conjugates

    National Research Council Canada - National Science Library

    Letsinger, Robert

    2003-01-01

    Conjugates prepared by immobilizing thiol-terminated oligonucleotides onto gold nanoparticles from stable colloidal solutions in aqueous media The oligo nucleotides can serve as linkers to organize...

  20. Modelling conjugation with stochastic differential equations

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo; Hasman, Henrik

    2010-01-01

    using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared......Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two...

  1. 147 ONE POT METHOD FOR THE SYNTHESIS OF ARYLIDENE ...

    African Journals Online (AJOL)

    The reactivity of condensing aldehyde is an important factor in the synthesis. Presence of alcohol enhances the formation of products. This fact have been utilized for alkali catalyzed synthesis of many arylidene flavanones been reported by them. The special feature of long conjugation with 4-keto group of flavanone moiety.

  2. Near-infrared (NIR) emitting conjugated polymers for biomedical applications (Presentation Recording)

    Science.gov (United States)

    Repenko, Tatjana; Kuehne, Alexander J. C.

    2015-10-01

    Fluorescent biomedical markers of today such as dye-infiltrated colloids, microgels and quantum dots suffer from fast bleaching, lack surface functionality (for targets or pharmaceutical agents) and potentially leach heavy metals in case of quantum dots (e.g. Cd). By contrast, conjugated polymer particles are non-cytotoxic, exhibit reduced bleaching, as the entire particle consists of fluorophore, they are hydrophobic and show high quantum yields. Consequently, conjugated polymer particles represent ideal materials for biological applications and imaging. However currently, conjugated polymer particles for biomedical imaging usually lack near-infrared (NIR) emission and are polydisperse. Fluorescent agents with emission in the NIR spectrum are interesting for biomedical applications due to their low photo-damage towards biological species and the ability of NIR radiation to penetrate deep into biological tissue.. I will present the development and synthesis of new conjugated polymers particles with fluorescence in the NIR spectral region for bio-imaging and clinical diagnosis. The particle synthesis proceeds in a one-step Pd or Ni-catalyzed dispersion polymerization of functional NIR emitters. The resulting monodisperse conjugated polymer particles are obtained as a dispersion in a non-hazardous solvent. Different sizes in the sub-micrometer range with a narrow size distribution can be produced. Furthermore biological recognition motifs can be easily attached to the conjugated polymers via thiol-yne click-chemistry providing specific tumor targeting without quenching of the fluorescence. References [1] Kuehne AJC, Gather MC, Sprakel J., Nature Commun. 2012, 3, 1088. [2] Repenko T, Fokong S, De Laporte L, Go D, Kiessling F, Lammers T, Kuehne AJC.,Chem Commun 2015, accepted.

  3. Removal of Uranium and Associated Contaminants from Aqueous Solutions Using Functional Carbon Nanotubes-Sodium Alginate Conjugates

    Directory of Open Access Journals (Sweden)

    Hussein Allaboun

    2016-02-01

    Full Text Available Synthesis of hydrophilic/hydrophobic beads from functional carbon nanotubes (CNTs conjugated with sodium alginate was investigated. Glutaraldehyde was used as a coupling agent and Ca2+ as a crosslinking agent. The formed conjugate comprises two-dimensional sheets of sodium alginate bounded to long tufts of functional CNT tails of micro-size geometry. Detailed characterization of the conjugates was performed using thermogravimetric analysis (TGA and its first derivative (DTG, Fourier transform infrared (FTIR, and scanning electron microscope (SEM techniques. Different ratios of the conjugate were successfully prepared and used as biodegradable environmentally friendly sorbents. Removal of U6+, V3+, Cr3+, Mo3+, Pb2+, Mn2+, Cu2+, Ti4+ and Ni2+ from aqueous solutions using the synthesized biosorbent was experimentally demonstrated. Maximum metal uptake of 53 mg/g was achieved using the % Functional CNTs = 33 sample.

  4. Versatile phosphoramidation reactions for nucleic acid conjugations with peptides, proteins, chromophores, and biotin derivatives.

    Science.gov (United States)

    Wang, Tzu-Pin; Chiou, Yi-Jang; Chen, Yi; Wang, Eng-Chi; Hwang, Long-Chih; Chen, Bing-Hung; Chen, Yen-Hsu; Ko, Chun-Han

    2010-09-15

    Chemical conjugations of nucleic acids with macromolecules or small molecules are common approaches to study nucleic acids in chemistry and biology and to exploit nucleic acids for medical applications. The conjugation of nucleic acids such as oligonucleotides with peptides is especially useful to circumvent cell delivery and specificity problems of oligonucleotides as therapeutic agents. However, current approaches are limited and inefficient in their ability to afford peptide-oligonucleotide conjugates (POCs). Here, we report an effective and reproducible approach to prepare POCs and other nucleic acid conjugates based on a newly developed nucleic acid phosphoramidation method. The development of a new nucleic acid phosphoramidation reaction was achieved by our successful synthesis of a novel amine-containing biotin derivative used to systematically optimize the reactions. The improved phosphoramidation reactions dramatically increased yields of nucleic acid-biotin conjugates up to 80% after 3 h reaction. Any nucleic acids with a terminal phosphate group are suitable reactants in phosphoramidation reactions to conjugate with amine-containing molecules such as biotin and fluorescein derivatives, proteins, and, most importantly, peptides to enable the synthesis of POCs for therapeutic applications. Polymerase chain reactions (PCRs) to study incorporation of biotin or fluorescein-tagged DNA primers into the reaction products demonstrated that appropriate controls of nucleic acid phosphoramidation reactions incur minimum adverse effects on inherited base-pairing characteristics of nucleotides in nucleic acids. The phosphoramidation approach preserves the integrity of hybridization specificity in nucleic acids when preparing POCs. By retaining integrity of the nucleic acids, their effectiveness as therapeutic reagents for gene silencing, gene therapy, and RNA interference is ensured. The potential for POC use was demonstrated by two-step phosphoramidation reactions to

  5. Subgap Absorption in Conjugated Polymers

    Science.gov (United States)

    Sinclair, M.; Seager, C. H.; McBranch, D.; Heeger, A. J; Baker, G. L.

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination.

  6. Analysis of anabolic androgenic steroids as sulfate conjugates using high performance liquid chromatography coupled to tandem mass spectrometry.

    Science.gov (United States)

    Rzeppa, S; Heinrich, G; Hemmersbach, P

    2015-01-01

    Improvements in doping analysis can be effected by speeding up analysis time and extending the detection time. Therefore, direct detection of phase II conjugates of doping agents, especially anabolic androgenic steroids (AAS), is proposed. Besides direct detection of conjugates with glucuronic acid, the analysis of sulfate conjugates, which are usually not part of the routine doping control analysis, can be of high interest. Sulfate conjugates of methandienone and methyltestosterone metabolites have already been identified as long-term metabolites. This study presents the synthesis of sulfate conjugates of six commonly used AAS and their metabolites: trenbolone, nandrolone, boldenone, methenolone, mesterolone, and drostanolone. In the following these sulfate conjugates were used for development of a fast and easy analysis method based on sample preparation using solid phase extraction with a mixed-mode sorbent and detection by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Validation demonstrated the suitability of the method with regard to the criteria given by the technical documents of the World Anti-Doping Agency (WADA). In addition, suitability has been proven by successful detection of the synthesized sulfate conjugates in excretion urines and routine doping control samples. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Size-Dependent Photodynamic Activity of Gold Nanoparticles Conjugate of Water Soluble Purpurin-18-N-Methyl-D-Glucamine

    Directory of Open Access Journals (Sweden)

    Byambajav Lkhagvadulam

    2013-01-01

    Full Text Available Gold nanoparticles (GNPs conjugates of water soluble ionic photosensitizer (PS, purpurin-18-N-methyl-D-glucamine (Pu-18-NMGA, were synthesized using various molar ratios between HAuCl4 and Pu-18-NMGA without adding any particular reducing agents and surfactants. The PS-GNPs conjugates showed long wavelength absorption of range 702–762 nm, and their different shapes and diameters depend on the molar ratios used in the synthesis. In vitro anticancer efficacy of the PS-GNPs conjugates was investigated by MTT assay against A549 cells, resulting in higher photodynamic activity than that of the free Pu-18-NMGA. Among the PS-GNPs conjugates, the GNPs conjugate from the molar ratio of 1 : 2 (Au(III: Pu-18-NMGA exhibits the highest photodynamic activity corresponding to bigger size (~60 nm of the GNPs conjugate which could efficiently transport the PS into the cells than that of smaller size of the GNPs conjugate.

  8. Non-covalent conjugates of single-walled carbon nanotubes and folic acid for interaction with cells overexpressing folate receptors

    DEFF Research Database (Denmark)

    Castillo, John J.; Rindzevicius, Tomas; Novoa, Leidy V.

    2013-01-01

    We here present amethod to form a noncovalent conjugate of single-walled carbon nanotubes and folic acid aimed to interact with cells over-expressing folate receptors. The bonding was obtained without covalent chemical functionalization using a simple, rapid “one pot” synthesis method. The zeta p...

  9. Unsymmetrical triphenylamine-oligothiophene hybrid conjugated systems as donor materials for high-voltage solution-processed organic solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Ripaud, Emilie; Rousseau, Theodulf; Leriche, Philippe; Roncali, Jean [Group Linear Conjugated Systems, CNRS Moltech-Anjou, University of Angers, 2Bd Lavoisier, 49045 Angers (France)

    2011-07-15

    The synthesis of unsymmetrical triphenylamine-oligothiophene hybrid conjugated systems bearing dicyanovinyl electron acceptor end-groups is presented. When used as molecular donor materials in solution-processed bulk heteroj-unction solar cells, these compounds lead to efficient devices with very high open-circuit voltages. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  10. Double Conjugate Addition of Dithiols to Propargylic Carbonyl Systems To Generate Protected 1,3-Dicarbonyl Compounds

    NARCIS (Netherlands)

    Sneddon, Helen F.; Heuvel, Alexandra van den; Hirsch, Anna K.H.; Booth, Richard A.; Shaw, David M.; Gaunt, Matthew J.; Ley, Steven V.

    2006-01-01

    The work describes the efficient double conjugate addition of ethane and propane dithiols in the presence of sodium methoxide to a wide variety of propargylic carbonyl containing compounds. The products of these reactions are differentiated, 1,3-dicarbonyl systems useful for various synthesis

  11. System Development from Organic Solvents to Ionic Liquids for Synthesiz-ing Ascorbyl Esters with Conjugated Linoleic Acids

    DEFF Research Database (Denmark)

    Yang, Zhiyong; Schultz, Lise; Guo, Zheng

    2012-01-01

    The aim of this paper is to screen suitable reaction systems for the modification of antioxidants through enzy-matic synthesis. Enzymatic esterification of ascorbic acid with conjugated linoleic acid (CLA) was investigated as a mod-el. Four organic solvents and five different enzymes were evaluat...

  12. Conjugated estrogens and breast cancer risk.

    Science.gov (United States)

    Campagnoli, C; Ambroggio, S; Biglia, N; Sismondi, P

    1999-12-01

    Available epidemiologic data suggest the possibility that the use of oral conjugated equine estrogens (CEE) 0.625 mg/day as a first-choice dose could be associated with a very limited (if any) breast cancer risk increase. Some biological peculiarities of oral CEE back the possibility of a limited detrimental effect on breast tissue, due to either direct or indirect actions. Direct actions. Some experimental findings suggest that the 17 alpha-dihydroderivatives of equilenin and equilin (15% of the CEE components) have a non-estrogenic or even an anti-estrogenic effect on breast tissue. This could partially counterbalance the stimulatory action of the other CEE components. Indirect actions. Oral estrogens, through their metabolic and hepatocellular effects (emphasized by the first liver passage) cause a sharp increase in sex hormone binding globulin (SHBG) level which is followed by a lower quantity of both estrogen and androgen in the free, bioavailable, form. More importantly, they cause a decrease in circulating insulin-like growth factor I (IGF-I) activity, due to both a reduction in IGF-I synthesis by the liver and an increase in IGF-binding protein-1 level. A strong relationship between breast cancer risk and the concentration of circulating IGF-I in premenopausal women has been recently found. Actually, estrogens and IGF-I have a synergistic effect on cell proliferation, and IGF-I is necessary for maximum estrogen-receptor activation in breast cancer cell lines. The possibility does exist that the SHBG level increase and the IGF-I bioavailability decrease, caused by oral CEE, balance the increased estrogen stimulation on breast tissue.

  13. Optimization of the conjugation method for a serogroup B/C meningococcal vaccine.

    Science.gov (United States)

    Fukasawa, Lucila O; Schenkman, Rocilda P F; Perciani, Catia T; Carneiro, Sylvia M; Dias, Waldely O; Tanizaki, Martha M

    2006-11-01

    A conjugate meningococcal vaccine against serogroup B/C consisting of capsular PS (polysaccharide) from serogroup C conjugated to OMV (outer membrane vesicle) from serogroup B would be a very useful vaccine in regions where there is a prevalence of both serogroups, for example in Brazil. For this purpose, the conjugation method that uses ADHy (adipic acid dihydrazide) as spacer and a carbodi-imide derivative, EDAC [1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide], as catalyser was optimized looking for synthesis yield and maintenance of the antigenicity of both components. The best synthesis conditions preserving the vaccine immunogenicity resulted in a final yield of approx. 17%. Immunogenicity of the vaccine was highest when 10% of the sialic acid residues of the PS were occupied by the ADHy spacer. Sterilization of the conjugate by filtration through a 0.22-microm-pore-size membrane resulted in a low recovery of protein and PS (approximately 50%), although the vaccine immunogenicity was maintained. Using gamma irradiation on freeze-dried sample, it was possible to maintain the integrity of OMV structure and, consequently, its ability to induce bactericidal antibodies.

  14. Folate-conjugated gold nanoparticle as a new nanoplatform for targeted cancer therapy.

    Science.gov (United States)

    Samadian, Hadi; Hosseini-Nami, Samira; Kamrava, Seyed Kamran; Ghaznavi, Habib; Shakeri-Zadeh, Ali

    2016-11-01

    Conventional cancer treatment methods suffer from many limitations such as non-specificity and low efficacy in discrimination between healthy and cancer cells. Recent developments in nanotechnology have introduced novel and smart therapeutic nanomaterials that basically take advantage of various targeting approaches. Targeted nanomaterials selectively bind to the cancer cells and affect them with minor effects on healthy cells. Folic acid (folate) is an essential molecule in DNA synthesis pathway which is highly needed for cancer cell duplication. Some certain cancer cells overexpress folate receptors higher than normal cells, and this fact is the basis of folate targeting strategy. There are many publications reporting various folate conjugated nanomaterials among which folate-conjugated gold nanoparticles hold great promises in targeted cancer therapy. Gold nanoparticles have been identified as promising candidates for new cancer therapy modalities because of biocompatibility, easy synthesis and functionalization, chemo-physical stability, and optical tunable characteristics. In the last decade, there has been a significant explosion in gold nanoparticles research, with a rapid increase in publications related to the area of biomedicine. Although there are many reports published on "gold nanoparticles" and "folate targeting," there are a few reports on "folate-conjugated gold nanoparticles" in biomedical literature. This paper intends to review and illustrate the recent advances in biomedicine which have been designed on the basis of folate-conjugated gold nanoparticles.

  15. Designing dapsone polymer conjugates for controlled drug delivery.

    Science.gov (United States)

    Rojo, Luis; Fernandez-Gutierrez, Mar; Deb, Sanjukta; Stevens, Molly M; San Roman, Julio

    2015-11-01

    Polymer-drug conjugates have significantly influenced polymer therapeutics over the last decade via controlled pharmacokinetics. Dapsone (4,4'-diamino diphenylsulphone) is not only widely used in the treatment of leprosy but forms an essential component in the treatment of autoimmune inflammatory diseases and malaria. However, its low bioavailability and non-specific distribution in the body leads to absorption throughout organs including skin, liver, and kidneys that can cause serious side effects. Thus, in this study we report the synthesis of polymer-drug conjugates of dapsone covalently bonded to macromolecular chains towards the development of new bioactive polymeric formulations with anti-inflammatory properties. Dapsone was functionalised with an acrylic moiety in which the acrylamide residue was directly bonded to one of the aromatic rings of dapsone. This functionalisation yielded an unsymmetrical dapsone methacrylamide (DapMA) structure, which on free radical polymerisation and co-polymerisation with HEMA yielded polymers of hydrocarbon macromolecules with pendant dapsone units. Thermal and size-exclusion chromatographic analysis revealed an increase in thermal stabilisation of the homopolymer (p(DapMA)) in comparison to the copolymer (p(Dap-co-HEMA)) with relatively high average molecular weight. The polymer conjugates exhibited high stability with low dapsone release from the polymeric backbone due to hydrolysis. However, a significant anti-inflammatory activity in a nitric oxide inhibition assay confirmed that this property was the consequence of only the macromolecular composition and not related to the release of low molecular weight compounds. Thus, the conjugation of dapsone to macromolecular systems provides a synthetic route to incorporate this drug into polymeric systems, facilitating their development into new anti-inflammatory therapies. The dapsone-conjugated methacrylic monomer and polymer derivatives with anti-inflammatory properties

  16. DENDRIMER CONJUGATES FOR SELECTIVE OF PROTEIN AGGREGATES

    DEFF Research Database (Denmark)

    2004-01-01

    Dendrimer conjugates are presented, which are formed between a dendrimer and a protein solubilising substance. Such dendrimer conjugates are effective in the treatment of protein aggregate-related diseases (e.g. prion-related diseases). The protein solubilising substance and the dendrimer together...

  17. Catalytic enantioselective conjugate addition with Grignard reagents

    NARCIS (Netherlands)

    Lopez, Fernando; Minnaard, Adriaan J.; Feringa, Ben L.

    In this Account, recent advances in catalytic asymmetric conjugate addition of Grignard reagents are discussed. Synthetic methodology to perform highly enantioselective Cu-catalyzed conjugate addition of Grignard reagents to cyclic enones with ee's up to 96% was reported in 2004 from our

  18. Tales of conjugation and sex pheromones

    Science.gov (United States)

    2011-01-01

    This review covers highlights of the author's experience becoming and working as a plasmid biologist. The account chronicles a progression from studies of ColE1 DNA in Escherichia coli to Gram-positive bacteria with an emphasis on conjugation in enterococci. It deals with gene amplification, conjugative transposons and sex pheromones in the context of bacterial antibiotic resistance. PMID:22016844

  19. Preconditioning the modified conjugate gradient method ...

    African Journals Online (AJOL)

    In this paper, the convergence analysis of the conventional conjugate Gradient method was reviewed. And the convergence analysis of the modified conjugate Gradient method was analysed with our extension on preconditioning the algorithm. Convergence of the algorithm is a function of the condition number of M-1A.

  20. Singularities and Conjugate Points in FLRW Spacetimes

    NARCIS (Netherlands)

    Lam, Huibert het; Prokopec, Tom

    2017-01-01

    Conjugate points play an important role in the proofs of the singularity theorems of Hawking and Penrose. We examine the relation between singularities and conjugate points in FLRW spacetimes with a singularity. In particular we prove a theorem that when a non-comoving, non-spacelike geodesic in a

  1. The Conjugate Acid-Base Chart.

    Science.gov (United States)

    Treptow, Richard S.

    1986-01-01

    Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

  2. Star Polymer-Drug Conjugates with pH-Controlled Drug Release and Carrier Degradation

    Directory of Open Access Journals (Sweden)

    H. Kostková

    2017-01-01

    Full Text Available In this study, we describe the design, synthesis, and physicochemical and preliminary biological characteristics of new biodegradable, high-molecular-weight (HMW drug delivery systems with star-like architectures bearing the cytotoxic drug doxorubicin (DOX attached by a hydrazone bond-containing spacer. The star polymers were synthesized by grafting semitelechelic N-(2-hydroxypropyl methacrylamide (HPMA copolymers on a 2,2-bis(hydroxymethylpropionic acid- (bis-MPA- based polyester dendritic core. The molecular weight of the star polymers ranged from 280 to 450 000 g/mol and could be adjusted by proper selection of the bis-MPA dendrimer generation and by considering the polymer to dendrimer molar ratio. The biodegradation of the polymer conjugates is based on the spontaneous slow hydrolysis of the dendritic core in neutral physiological conditions. Hydrazone spacers in the conjugates were fairly stable at neutral pH (7.4 mimicking blood stream conditions, and DOX was released from the conjugates under mild acidic conditions simulating the tumor cell microenvironment in endosomes and lysosomes (pH 5. Finally, we have shown the significant in vitro cytotoxicity of the star polymer-DOX conjugate on selected cancer cell lines with IC50 values almost comparable with that of the free drug and higher than that observed for a linear polymer-DOX conjugate with much lower molecular weight.

  3. Surface conjugation of poly (dimethyl siloxane) with itaconic acid-based materials for antibacterial effects

    Science.gov (United States)

    Birajdar, Mallinath S.; Cho, Hyunjoo; Seo, Youngmin; Choi, Jonghoon; Park, Hansoo

    2018-04-01

    Poly (dimethyl siloxane) (PDMS) is widely used in various biomedical applications. However, the PDMS surface is known to cause bacterial adhesion and protein absorption issues due to its high hydrophobicity. Therefore, the development of antibacterial and anti-protein products is necessary to prevent these problems. In this study, to improve its antibacterial property and prevent protein adsorption, PDMS surfaces were conjugated with itaconic acid (IA) and poly (itaconic acid) (PIA) via a chemical method. Additionally, IA and PIA were physically blended with PDMS to compare the antibacterial properties of these materials with those of the chemically conjugated PDMS surfaces. The successful synthesis of the PIA polymer structure was confirmed by proton nuclear magnetic resonance (1H NMR) spectroscopy. The successful conjugation of IA and PIA on PDMS was confirmed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), water contact angle measurements, and microbicinchoninic acid (BCA) protein assay analyses. The PDMS surfaces functionalized with IA and PIA by the conjugation method better prevented protein adsorption than the bare PDMS. Therefore, these surface-conjugated PDMS can be used in various biomedical applications.

  4. Molecular and biochemical analysis of conjugation and adolescence in Tetrahymena thermophila

    International Nuclear Information System (INIS)

    Rogers, M.B.

    1986-01-01

    A previously unrecognized stage in the development of sexual maturity in Tetrahymena thermophila, adolescence, has been described. When the progeny of successfully mated cells are grown logarithmically, they are unable to form mating pairs for about 65 generations. This period is known as immaturity. During the next stage, adolescence, the progeny pair with mature cells but not with other adolescent cells despite the presence of complementary mating types. Adolescence persists for 20-25 generations before the cells attain maturity (the ability to mate with any cell of different mating type). Once paired with mature cells, adolescents successfully complete conjugation was shown genetically. Mating pairs formed between adolescent and mature cells are indistinguishable from those formed between mature cells by the criteria of cytology and two-dimensional gel electrophoresis of proteins extracted from mating pairs pulse-labelled with [ 35 S]methionine. An analysis of proteins induced during the first ten hours of conjugation was carried out using two-dimensional gel electrophoresis. The protein patterns obtained from all controls were similar. The synthesis of numerous large and basic proteins were induced during conjugation. The majority of the proteins were detected during meiosis and none were mating type specific. A library of micronuclear DNA was constructed in the plasmic PUC18. The library was screened by differential colony hybridization using cDNA complementary to polyA + RNA isolated from conjugating and control cells. Eight recombinant clones were isolated which contain sequences transcriptionally induced in conjugating cells

  5. Approximate error conjugation gradient minimization methods

    Science.gov (United States)

    Kallman, Jeffrey S

    2013-05-21

    In one embodiment, a method includes selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, calculating an approximate error using the subset of rays, and calculating a minimum in a conjugate gradient direction based on the approximate error. In another embodiment, a system includes a processor for executing logic, logic for selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, logic for calculating an approximate error using the subset of rays, and logic for calculating a minimum in a conjugate gradient direction based on the approximate error. In other embodiments, computer program products, methods, and systems are described capable of using approximate error in constrained conjugate gradient minimization problems.

  6. Study of conjugation and radiolabeling of monoclonal antibody rituximab for use in radionuclide therapy

    International Nuclear Information System (INIS)

    Massicano, Adriana Vidal Fernandes

    2011-01-01

    stability in human serum did not suggest high metabolic degradation by serum enzymes. The labeled conjugate showed high serum protein binding, suggesting slow blood clearance, which was confirmed by in vivo studies. The labeled conjugate presented high uptake in the liver, in accordance to biodistribution pattern of monoclonal antibodies. The preliminary competitive binding studies indicated a specific binding and suggest that the synthesis of 177 Lu-DOTA-rituximab did not compromise its binding to CD20 positive tumor cells. (author)

  7. Molecular design toward highly efficient photovoltaic polymers based on two-dimensional conjugated benzodithiophene.

    Science.gov (United States)

    Ye, Long; Zhang, Shaoqing; Huo, Lijun; Zhang, Maojie; Hou, Jianhui

    2014-05-20

    As researchers continue to develop new organic materials for solar cells, benzo[1,2-b:4,5-b']dithiophene (BDT)-based polymers have come to the fore. To improve the photovoltaic properties of BDT-based polymers, researchers have developed and applied various strategies leading to the successful molecular design of highly efficient photovoltaic polymers. Novel polymer materials composed of two-dimensional conjugated BDT (2D-conjugated BDT) have boosted the power conversion efficiency of polymer solar cells (PSCs) to levels that exceed 9%. In this Account, we summarize recent progress related to the design and synthesis of 2D-conjugated BDT-based polymers and discuss their applications in highly efficient photovoltaic devices. We introduce the basic considerations for the construction of 2D-conjugated BDT-based polymers and systematic molecular design guidelines. For example, simply modifying an alkoxyl-substituted BDT to form an alkylthienyl-substituted BDT can improve the polymer hole mobilities substantially with little effect on their molecular energy level. Secondly, the addition of a variety of chemical moieties to the polymer can produce a 2D-conjugated BDT unit with more functions. For example, the introduction of a conjugated side chain with electron deficient groups (such as para-alkyl-phenyl, meta-alkoxyl-phenyl, and 2-alkyl-3-fluoro-thienyl) allowed us to modulate the molecular energy levels of 2D-conjugated BDT-based polymers. Through the rational design of BDT analogues such as dithienobenzodithiophene (DTBDT) or the insertion of larger π bridges, we can tune the backbone conformations of these polymers and modulate their photovoltaic properties. We also discuss the influence of 2D-conjugated BDT on polymer morphology and the blends of these polymers with phenyl-C61 (or C71)-butyric acid methyl ester (PCBM). Finally, we summarize the various applications of the 2D-conjugated BDT-based polymers in highly efficient PSC devices. Overall, this Account

  8. Trilobolide-porphyrin conjugates: On synthesis and biological effects evaluation

    Czech Academy of Sciences Publication Activity Database

    Tomanová, P.; Rimpelová, S.; Jurášek, M.; Buděšínský, Miloš; Vejvodová, L.; Ruml, T.; Kmoníčková, E.; Drašar, P. B.

    2015-01-01

    Roč. 97, SI (2015), s. 8-12 ISSN 0039-128X Grant - others:GA ČR(CZ) GA14-04329S; GA MŠk(CZ) ED2.1.00/03.0076 Institutional support: RVO:61388963 Keywords : trilobolide * porphyrin * nitric oxide * fluorescence microscopy Subject RIV: CE - Biochemistry Impact factor: 2.513, year: 2015

  9. Synthesis and characterization of polyamidoamine conjugates of neridronic acid

    CSIR Research Space (South Africa)

    Aderibigbe, BA

    2015-10-01

    Full Text Available transform spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM) and energy-dispersive X-ray analysis (EDX). NMR, TGA, XRD and FTIR confirmed the successful incorporation of the bisphosphonate on to the carriers. The mass percentage...

  10. Pyrene appended bile acid conjugates: Synthesis and a structure ...

    Indian Academy of Sciences (India)

    us to connect the existing gelator motifs into hybrid structures and study their gelation properties in solu- tion. We envisioned that by adding a pyrene moiety ...... seen with the simplest pyrene molecule 1-pyrene car- boxylic acid (19) or its mixture with 1-aminopyrene. (20) (prepared by heating the 1:1 mixture of the amine.

  11. Pyrene appended bile acid conjugates: Synthesis and a structure ...

    Indian Academy of Sciences (India)

    mmol) drop-wise for 5 minutes. The resulting mixture was stirred for addi- tional 12h. The DCU formed were filtered and the filtrate was diluted with 10mL of DCM. The DCM layer was washed with sat. NaHCO3 (2 × 5mL) and water (2×5mL).

  12. Synthesis of Conjugated Polymers via Polymer Elimination Reactions.

    Science.gov (United States)

    1987-04-16

    03)2S and HCI from poly(p- xylene -a-dimethyl- sulfonium chloride), a soluble polyelectrolyte (see Figure 3). Highly oriented Durham PA and PPV films...electronic spectrum of the pristine precursor polymer fil. was obtained and then bromide vapor was introducel into the reaction vessel. In situ FTIR spectra in...current converter. The cyclic voltammogras were recorded on a HP Model 7040A X-Y recorder. Results Figure 7 shows the FTIR spectra of initial precursor

  13. New Conjugated Benzothiazole-N-oxides: Synthesis and Biological Activity

    Directory of Open Access Journals (Sweden)

    Pavlína Foltínová

    2009-12-01

    Full Text Available Eleven new 2-styrylbenzothiazole-N-oxides have been prepared by aldol – type condensation reactions between 2-methylbenzothiazole–N-oxide and para-substituted benzaldehydes. Compounds with cyclic amino substituents showed typical push-pull molecule properties. Four compounds were tested against various bacterial strains as well as the protozoan Euglena gracilis as model microorganisms. Unlike previously prepared analogous benzothiazolium salts, only weak activity was recorded.

  14. Expeditious synthesis of coumarin-pyridone conjugates molecules ...

    Indian Academy of Sciences (India)

    RAJNI KHAJURIA

    Escherichia coli (MTC 119), ... diluting the solution in the 100 μL volume of aforementioned media in a 96-well U bottom micro titre plate. Popular ... ther diluted and added in 100 μL volume at final inoculums of 1 × 105 CFU/mL. For fungal cultures, 1 ...

  15. Synthesis of conjugated polymers with complex architecture for photovoltaic applications

    DEFF Research Database (Denmark)

    Kiriy, Anton; Krebs, Frederik C

    2017-01-01

    A common approach to bulk heterojunction solar cells involves a “trialand- error” approach in finding optimal kinetically unstable morphologies. An alternative approach assumes the utilization of complex polymer architectures, such as donor–acceptor block copolymers. Because of a covalent...

  16. The Synthesis of Substituted Piperazine-cholesterol Conjugates for ...

    African Journals Online (AJOL)

    NICO

    piperazines by way of a carbamate linker. An advantage of the strategy utilized was that it afforded the desired compounds in high yields. Moreover, the approach allowed for incorporation of functional diversity on the piperazine head group because of the significant variety of commercially available substituted piperazines.

  17. Synthesis of streptavidin-conjugated magnetic nanoparticles for DNA detection

    Energy Technology Data Exchange (ETDEWEB)

    Gong Peijun, E-mail: skygpj@zjnu.cn; Peng Zheyang; Wang Yao; Qiao Ru; Mao Weixing; Qian Haisheng; Zhang Mengya; Li Congcong; Shi Shenyuan [College of Chemistry and Life Sciences, Zhejiang Normal University (China)

    2013-04-15

    In this paper, we report a fabrication of streptavidin-coated magnetic nanoparticles used for DNA detection. Initially, amino-functionalized Fe{sub 3}O{sub 4} nanoparticles with high saturation magnetization are prepared by a photopolymerization method using allylamine as monomer. It is followed by covalent immobilization of streptavidin onto the particle surface via a two-step reaction using glutaraldehyde as coupling agent. Streptavidin-coated magnetic nanoparticles are characterized and further tested for their ability to capture DNA target after binding biotinylated oligonucleotide probes. The results show that the products ({approx}27.2 nm) have a maximum biotin-binding capacity of 0.71 nmol mg{sup -1} when the immobilization reaction is conducted with a mass ratio of streptavidin to magnetic carriers above 0.2 in phosphate buffered saline (pH 7.4) for 24 h. In addition, highly negative {zeta}-potential and good magnetic susceptibility of the nanocomposites make them applicable for DNA collection and detection, which is verified by the results from the preliminary application of streptavidin-coated magnetic nanoparticles in DNA detection. Therefore, the magnetic nanoparticles provide a promising approach for rapid collection and detection of gene.

  18. Synthesis of streptavidin-conjugated magnetic nanoparticles for DNA detection

    Science.gov (United States)

    Gong, Peijun; Peng, Zheyang; Wang, Yao; Qiao, Ru; Mao, Weixing; Qian, Haisheng; Zhang, Mengya; Li, Congcong; Shi, Shenyuan

    2013-04-01

    In this paper, we report a fabrication of streptavidin-coated magnetic nanoparticles used for DNA detection. Initially, amino-functionalized Fe3O4 nanoparticles with high saturation magnetization are prepared by a photopolymerization method using allylamine as monomer. It is followed by covalent immobilization of streptavidin onto the particle surface via a two-step reaction using glutaraldehyde as coupling agent. Streptavidin-coated magnetic nanoparticles are characterized and further tested for their ability to capture DNA target after binding biotinylated oligonucleotide probes. The results show that the products ( 27.2 nm) have a maximum biotin-binding capacity of 0.71 nmol mg-1 when the immobilization reaction is conducted with a mass ratio of streptavidin to magnetic carriers above 0.2 in phosphate buffered saline (pH 7.4) for 24 h. In addition, highly negative ζ-potential and good magnetic susceptibility of the nanocomposites make them applicable for DNA collection and detection, which is verified by the results from the preliminary application of streptavidin-coated magnetic nanoparticles in DNA detection. Therefore, the magnetic nanoparticles provide a promising approach for rapid collection and detection of gene.

  19. Pyrene appended bile acid conjugates: Synthesis and a structure ...

    Indian Academy of Sciences (India)

    DCA) turned out to be effective in the gel formation with many organic solvents although the gelation has to be triggered by the addition of a charge transfer (CT) agent 2,4,7-trinitrofluorenone (TNF). The special feature of these molecules is that ...

  20. Expeditious synthesis of coumarin-pyridone conjugates molecules ...

    Indian Academy of Sciences (India)

    Department of Chemistry, University of Jammu, Jammu, Jammu and Kashmir 180 006, India; Department of Chemistry and Chemical Sciences, Central University of Jammu, Jammu, Jammu and Kashmir, India; Department of Chemistry, Government Degree College, Kathua, Jammu and Kashmir 184 101, India ...

  1. Synthesis of sugars catalysed by microgel conjugated rabbit muscle ...

    African Journals Online (AJOL)

    natural aldehyde acceptors under similar conditions. Reaction was fastest in 1:3 DMSO/ H2O, faster than in aqueous medium the environment in which this enzyme normally operates. Preparation of a non-natural sugar using this system is related.

  2. TAT peptide and its conjugates: proteolytic stability.

    Science.gov (United States)

    Grunwald, Jacob; Rejtar, Tomas; Sawant, Rupa; Wang, Zhouxi; Torchilin, Vladimir P

    2009-08-19

    The proteolytic cleavage of TATp, TATp-PEG(1000)-PE conjugate (TATp-conjugate), and TATp as TATp-conjugate in mixed micelles made of TATp-conjugate and PEG(5000)-PE (2.5% mol of TATp-conjugate, TATp-Mic) were studied by HPLC with fluorescent detection using fluorenylmethyl chloroformate (FMOC) labeling and by MALDI-TOF MS analysis. The cleavage kinetics were analyzed in human blood plasma and in trypsin-containing phosphate buffered saline (PBS), pH 7.4, to simulate the proteolytic activity of human plasma. The trypsinolysis of free TATp, TATp-conjugate, and TATp-Mic revealed that the main initial fragmentation is an endocleavage at the carboxyl terminus resulting in an Arg-Arg (RR) dimer. The trypsinolysis followed pseudo-first-order kinetics. The cleavage of the free TATp was relatively fast with a half-life of a few minutes (t(1/2) ∼ 3.5 min). The TATp-conjugate showed more stability with about a 3-fold increase in half-life (t(1/2) ∼ 10 min). TATp in TATp-Mic was highly protected against proteolysis with an over 100-fold increase in half-life (t(1/2) ∼ 430 min). The shielding of TATp by PEG moieties in the proposed TATp-Mic is of great importance for its potential use as a cell-penetrating moiety for multifunctional "smart" drug delivery systems with detachable PEG.

  3. Sequence-specific DNA alkylation targeting for Kras codon 13 mutation by pyrrole-imidazole polyamide seco-CBI conjugates.

    Science.gov (United States)

    Taylor, Rhys Dylan; Asamitsu, Sefan; Takenaka, Tomohiro; Yamamoto, Makoto; Hashiya, Kaori; Kawamoto, Yusuke; Bando, Toshikazu; Nagase, Hiroki; Sugiyama, Hiroshi

    2014-01-27

    Hairpin N-methylpyrrole-N-methylimidazole polyamide seco-CBI conjugates 2-6 were designed for synthesis by Fmoc solid-phase synthesis, and their DNA-alkylating activities against the Kras codon 13 mutation were compared by high-resolution denaturing gel electrophoresis with 225 base pair (bp) DNA fragments. Conjugate 5 had high reactivity towards the Kras codon 13 mutation site, with alkylation occurring at the A of the sequence 5'-ACGTCACCA-3' (site 2), including minor 1 bp-mismatch alkylation against wild type 5'-ACGCCACCA-3' (site 3). Conjugate 6, which differs from conjugate 5 by exchanging one Py unit with a β unit, showed high selectivity but only weakly alkylated the A of 5'-ACGTCACCA-3' (site 2). The hairpin polyamide seco-CBI conjugate 5 thus alkylates according to Dervan's pairing rule with the pairing recognition which β/β pair targets T-A and A-T pairs. SPR and a computer-minimized model suggest that 5 binds to the target sequence with high affinity in a hairpin conformation, allowing for efficient DNA alkylation. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Conjugated Polymers and Oligomers: Structural and Soft Matter Aspects

    DEFF Research Database (Denmark)

    conjugated polymer backbone, water soluble conjugated polyelectrolytes and surfactants, conjugated molecules and biomolecules and DNA and the advanced use of synchrotron radiation and electron microscopy to find out structural details in conjugated molecule films and devices as well as under ambient...

  5. Preliminary studies towards the preparation of reactive 3-pyrrolin-2-ones in conjugate addition reactions for the syntheses of potentially bioactive 2-pyrrolidinones and pyrrolidines

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Jose C.F. [Universidade Federal Fluminense, (UFF) Niteroi, RJ (Brazil). Inst. de Quimica]. E-mail: alvesjcf@yahoo.com.br

    2007-07-01

    Pyrrolin-2-ones and 2-pyrrolidinones are moieties often found in the structure of several biologically active natural products and 3-pyrrolin-2-ones are valuable starting materials in organic synthesis due to their ability to react as acceptors in conjugate addition reactions. In this article we report the initial results about the performed study aiming at the syntheses of reactive 3-pyrrolin-2-ones in conjugate addition reactions and the preparation of a potential precursor for the synthesis of the nootropic (+/-)-nebracetam. (author)

  6. Functional Hybrid Biomaterials based on Peptide-Polymer Conjugates for Nanomedicine

    Science.gov (United States)

    Shu, Jessica Yo

    The focus of this dissertation is the design, synthesis and characterization of hybrid functional biomaterials based on peptide-polymer conjugates for nanomedicine. Generating synthetic materials with properties comparable to or superior than those found in nature has been a "holy grail" for the materials community. Man-made materials are still rather simplistic when compared to the chemical and structural complexity of a cell. Peptide-polymer conjugates have the potential to combine the advantages of the biological and synthetic worlds---that is they can combine the precise chemical structure and diverse functionality of biomolecules with the stability and processibility of synthetic polymers. As a new family of soft matter, they may lead to materials with novel properties that have yet to be realized with either of the components alone. In order for peptide-polymer conjugates to reach their full potential as useful materials, the structure and function of the peptide should be maintained upon polymer conjugation. The success in achieving desirable, functional assemblies relies on fundamentally understanding the interactions between each building block and delicately balancing and manipulating these interactions to achieve targeted assemblies without interfering with designed structures and functionalities. Such fundamental studies of peptide-polymer interactions were investigated as the nature of the polymer (hydrophilic vs. hydrophobic) and the site of its conjugation (end-conjugation vs. side-conjugation) were varied. The fundamental knowledge gained was then applied to the design of amphiphiles that self-assemble to form stable functional micelles. The micelles exhibited exceptional monodispersity and long-term stability, which is atypical of self-assembled systems. Thus such micelles based on amphiphilic peptide-polymer conjugates may meet many current demands in nanomedicine, in particular for drug delivery of hydrophobic anti-cancer therapeutics. Lastly

  7. Stochastic differential equations used to model conjugation

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo

    be split into measurement noise and system noise. The system noise is used to compensate for those biological processes not explicitly described by the model. Many authors model conjugation by a simple mass action model first proposed by Levin et al. (1979). Also Michaelis-Menten dependence...... by an experiment conducted with E. faecium. In addition, we suggest that a 3rd order time-delay must be included in the model to account for the delay before a newly conjugated plasmid is expressed. A ML estimate of the parameters based on experimental data is found using the software CTSM. The conjugation rate......Stochastic differential equations (SDEs) are used to model horizontal transfer of antibiotic resis- tance by conjugation. The model describes the concentration of donor, recipient, transconjugants and substrate. The strength of the SDE model over the traditional ODE models is that the noise can...

  8. Deciphering conjugative plasmid permissiveness in wastewater microbiomes

    DEFF Research Database (Denmark)

    Jacquiod, Samuel Jehan Auguste; Brejnrod, Asker Daniel; Milani, Stefan Morberg

    2017-01-01

    Wastewater treatment plants (WWTPs) are designed to robustly treat polluted water. They are characterized by ceaseless flows of organic, chemical and microbial matter, followed by treatment steps before environmental release. WWTPs are hotspots of horizontal gene transfer between bacteria via...... conjugative plasmids, leading to dissemination of potentially hazardous genetic material such as antimicrobial resistance genes (AMRGs). While current focus is on the threat of AMRGs spreading and their environmental maintenance, conjugative plasmid transfer dynamics within and between bacterial communities...... still remains largely uncharted. Furthermore, current in vitro methods used to assess conjugation in complex microbiomes do not include in situ behaviours of recipient cells, resulting in partial understanding of transfers. We investigated the in vitro conjugation capacities of WWTP microbiomes from...

  9. Design and Application of Antimicrobial Peptide Conjugates

    Directory of Open Access Journals (Sweden)

    Andre Reinhardt

    2016-05-01

    Full Text Available Antimicrobial peptides (AMPs are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry.

  10. Energetic Tuning in Spirocyclic Conjugated Polymers

    OpenAIRE

    Hugo Bronstein; Frank D. King

    2016-01-01

    Precise control of the energy levels in a conjugated polymer is the key to allowing their exploitation in optoelectronic devices. The introduction of spirocycles into conjugated polymers has traditionally been used to enhance their solid state microstructure. Here we present a highly novel method of energetic tuning through the use of electronically active spirocyclic systems. By modifying the size and oxidation state of a heteroatom in an orthogonal spirocycle we demonstrate energetic fine t...

  11. Two-zone double phase conjugate mirror

    Science.gov (United States)

    Belić, M. R.; Vujić, D.; Sandfuchs, O.; Kaiser, F.

    2001-10-01

    An analysis of photorefractive (PR) oscillators consisting of two facing four-wave mixing regions is carried out. The threshold and operation conditions of different phase conjugate mirrors are discussed with the help of the grating action method. In particular, the threshold and the operation of the two-zone double phase conjugate mirror (DPCM) is compared with other related PR oscillators, the interconnected ring, and different connected DPCM.

  12. Rapid modification of retroviruses using lipid conjugates

    International Nuclear Information System (INIS)

    Mukherjee, Nimisha G; Le Doux, Joseph M; Andrew Lyon, L

    2009-01-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  13. Syntheses of conjugated polymers for photonics

    Czech Academy of Sciences Publication Activity Database

    Výprachtický, Drahomír; Cimrová, Věra; Kmínek, Ivan; Pavlačková, Petra

    2010-01-01

    Roč. 295, č. 1 (2010), s. 94-99 ISSN 1022-1360. [Prague Meetings on Macromolecules /73./ New Frontiers in Macromolecular Science: From Macromolecular Concepts of Living Matter to Polymers for Better Quality of Life. Prague, 05.07.2009-09.07.2009] R&D Projects: GA MŠk(CZ) 1M06031 Institutional research plan: CEZ:AV0Z40500505 Keywords : cis and trans isomers * conjugated polymer * conjugated polyelectrolyte Subject RIV: BM - Solid Matter Physics ; Magnetism

  14. Conjugation in Gram-Positive Bacteria.

    Science.gov (United States)

    Goessweiner-Mohr, Nikolaus; Arends, Karsten; Keller, Walter; Grohmann, Elisabeth

    2014-08-01

    Conjugative transfer is the most important means of spreading antibiotic resistance and virulence factors among bacteria. The key vehicles of this horizontal gene transfer are a group of mobile genetic elements, termed conjugative plasmids. Conjugative plasmids contain as minimum instrumentation an origin of transfer (oriT), DNA-processing factors (a relaxase and accessory proteins), as well as proteins that constitute the trans-envelope transport channel, the so-called mating pair formation (Mpf) proteins. All these protein factors are encoded by one or more transfer (tra) operons that together form the DNA transport machinery, the Gram-positive type IV secretion system. However, multicellular Gram-positive bacteria belonging to the streptomycetes appear to have evolved another mechanism for conjugative plasmid spread reminiscent of the machinery involved in bacterial cell division and sporulation, which transports double-stranded DNA from donor to recipient cells. Here, we focus on the protein key players involved in the plasmid spread through the two different modes and present a new secondary structure homology-based classification system for type IV secretion protein families. Moreover, we discuss the relevance of conjugative plasmid transfer in the environment and summarize novel techniques to visualize and quantify conjugative transfer in situ.

  15. Conformation and energy transfer in single conjugated polymers.

    Science.gov (United States)

    Bolinger, Joshua C; Traub, Matthew C; Brazard, Johanna; Adachi, Takuji; Barbara, Paul F; Vanden Bout, David A

    2012-11-20

    In contrast to the detailed understanding of inorganic materials, researchers lack a comprehensive view of how the properties of bulk organic materials arise from their individual components. For conjugated polymers to eventually serve as low cost semiconductor layers in electronic devices, researchers need to better understand their functionality. For organics, traditional materials science measurements tend to destroy the species of interest, especially at low concentrations. However, fluorescence continues to be a remarkably flexible, relatively noninvasive tool for probing the properties of individual molecules and allows researchers to carry out a broad range of experiments based on a relatively simple concept. In addition, the sensitivity of single-molecule spectroscopy allows researchers to see the properties of an individual component that would be masked in the bulk phase. In this Account, we examine several photophysical properties of different conjugated polymers using single-molecule spectroscopy. In these experiments, we probed the relationship between the conformation of single conjugated polymer chains and the distance scale and efficiency of energy transfer within the polymer. Recent studies used polarization anisotropy measurements on single polymer chains to study chain folding following spin-casting from solution. This Account summarizes the effects of monomer regioregularity and backbone rigidity, by comparing a regiorandom phenylene vinylene (MEH-PPV) with both a regiorandom and regioregular thiophene (P3HT). Synthesis of novel polymers allowed us to explore the role of different conformation-directing inclusions in a PPV backbone. We showed that these inclusions control the conformation of individual chains and that molecular dynamics can predict these structural effects. In situ solvent vapor annealing studies explored the dynamics of polymer chains as well as the effect of solvent evaporation on the structural equilibrium of the polymer. We

  16. Biosynthesis of Conjugate Vaccines Using an O-Linked Glycosylation System

    Directory of Open Access Journals (Sweden)

    Chao Pan

    2016-04-01

    Full Text Available Conjugate vaccines are known to be one of the most effective and safest types of vaccines against bacterial pathogens. Previously, vaccine biosynthesis has been performed by using N-linked glycosylation systems. However, the structural specificity of these systems for sugar substrates has hindered their application. Here, we report a novel protein glycosylation system (O-linked glycosylation via Neisseria meningitidis that can transfer virtually any glycan to produce a conjugate vaccine. We successfully established this system in Shigella spp., avoiding the construction of an expression vector for polysaccharide synthesis. We further found that different protein substrates can be glycosylated using this system and that the O-linked glycosylation system can also effectively function in other Gram-negative bacteria, including some strains whose polysaccharide structure was not suitable for conjugation using the N-linked glycosylation system. The results from a series of animal experiments show that the conjugate vaccine produced by this O-linked glycosylation system offered a potentially protective antibody response. Furthermore, we elucidated and optimized the recognition motif, named MOOR, for the O-glycosyltransferase PglL. Finally, we demonstrated that the fusion of other peptides recognized by major histocompatibility complex class II around MOOR had no adverse effects on substrate glycosylation, suggesting that this optimized system will be useful for future vaccine development. Our results expand the glycoengineering toolbox and provide a simpler and more robust strategy for producing bioconjugate vaccines against a variety of pathogens.

  17. Glutathione S-conjugates as prodrugs to target drug-resistant tumors

    Directory of Open Access Journals (Sweden)

    Emma E. Ramsay

    2014-08-01

    Full Text Available Living organisms are continuously exposed to xenobiotics. The major phase of enzymatic detoxification in many species is the conjugation of activated xenobiotics to reduced glutathione (GSH catalyzed by the glutathione-S-transferase (GST. It has been reported that some compounds, once transformed into glutathione S-conjugates, enter the mercapturic acid pathway whose end products are highly reactive and toxic for the cell responsible for their production. The cytotoxicity of these GSH conjugates depends essentially on GST and γ-glutamyl transferases (γGT, the enzymes which initiate the mercapturic acid synthesis pathway. Numerous studies support the view that the expression of GST and γGT in cancer cells represents an important factor in the appearance of a more aggressive and resistant phenotype. High levels of tumor GST and γGT expression were employed to selectively target tumor with GST- or γGT-activated drugs. This strategy, explored over the last two decades, has recently been successful using GST-activated nitrogen mustard (TLK286 and γGT-activated arsenic-based (GSAO and Darinaparsin prodrugs confirming the potential of GSH-conjugates as anticancer drugs.

  18. Cross-conjugation and quantum interference: a general correlation?

    DEFF Research Database (Denmark)

    Valkenier, Hennie; Guedon, Constant M.; Markussen, Troels

    2014-01-01

    -conjugation patterns, but identical lengths, i.e. an anthracene (linear conjugation), an anthraquinone (cross-conjugation), and a dihydroanthracene (broken conjugation) derivative. To benchmark reliable trends, conductance experiments on these series have been performed by various techniques. Here, we compare data...... characterized by beta = 0.37 +/- 0.03 angstrom(-1) (CP-AFM). Remarkably, for the second series, we do not only find that the linearly conjugated anthracene-containing wire is the most conductive, but also that the cross-conjugated anthraquinone-containing wire is less conductive than the broken...

  19. Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Eudes, Aymerick [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mouille, Maxence [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Robinson, David S. [Joint BioEnergy Institute, Emeryville, CA (United States); Benites, Veronica T. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); San Francisco State Univ., San Francisco, CA (United States); Wang, George [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Roux, Lucien [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Ecole Polytechnique Federale de Lausanne, Lausanne (Switzerland); Tsai, Yi-Lin [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Baidoo, Edward E. K. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Chiu, Tsan-Yu [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Heazlewood, Joshua L. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); The Univ. of Melbourne, Melbourne, VIC (Australia); Scheller, Henrik V. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mukhopadhyay, Aindrila [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Keasling, Jay D. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Technical Univ. of Denmark, Horsholm (Denmark); Deutsch, Samuel [Joint BioEnergy Institute, Emeryville, CA (United States); Loqué, Dominique [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. Claude Bernard Lyon 1, Villeurbanne (France)

    2016-11-21

    BAHD acyltransferases, named after the first four biochemically characterized enzymes of the group, are plant-specific enzymes that catalyze the transfer of coenzyme A-activated donors onto various acceptor molecules. They are responsible for the synthesis in plants of a myriad of secondary metabolites, some of which are beneficial for humans either as therapeutics or as specialty chemicals such as flavors and fragrances. The production of pharmaceutical, nutraceutical and commodity chemicals using engineered microbes is an alternative, green route to energy-intensive chemical syntheses that consume petroleum-based precursors. However, identification of appropriate enzymes and validation of their functional expression in heterologous hosts is a prerequisite for the design and implementation of metabolic pathways in microbes for the synthesis of such target chemicals. As a result, for the synthesis of valuable metabolites in the yeast Saccharomyces cerevisiae, we selected BAHD acyltransferases based on their preferred donor and acceptor substrates. In particular, BAHDs that use hydroxycinnamoyl-CoAs and/or benzoyl-CoA as donors were targeted because a large number of molecules beneficial to humans belong to this family of hydroxycinnamate and benzoate conjugates. The selected BAHD coding sequences were synthesized and cloned individually on a vector containing the Arabidopsis gene At4CL5, which encodes a promiscuous 4-coumarate:CoA ligase active on hydroxycinnamates and benzoates. The various S. cerevisiae strains obtained for co-expression of At4CL5 with the different BAHDs effectively produced a wide array of valuable hydroxycinnamate and benzoate conjugates upon addition of adequate combinations of donors and acceptor molecules. In particular, we report here for the first time the production in yeast of rosmarinic acid and its derivatives, quinate hydroxycinnamate esters such as chlorogenic acid, and glycerol hydroxycinnamate esters

  20. Photoresponsive switches at surfaces based on supramolecular functionalization with azobenzene-oligoglycerol conjugates.

    Science.gov (United States)

    Nachtigall, Olaf; Kördel, Christian; Urner, Leonhard H; Haag, Rainer

    2014-09-01

    The synthesis, supramolecular complexation, and switching of new bifunctional azobenzene-oligoglycerol conjugates in different environments is reported. Through the formation of host-guest complexes with surface immobilized β-cyclodextrin receptors, the bifunctional switches were coupled to gold surfaces. The isomerization of the amphiphilic azobenzene derivatives was examined in solution, on gold nanoparticles, and on planar gold surfaces. The wettability of functionalized gold surfaces can be reversibly switched under light-illumination with two different wavelengths. Besides the photoisomerization processes and concomitant effects on functionality, the thermal cis to trans isomerization of the conjugates and their complexes was monitored. Thermal half-lives of the cis isomers were calculated for different environments. Surprisingly, the half-lives on gold nanoparticles were significantly smaller compared to planar gold surfaces. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Photochemical immobilization of anthraquinone conjugated oligonucleotides and PCR amplicons on solid surfaces

    DEFF Research Database (Denmark)

    Koch, T.; Jacobsen, N.; Fensholdt, J.

    2000-01-01

    Ligand immobilization on solid surfaces is an essential step in fields such as diagnostics, bio sensor manufacturing, and new material sciences in general. In this paper a photochemical approach based on anthraquinone as the chromophore is presented. Photochemical procedures offer special...... advantages as they are able to generate highly reactive species in an orientation specific manner. As presented here, anthraquinone (AQ) mediated covalent DNA immobilization appears to be superior to currently known procedures. A synthetic procedure providing AQ-phosphoramidites is presented. These reagents...... facilitate AQ conjugation during routine DNA synthesis, thus enabling the AQ-oligonucleotides to be immobilized in a very convenient and efficient manner. AQ-conjugated PCR primers can be used directly in PCR. When the PCR is performed in solution, the amplicons can be immobilized after the PCR. Moreover...

  2. A palladium-catalysed multicomponent coupling approach to conjugated poly(1,3-dipoles) and polyheterocycles

    Science.gov (United States)

    Leitch, David C.; Kayser, Laure V.; Han, Zhi-Yong; Siamaki, Ali R.; Keyzer, Evan N.; Gefen, Ashley; Arndtsen, Bruce A.

    2015-06-01

    Conjugated polymers have emerged over the past several decades as key components for a range of applications, including semiconductors, molecular wires, sensors, light switchable transistors and OLEDs. Nevertheless, the construction of many such polymers, especially highly substituted variants, typically involves a multistep synthesis. This can limit the ability to both access and tune polymer structures for desired properties. Here we show an alternative approach to synthesize conjugated materials: a metal-catalysed multicomponent polymerization. This reaction assembles multiple monomer units into a new polymer containing reactive 1,3-dipoles, which can be modified using cycloaddition reactions. In addition to the synthetic ease of this approach, its modularity allows easy adaptation to incorporate a range of desired substituents, all via one-pot reactions.

  3. Novel nature-inspired conjugated polymers for high performance transistors and solar cells (Presentation Recording)

    Science.gov (United States)

    Bronstein, Hugo A.; Falon, Kealan; Yaacobi-Gross, Nir; Ashraf, Raja Shahid; McCulloch, Iain; Anthopoulos, Thomas D.

    2015-10-01

    Novel, extremely narrow band-gap polymer with a structure based on natural indigo has been synthesised and exhibits high crystallinity, high ambipolar transport in OFET devices, and OPV device efficiencies up to 2.35% with light absorbance up to 950 nm, demonstrating potential in near-IR photovoltaics. We demonstrate that the use of a potentially bio-sustainable monomer unit in a conjugated polymer can give balanced ambipolar OFET mobilities in excess of 0.5 cm2/Vs. This novel monomer, and polymers are synthesized by rigidifying the structure of indigo by condensation with an aromatic acidic acid. The materials display high crystallinity which can be further enhanced by annealing and demonstrate that it can be used as a potentially biosustainable alternative to the commonly used DPP and iso-indigo monomers. We believe this is the first attempt to tackle the issue of sustainability in conjugated polymer synthesis.

  4. Phase conjugate Michelson interferometer for optical logic

    Science.gov (United States)

    Khoury, Jed

    2017-05-01

    The interference theory is developed for of the phase conjugate Michelson interferometer in which its ordinary mirrors are replaced by a single externally pumped phase conjugate mirror. According to the theory, it was found that for an interferometer with two equal arms, the path length difference depends solely on the initial alignment of the two input beams, and the vertical alignment readout. Small vertical misalignments in the readout beam by mrad causes a huge change in the phase difference in the phase between the two interferometer arms beam. The phase difference is proportional to the interferometer arm lengths. The overlap between the phase conjugate beams is not affected by the interferometer beam alignment. The interferometer is proposed for nondestructive testing and the design all optical logic and associated fuzzy logic for ultrafast optical pattern recognition.

  5. Tight-binding treatment of conjugated polymers

    DEFF Research Database (Denmark)

    Lynge, Thomas Bastholm

    This PhD thesis concerns conjugated polymers which constitute a constantly growing research area. Today, among other things, conjugated polymers play a role in plastic based solar cells, photodetectors and light emitting diodes, and even today such plastic-based components constitute an alternative...... of tomorrow. This thesis specifically treats the three conjugated polymers trans-polyacetylene (tPA), poly(para-phenylene) (PPP) and poly(para-phe\\-nylene vinylene) (PPV). The present results, which are derived within the tight-binding model, are divided into two parts. In one part, analytic results...... are derived for the optical properties of the polymers expressed in terms of the optical susceptibility both in the presence and in the absence of a static electric field. In the other part, the cumputationally efficient Density Functional-based Tight-Binding (DFTB) model is applied to the description...

  6. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Miller

    2011-01-01

    Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

  7. Nonlinear conjugate gradient methods in micromagnetics

    Directory of Open Access Journals (Sweden)

    J. Fischbacher

    2017-04-01

    Full Text Available Conjugate gradient methods for energy minimization in micromagnetics are compared. The comparison of analytic results with numerical simulation shows that standard conjugate gradient method may fail to produce correct results. A method that restricts the step length in the line search is introduced, in order to avoid this problem. When the step length in the line search is controlled, conjugate gradient techniques are a fast and reliable way to compute the hysteresis properties of permanent magnets. The method is applied to investigate demagnetizing effects in NdFe12 based permanent magnets. The reduction of the coercive field by demagnetizing effects is μ0ΔH = 1.4 T at 450 K.

  8. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Science.gov (United States)

    Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela

    2011-01-01

    Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles. PMID:21991444

  9. Serogroup A meningococcal conjugate vaccines in Africa.

    Science.gov (United States)

    Kristiansen, Paul A; Jørgensen, Hannah J; Caugant, Dominique A

    2015-01-01

    Serogroup A meningococcal epidemics have been a recurrent public health problem, especially in resource-poor countries of Africa. Recently, the administration in mass vaccination campaigns of a single dose of the monovalent meningococcal conjugate vaccine, MenAfriVac, to the 1-29 year-old population of sub-Saharan Africa has prevented epidemics of meningitis caused by serogroup A Neisseria meningitidis. This strategy has also been shown to provide herd protection of the non-vaccinated population. Development of meningococcal conjugate vaccines covering other serogroups and enhanced use of the pneumococcal and Haemophilus influenzae type b conjugate vaccines must be pursued to fully control bacterial meningitis in sub-Saharan Africa.

  10. Conjugate gradient algorithms using multiple recursions

    Energy Technology Data Exchange (ETDEWEB)

    Barth, T.; Manteuffel, T.

    1996-12-31

    Much is already known about when a conjugate gradient method can be implemented with short recursions for the direction vectors. The work done in 1984 by Faber and Manteuffel gave necessary and sufficient conditions on the iteration matrix A, in order for a conjugate gradient method to be implemented with a single recursion of a certain form. However, this form does not take into account all possible recursions. This became evident when Jagels and Reichel used an algorithm of Gragg for unitary matrices to demonstrate that the class of matrices for which a practical conjugate gradient algorithm exists can be extended to include unitary and shifted unitary matrices. The implementation uses short double recursions for the direction vectors. This motivates the study of multiple recursion algorithms.

  11. CO-releasing molecule (CORM) conjugate systems.

    Science.gov (United States)

    Kautz, Anna Christin; Kunz, Peter C; Janiak, Christoph

    2016-11-15

    The development of CORMs (CO-releasing molecules) as a prodrug for CO administration in living organisms has attracted significant attention. CORMs offer the promising possibility of a safe and controllable release of CO in low amounts triggered by light, ligands, enzymes, etc. For the targeting of specific tissues or diseases and to prevent possible side effects from metals and other residues after CO release, these CORMs are attached to biocompatible systems, like peptides, polymers, nanoparticles, dendrimers, protein cages, non-wovens, tablets, and metal-organic frameworks. We discuss in this review the known CORM carrier conjugates, in short CORM conjugates, with covalently-bound or incorporated CORMs for medicinal and therapeutic applications. Most conjugates are nontoxic, show increasing half-lives of CO release, and make use of the EPR-effect, but still show problems because of a continuous background of CO release and the absence of an on/off-switch for the CO release.

  12. Comparison of the formation of nicotinic acid conjugates in leaves of different plant species.

    Science.gov (United States)

    Ashihara, Hiroshi; Yin, Yuling; Katahira, Riko; Watanabe, Shin; Mimura, Tetsuro; Sasamoto, Hamako

    2012-11-01

    There are three metabolic fates of nicotinic acid in plants: (1) nicotinic acid mononucleotide formation for NAD synthesis by the so-called salvage pathway of pyridine nucleotide biosynthesis; (2) nicotinic acid N-glucoside formation; and (3) trigonelline (N-methylnicotinic acid) formation. In the present study, the metabolism of [carbonyl-(14)C]nicotinamide was investigated in leaves of 23 wild plant species. All species readily converted nicotinamide to nicotinic acid, and only a fraction of nicotinic acid was utilised for NAD and NADP synthesis. The remaining nicotinic acid is converted to the nicotinic acid conjugates. Only one plant species, Cycas revoluta, produced both nicotinic acid N-glucoside and trigonelline; the other 22 species produced one or other of the conjugates. The nicotinic acid N-glucoside-forming plants are Cyathea lepifera, Arenga trewmula var. englri, Barringtonia racemosa, Ilex paraguariensis, Angelica japonica, Scaevola taccada and Farfugium japonicum. In contrast, trigonelline is formed in C. lepifera, Ginkgo biloba, Pinus luchuensis, Casuarina equisetifolia, Alocasia odora, Pandanus odoratissimus, Hylocereus undatus, Kalanchoe pinnata, Kalanchoe tubiflora, Populus alba, Garcinia subelliptica, Oxalis corymbosa, Leucaena leucocephala, Vigna marina, Hibiscus tiliaceus and Melicope triphylla. The diversity of nicotinic acid conjugate formation in plants is discussed using these results and our previous investigation involving a few model plants, various crops and ferns. Nicotinic acid N-glucoside formation was restricted mostly to ferns and selected orders of angiosperms, whereas other plants produce trigonelline. In most cases the formation of both nicotinic acid conjugates is incompatible, but some exceptions have been found. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  13. Conjugated Polymers as Actuators: Modes of Actuation

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2004-01-01

    The physical and chemical properties of conjugated polymers often depend very strongly on the degree of doping with anions or cations. The movement of ions in and out of the polymer matrix as it is redox cycled is also accompanied by mechanical changes. Both the volume and the stiffness can exhibit...... significant differences between the oxidized and reduced states. These effects form the basis of the use of conjugated polymers as actuators (or “artificial muscles”) controllable by a small (1-10 V) voltage. Three basic modes of actuation (bending, linear extension and stiffness change) have been proposed...

  14. Functionalized conjugated polyelectrolytes design and biomedical applications

    CERN Document Server

    Wang, Shu

    2014-01-01

    Functionalized Conjugated Polyelectrolytes presents a comprehensive review of these polyelectrolytes and their biomedical applications. Basic aspects like molecular design and optoelectronic properties are covered in the first chapter. Emphasis is placed on the various applications including sensing (chemical and biological), disease diagnosis, cell imaging, drug/gene delivery and disease treatment. This book explores a multi-disciplinary topic of interest to researchers working in the fields of chemistry, materials, biology and medicine. It also offers an integrated perspective on both basic research and application issues. Functionalized conjugated polyelectrolyte materials, which have already drawn considerable interest, will become a major new direction for biomedicine development.

  15. Conjugated polymers as actuators: modes of actuation

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2007-01-01

    The physical and chemical properties of conjugated polymers often depend very strongly on the degree of doping with anions or cations. The movement of ions in and out of the polymer matrix as it is redox cycled is also accompanied by mechanical changes. Both the volume and the stiffness can exhibit...... significant differences between the oxidized and reduced states. These effects form the basis of the use of conjugated polymers as actuators (or “artificial muscles”) controllable by a small (1-10 V) voltage. Three basic modes of actuation (bending, linear extension and stiffness change) have been proposed...

  16. Folic Acid-Conjugated Pyropheophorbide a as the Photosensitizer Tested for In Vivo Targeted Photodynamic Therapy.

    Science.gov (United States)

    Wang, Jin; Liu, Qian; Zhang, Yuting; Shi, Huan; Liu, Hui; Guo, Wenjun; Ma, Yanhong; Huang, Weiqiang; Hong, Zhangyong

    2017-06-01

    Photodynamic therapy (PDT) is a highly localized and minimally invasive cancer treatment modality with many important advantages, but the lack of ideal photosensitizers (PSs) greatly restricts its clinical utility. To develop new PSs with highly efficient singlet oxygen production and high tumor-localizing ability to reduce damage to healthy adjacent tissues, we conjugated folic acid (FA) with pyropheophorbide a (Pyro), a potent PS with a very high singlet oxygen quantum yield and a high extinction coefficient. In the present work, we describe the synthesis and PDT evaluation of this FA-Pyro conjugate both in vitro and in vivo. This conjugation increased the accumulation of Pyro inside the tumors and improved the efficiency of PDT, resulting in eradication of subcutaneous xenograft KB (human mouth epidermal carcinoma) tumors after only 1 or 2 applications of external near infrared light irradiation. This outstanding PDT outcome in a tumor-bearing mouse model and the simple synthesis of the conjugate should have very good practical potential for clinical application. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  17. De-conjugation behavior of conjugated estrogens in the raw sewage, activated sludge and river water.

    Science.gov (United States)

    Kumar, Vimal; Johnson, Andrew C; Nakada, Norihide; Yamashita, Naoyuki; Tanaka, Hiroaki

    2012-08-15

    The fate and behavior of estrone-3-sulfate (E1-3S), estradiol-3-sulfate (E2-3S), estrone-3-glucuronide (E1-3G) and estradiol-3-glucuronide (E2-3G) were studied in raw sewage, activated sludge and river water using microcosms. The glucuronide conjugates had a half-life of 0.4h in raw sewage, yielding 40-60% of their free estrogens. Field observations at three activated sludge processes suggested complete transformation of the glucuronide conjugates in the sewer. In river water glucuronide conjugates half-lives extended to over 2d yielding 60-100% of their free parent estrogens. Transformation of the sulfate conjugates in raw sewage and river water was slow with little formation of the parent estrogens. Sulfate conjugates could readily be detected in sewage influent in the field studies. In activated sludge the sulfate conjugates had half-lives of 0.2h with the transient formation of 10-55% of the free parent estrogens. Field studies indicated transformation of sulfate conjugates across the sewage treatment, although a proportion escaped into the effluent. These results broadly support the view that glucuronide conjugates will be entirely transformed within the sewer largely to their parent estrogens. The sulfate conjugates may persist in raw sewage and river water but are transformable in activated sludge and, in the case of E2-3S, reform a high proportion of the parent estrogen. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Multistep Synthesis of a Terphenyl Derivative Showcasing the Diels-Alder Reaction

    Science.gov (United States)

    Davie, Elizabeth A. Colby

    2015-01-01

    An adaptable multistep synthesis project designed for the culmination of a second-year organic chemistry laboratory course is described. The target compound is a terphenyl derivative that is an intermediate in the synthesis of compounds used in organic light-emitting devices. Students react a conjugated diene with dimethylacetylene dicarboxylate…

  19. A sequential high-yielding large-scale solution-method for synthesis of philanthotoxin analogues

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Jaroszewski, Jerzy W; Hansen, Steen Honoré

    2003-01-01

    A general, improved procedure for rapid synthesis of philanthotoxin analogues, a pharmacologically important class of polyamine conjugates, is described. The solution-phase procedure is illustrated by gram-scale synthesis of philanthotoxins PhTX-343 and PhTX-12. Selectively protected polyamines...

  20. Conjugation fidelity of double phase-conjugate mirrors in photorefractive materials with two-center transport.

    Science.gov (United States)

    Geri, I; Ozkul, C

    1996-11-01

    The temporal evolution of double phase-conjugate mirrors (DPCM's) in photorefractive materials such as BaTiO(3):Co:Fe is studied by use of the plane-wave expansion method. The buildup time of DPCM and its conjugation fidelity are compared with those of photorefractive materials with a single-center transport. Numerical simulations show that one can decrease the threshold value of the coupling strength required for the DPCM operation with a high conjugation fidelity by doping the BaTiO(3) crystals weakly with Co in comparison with undoped crystals.

  1. Safety and Efficacy of Dextran-Rosmarinic Acid Conjugates as Innovative Polymeric Antioxidants in Skin Whitening: What Is the Evidence?

    Directory of Open Access Journals (Sweden)

    Ortensia I. Parisi

    2017-08-01

    Full Text Available Background: Melanins are high molecular weight pigments responsible for the mammalian skin and hair colour and play a key role in skin protection from UV radiation; however, their overproduction and excessive accumulation lead to pigmentation problems including melasma, freckles, uneven colouring, and age spots. Therefore, the modulation of melanin synthesis represents a critical issue in medicine and cosmetology. In the present study, an innovative polymeric antioxidant to be used as skin whitening agent is developed by the conjugation of dextran with rosmarinic acid. Methods: Dextran-rosmarinic acid conjugates (DEX-RA were synthesized in a one-pot method starting from Origanum vulgare aqueous leaf extract and dextran. The total polyphenol content and the antioxidant activity were assessed by Folin-Ciocalteau assay and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH and bleaching tests, respectively. The efficacy of DEX-RA was evaluated by inhibition of tyrosinase activity, in vitro diffusion and stability studies and in vivo studies. The biocompatibility of the conjugates was investigated by 3-[4,5-Dimethylthiaoly]-2,5-diphenyltetrazoliumbromide (MTT and EPISKIN™ model. Results: Efficacy and safety studies confirmed the antioxidant and tyrosinase inhibitory activities and the biocompatibility of the synthesized conjugates. Conclusion: The polymeric conjugates, comparing to the free antioxidant, show a long-lasting efficacy combined to an enhanced stability resulting in an improved performance of the cosmetic formulations prepared using this innovative whitening agent as a bioactive ingredient.

  2. Brain-Eating Amoebae: Silver Nanoparticle Conjugation Enhanced Efficacy of Anti-Amoebic Drugs against Naegleria fowleri.

    Science.gov (United States)

    Rajendran, Kavitha; Anwar, Ayaz; Khan, Naveed Ahmed; Siddiqui, Ruqaiyyah

    2017-12-20

    The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against primary amoebic meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV-visible spectrophotometry. Atomic force microscopy determined their size in range of 20-100 nm. To determine amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiamoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiamoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying existing drugs to enhance their antiamoebic effects is a useful avenue that holds promise in improving the treatment of brain-eating amoebae infection due to N. fowleri.

  3. New Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1 for Anti-Vascular Targeted Photodynamic Therapy.

    Science.gov (United States)

    Kamarulzaman, Ezatul Ezleen; Gazzali, Amirah Mohd; Acherar, Samir; Frochot, Céline; Barberi-Heyob, Muriel; Boura, Cédric; Chaimbault, Patrick; Sibille, Estelle; Wahab, Habibah A; Vanderesse, Régis

    2015-10-12

    Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated along with in vitro and in vivo stability levels. The tissue concentration of the TPC-conjugates in animal model shows good distribution, especially for the DKPPR conjugates. The novel peptide-PS conjugates proposed in this study were proven to have potential to be further developed as future NRP-1 targeting photodynamic therapy agent.

  4. Nanomolar cellular antisense activity of peptide nucleic acid (PNA) cholic acid ("umbrella") and cholesterol conjugates delivered by cationic lipids.

    Science.gov (United States)

    Shiraishi, Takehiko; Nielsen, Peter E

    2012-02-15

    Limited cellular uptake and low bioavailability of peptide nucleic acids (PNAs) have restricted widespread use of PNAs as antisense/antigene agents for cells in culture and not least for in vivo applications. We now report the synthesis and cellular antisense activity in cultured HeLa pLuc705 cells of cholesterol and cholic acid ("umbrella") derivatives of splice correction antisense PNA oligomers. While the conjugates alone were practically inactive up to 1 μM, their activity was dramatically improved when delivered by a cationic lipid transfection agent (LipofectAMINE2000). In particular, PNAs, conjugated to cholesterol through an ester hemisuccinate linker or to cholic acid, exhibited low nanomolar activity (EC(50) ∼ 25 nM). Excellent sequence specificity was retained, as mismatch PNA conjugates did not show any significant antisense activity. Furthermore, we show that increasing the transfection volume improved transfection efficiency, suggesting that accumulation (condensation) of the PNA/lipid complex on the cellular surface is part of the uptake mechanism. These results provide a novel, simple method for very efficient cellular delivery of PNA oligomers, especially using PNA-cholic acid conjugates which, in contrast to PNA-cholesterol conjugates, exhibit sufficient water solubility. The results also question the generality of using cholic acid "umbrella" derivatives as a delivery modality for antisense oligomers.

  5. Efficient Xerographic Photoreceptors from Conjugated Polymers and Polymer Blends

    National Research Council Canada - National Science Library

    Zhang, Xuejun, Ph.D

    1998-01-01

    Bilayer xerographic photoreceptors in which pi-conjugated polymers and binary conjugated polymer blends are used as the charge generation layer have been fabricated, evaluated, and shown to be highly efficient...

  6. Highly Potent Antibacterial Organometallic Peptide Conjugates.

    Science.gov (United States)

    Albada, Bauke; Metzler-Nolte, Nils

    2017-10-17

    Resistance of pathogenic bacteria against currently marketed antibiotics is again increasing. To meet the societal need for effective cures, scientists are faced with the challenge of developing more potent but equally bacteria-specific drugs. Currently, most efforts are directed toward the modification of existing antibiotics, but ideally, compounds with a new mode of action are required. In this Account, we detail our findings in the area of novel metal-based antibiotics. Our strategy is based on the modification of simple antimicrobial peptides (AMPs) with organometallic agents, resulting in organometallic AMPs (OM-AMPs). Since bacteria have most likely never encountered these synthetically prepared unnatural organometallic agents, we anticipated that such agents could well become potentiating players in the antibiotics arena. Moreover, exploiting some of the particular properties of metal complexes should also help to elucidate the mode of action of small cationic AMPs, the molecular details of which have remained elusive despite intensive efforts. Using standard Fmoc/tBu-based solid-phase peptide synthesis approaches, we have prepared various organometallic-peptide conjugates with covalently linked group 8 and 9 metallocenes (ferrocene, ruthenocene, osmocene, and cobaltocenium). As a starting point we took the (RW) 3 antibacterial hexapeptide lead structure. After modifying the peptide sequence (generations 1 and 2), changing the nature and position of the organometallic group (generation 3), and optimizing the amino acid chirality (generation 5), we identified several organometallic antibacterial peptides that are currently among the most active synthetic AMPs (synAMPs) that have ever been prepared. Through these rational and systematic optimizations, we were able to increase the antibacterial activity of a short non-organometallic synAMP 18-fold to submicromolar activity, rivaling the activity of vancomycin (often the drug of last resort) against methicillin

  7. Functional analysis of the conjugation system from Clostridium perfringens

    OpenAIRE

    Wisniewski, Jessica Ann

    2017-01-01

    In Clostridium perfringens, toxins that cause histotoxic and gastrointestinal diseases have been identified on a family of large conjugative plasmids. The tcp transfer locus was initially identified on the prototype conjugative plasmid, pCW3. This locus has been shown to mediate conjugative plasmid transfer and studies on several of the Tcp proteins have identified their role in plasmid transfer. In general less is known about the mechanism of conjugative transfer in Gram positive bacteria, n...

  8. Women experiencing the intergenerationality of conjugal violence

    Directory of Open Access Journals (Sweden)

    Gilvânia Patrícia do Nascimento Paixão

    2015-10-01

    Full Text Available Objective: to analyze the family relationship, in childhood and adolescence, of women who experience conjugal violence.Method: qualitative study. Interviews were held with 19 women, who were experiencing conjugal violence, and who were resident in a community in Salvador, Bahia, Brazil. The project was approved by the Research Ethics Committee (N. 42/2011.Results: the data was organized using the Discourse of the Collective Subject, identifying the summary central ideas: they witnessed violence between their parents; they suffered repercussions from the violence between their parents: they were angry about the mother's submission to her partner; and they reproduced the conjugal violence. The discourse showed that the women witnessed, in childhood and adolescence, violence between their parents, and were injured both physically and psychologically. As a result of the mother's submission, feelings of anger arose in the children. However, in the adult phase of their own lives, they noticed that their conjugal life resembled that of their parents, reproducing the violence.Conclusion: investment is necessary in strategies designed to break inter-generational violence, and the health professionals are important in this process, as it is a phenomenon with repercussions in health. Because they work in the Family Health Strategy, which focuses on the prevention of harm and illness, health promotion and interdepartmentality, the nurses are essential in the process of preventing and confronting this phenomenon.

  9. Women experiencing the intergenerationality of conjugal violence.

    Science.gov (United States)

    Paixão, Gilvânia Patrícia do Nascimento; Gomes, Nadirlene Pereira; Diniz, Normélia Maria Freire; Carvalho e Lira, Margaret Ollinda de Souza; Carvalho, Milca Ramaiane da Silva; da Silva, Rudval Souza

    2015-01-01

    to analyze the family relationship, in childhood and adolescence, of women who experience conjugal violence. qualitative study. Interviews were held with 19 women, who were experiencing conjugal violence, and who were resident in a community in Salvador, Bahia, Brazil. The project was approved by the Research Ethics Committee (N. 42/2011). the data was organized using the Discourse of the Collective Subject, identifying the summary central ideas: they witnessed violence between their parents; they suffered repercussions from the violence between their parents: they were angry about the mother's submission to her partner; and they reproduced the conjugal violence. The discourse showed that the women witnessed, in childhood and adolescence, violence between their parents, and were injured both physically and psychologically. As a result of the mother's submission, feelings of anger arose in the children. However, in the adult phase of their own lives, they noticed that their conjugal life resembled that of their parents, reproducing the violence. investment is necessary in strategies designed to break inter-generational violence, and the health professionals are important in this process, as it is a phenomenon with repercussions in health. Because they work in the Family Health Strategy, which focuses on the prevention of harm and illness, health promotion and interdepartmentality, the nurses are essential in the process of preventing and confronting this phenomenon.

  10. Unsymmetrical extended -conjugated zinc phthalocyanine for ...

    Indian Academy of Sciences (India)

    We have designed and synthesized a new unsymmetrical zinc phthalocyanine based on `push-pull' and extended -conjugation concept, PCH008. The new sensitizer was fully characterized by CHN anlysis, UV-Vis., fluorescence spectroscopies and cyclic voltammetry. The new sensitizer which upon anchoring onto ...

  11. Compositions for directed alignment of conjugated polymers

    Science.gov (United States)

    Kim, Jinsang; Kim, Bong-Gi; Jeong, Eun Jeong

    2016-04-19

    Conjugated polymers (CPs) achieve directed alignment along an applied flow field and a dichroic ratio of as high as 16.67 in emission from well-aligned thin films and fully realized anisotropic optoelectronic properties of CPs in field-effect transistor (FET).

  12. Theoretical study of conjugated porphyrin polymers

    DEFF Research Database (Denmark)

    Pedersen, T.G.; Lynge, T.B.; Kristensen, P.K.

    2005-01-01

    for these applications. From a theoretical analysis of excitons in long metalloporphyrin chains, we demonstrate that the binding energy is much lower than in usual conjugated polymers. Our calculated absorption spectra are in good agreement with measurements. (c) 2004 Elsevier B.V. All rights reserved....

  13. preconditioning the modified conjugate gradient method

    African Journals Online (AJOL)

    Admin

    The conventional conjugate method (CGM) was originally developed by Hestenes and. Stiefel (1952) as a method of solution for linear systems. Fletcher and Reeves (1964) built the necessary underlying theory for a successful application of the method to quadratic functional and developed its convergence properties.

  14. Ciprofloxacin conjugated zinc oxide nanoparticle: A camouflage ...

    Indian Academy of Sciences (India)

    excellent antibacterial activity against clinically isolated multidrug resistant bacterial strains of Escherichia coli,. Staphylococcus aureus and ... Keywords. Zinc oxide nanoparticles; ciprofloxacin; chemical conjugation; antibacterial property. 1. Introduction ... Nanoparticles of TiO2, ZnO, silver, etc. are commonly known for their ...

  15. Bacillus thuringiensis Conjugation in Simulated Microgravity

    Science.gov (United States)

    Beuls, Elise; van Houdt, Rob; Leys, Natalie; Dijkstra, Camelia; Larkin, Oliver; Mahillon, Jacques

    2009-10-01

    Spaceflight experiments have suggested a possible effect of microgravity on the plasmid transfer among strains of the Gram-positive Bacillus thuringiensis, as opposed to no effect recorded for Gram-negative conjugation. To investigate these potential effects in a more affordable experimental setup, three ground-based microgravity simulators were tested: the Rotating Wall Vessel (RWV), the Random Positioning Machine (RPM), and a superconducting magnet. The bacterial conjugative system consisted in biparental matings between two B. thuringiensis strains, where the transfer frequencies of the conjugative plasmid pAW63 and its ability to mobilize the nonconjugative plasmid pUB110 were assessed. Specifically, potential plasmid transfers in a 0-g position (simulated microgravity) were compared to those obtained under 1-g (normal gravity) condition in each device. Statistical analyses revealed no significant difference in the conjugative and mobilizable transfer frequencies between the three different simulated microgravitational conditions and our standard laboratory condition. These important ground-based observations emphasize the fact that, though no stimulation of plasmid transfer was observed, no inhibition was observed either. In the case of Gram-positive bacteria, this ability to exchange plasmids in weightlessness, as occurs under Earth's conditions, should be seen as particularly relevant in the scope of spread of antibiotic resistances and bacterial virulence.

  16. Conjugated Polymer Actuators: Prospects and Limitations

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2007-01-01

    Actuators constructed with a conjugated polymer as the active part have been predicted to have a number of highly desirable properties: Large mechanical strength, high power density, i.e. high actuation speeds possible, sufficient maximum strain values, high reversibility and safe, low voltages (1...

  17. Immunogenicity of novel sulfadimethoxide conjugates | Chen ...

    African Journals Online (AJOL)

    Immunogenicity of novel sulfadimethoxide conjugates. L Chen, J Su, X Zhang, L Li, X He. Abstract. Sulfadimethoxine (SDM) is an antibiotic commonly added to animal feeds. Anti-SDM antibodies are useful for the detection of residual SDM in foods, feeds and biological fluids by ELISA. In this study, we show that SDM is ...

  18. Theory of periodic conjugate heat transfer

    CERN Document Server

    Zudin, Yuri B

    2016-01-01

    This book presents the theory of periodic conjugate heat transfer in detail. It offers a simplified description of the interaction between a solid body and a fluid as a boundary value problem of the heat conduction equation for the solid body.

  19. Meningococcal conjugate vaccines: optimizing global impact

    Directory of Open Access Journals (Sweden)

    Terranella A

    2011-09-01

    Full Text Available Andrew Terranella1,2, Amanda Cohn2, Thomas Clark2 1Epidemic Intelligence Service, Division of Applied Sciences, Scientific Education and Professional Development Program Office, 2Meningitis and Vaccine Preventable Diseases Branch, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA Abstract: Meningococcal conjugate vaccines have several advantages over polysaccharide vaccines, including the ability to induce greater antibody persistence, avidity, immunologic memory, and herd immunity. Since 1999, meningococcal conjugate vaccine programs have been established across the globe. Many of these vaccination programs have resulted in significant decline in meningococcal disease in several countries. Recent introduction of serogroup A conjugate vaccine in Africa offers the potential to eliminate meningococcal disease as a public health problem in Africa. However, the duration of immune response and the development of widespread herd immunity in the population remain important questions for meningococcal vaccine programs. Because of the unique epidemiology of meningococcal disease around the world, the optimal vaccination strategy for long-term disease prevention will vary by country. Keywords: conjugate vaccine, meningitis, meningococcal vaccine, meningococcal disease

  20. Determinants of pneumococcal conjugate vaccine uptake among ...

    African Journals Online (AJOL)

    Subjects: The respondents were the parents/guardians of children less than two years of age attending immunisation services at KNH and those admitted in the peadiatric wards with pneumonia. Results: The study established that the determinants of uptake of Pneumococcal Conjugate Vaccine are age(OR 5.8, CI 1.4-23.4, ...

  1. Stabilizing cations in the backbones of conjugated polymers

    NARCIS (Netherlands)

    Voortman, Thomas P.; de Gier, Hilde D.; Havenith, Remco W. A.; Chiechi, Ryan C.

    2014-01-01

    We synthesized a cross-conjugated polymer containing ketones in the backbone and converted it to a linearly conjugated, cationic polyarylmethine via a process we call "spinless doping" to create a new class of materials, conjugated polyions. This process involves activating the ketones with a Lewis

  2. DA conjugated polymers containing substituted thiophene, 1, 3, 4 ...

    Indian Academy of Sciences (India)

    ... electron-accepting (A) 1,3,4- oxadiazole unit and non-conjugation linkers. The conjugated segment in P1-P3 contains only five aromatic rings resulting in short conjugation length, but has an alternate D-A arrangement which significantly enhances the intramolecular charge transfer (ICT) interaction within the segment.

  3. On the chemical synthesis and drug delivery response of folate receptor-activated, polyethylene glycol-functionalized magnetite nanoparticles.

    Science.gov (United States)

    Zhang, J; Rana, S; Srivastava, R S; Misra, R D K

    2008-01-01

    We describe here the chemical synthesis and in vitro drug delivery response of polyethylene glycol (PEG)-functionalized magnetite (Fe(3)O(4)) nanoparticles, which were activated with a stable ligand, folic acid, and conjugated with an anticancer drug, doxorubicin. The functionalization and conjugation steps in the chemical synthesis were confirmed using Fourier transform infrared spectroscopy. The drug-release behavior of PEG-functionalized and folic acid-doxorubicin-conjugated magnetic nanoparticles was characterized by two stages involving an initial rapid release, followed by a controlled release.

  4. Fabrication, characterization, thermal stability and nanoassemblies of novel pullulan-aspirin conjugates

    OpenAIRE

    Muhammad A. Hussain; Khawar Abbas; Bilal A. Lodhi; Muhammad Sher; Muhammad Ali; Muhammad N. Tahir; Wolfgang Tremel; Saima Iqbal

    2017-01-01

    Present study deals with homogeneous and one-pot synthesis of novel macromolecular prodrugs (MPDs) of aspirin onto naturally occurring hydrophilic biopolymer pullulan. Pullulan-aspirin conjugates were synthesized by using green carboxylic acid activating reagent 1,1′-carbonyldiimidazole (CDI). The aspirin was first reacted with CDI to prepare aspirin-imidazolide at RT for 24 h which in situ reacted with pre-dissolved pullulan and the reaction preceded further for 24 h at 80 °C under nitrogen....

  5. New Type of Donor-Acceptor Through-Space Conjugated Polymer

    OpenAIRE

    Lin Lin; Yasuhiro Morisaki; Yoshiki Chujo

    2010-01-01

    We report the synthesis and properties of a novel through-space conjugated polymer with a [2.2]paracyclophane skeleton. The obtained polymer possessed donor (fluorene) and acceptor (2,1,3-benzothiadiazole) segments that were alternately π-stacked in proximity via the [2.2]paracyclophane moieties. The good overlap between the emission peak of the donor unit (fluorene) and the CT band of the acceptor unit (2,1,3-benzothiadiazole) caused fluorescence resonance energy transfer, and the visible gr...

  6. New Type of Donor-Acceptor Through-Space Conjugated Polymer

    Directory of Open Access Journals (Sweden)

    Lin Lin

    2010-01-01

    Full Text Available We report the synthesis and properties of a novel through-space conjugated polymer with a [2.2]paracyclophane skeleton. The obtained polymer possessed donor (fluorene and acceptor (2,1,3-benzothiadiazole segments that were alternately π-stacked in proximity via the [2.2]paracyclophane moieties. The good overlap between the emission peak of the donor unit (fluorene and the CT band of the acceptor unit (2,1,3-benzothiadiazole caused fluorescence resonance energy transfer, and the visible green light emission from the acceptor unit was observed.

  7. Albumin–Polymer–Drug Conjugates: Long Circulating, High Payload Drug Delivery Vehicles

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford; Zuwala, Kaja; Pilgram, Oliver

    2016-01-01

    a marginal increase in the circulation lifetime of the drugs. We combine the benefits of the two platforms and at the same time overcome their respective limitations. Specifically, we develop the synthesis of albumin–polymer–drug conjugates to obtain long circulating, high payload drug delivery vehicles......Albumin is an exquisite tool of nature used in biomedicine to achieve long blood residence time for drugs, but the payload it can carry is typically limited to one molecule per protein. In contrast, synthetic macromolecular prodrugs contain multiple copies of drugs per polymer chain but offer only...... the drug in terms of efficacy of treatment...

  8. Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

    Directory of Open Access Journals (Sweden)

    Thibault E. Schmid

    2015-12-01

    Full Text Available The copper-catalyzed asymmetric conjugate addition (ACA of nucleophiles onto polyenic Michael acceptors represents an attractive and powerful methodology for the synthesis of relevant chiral molecules, as it enables in a straightforward manner the sequential generation of two or more stereogenic centers. In the last decade, various chiral copper-based catalysts were evaluated in combination with different nucleophiles and Michael acceptors, and have unambiguously demonstrated their usefulness in the control of the regio- and enantioselectivity of the addition. The aim of this review is to report recent breakthroughs achieved in this challenging field.

  9. Identification of amino acid and glutathione N-conjugates of toosendanin: bioactivation of the furan ring mediated by CYP3A4.

    Science.gov (United States)

    Yu, Jinghua; Deng, Pan; Zhong, Dafang; Chen, Xiaoyan

    2014-09-15

    Toosendanin (TSN) is a hepatotoxic triterpenoid extracted from Melia toosendan Sieb et Zucc. Considering that TSN contains the structural alert of the furan ring, it is believed that bioactivation of TSN may be responsible for its toxicity. Herein, the bioactivation potential and metabolism profiles of TSN were investigated. After an oral administration of 10 mg/kg TSN to rats, esterolysis and conjugation with amino acids were identified as the main metabolic pathways. The same types of conjugates were detected in liver microsomes in an NADPH-dependent manner. According to the remaining amount of the parent drug, the reactivity of trapping reagents with TSN reactive metabolites was sorted in a decreasing order of N(α)-(tert-butoxycarbonyl)-l-lysine (Boc-Lys) > alanine, lysine, taurine, phenylalanine, serine, glutamic acid, glycine, and glutathione (GSH) > cysteine. No conjugates were observed in NADPH and N-acetyl cysteine (NAC)-supplemented human liver microsomal incubations. Further phenotyping studies and the chemical synthesis of the major conjugated standards proved that TSN was bioactivated by CYP3A4 and yielded a cis-butene-1,4-dial intermediate, which was prone to undergo 1,2-addition with the amino group of amino acids and GSH to form 3-pyrroline-2-one adducts. The sulfydryl group of GSH also attacked the intermediate and yielded S-conjugates by 1,4- or 1,2-addition, which would form pyrrole conjugates by further reacting with the amino group. Compared to the well-recognized S-conjugation of the furan ring, N-conjugation with multiple amino acids and GSH played a more important part in the elimination of reactive metabolites of TSN. The significance of these conjugates requires further investigation.

  10. Conjugated Polymers and Oligomers: Structural and Soft Matter Aspects

    DEFF Research Database (Denmark)

    This book identifies modern topics and current trends of structural and soft matter aspects of conjugated polymers and oligomers. Each chapter recognizes an active research line where structural perspective dominates research and therefore the book covers fundamental aspects of persistent...... conjugated polymer backbone, water soluble conjugated polyelectrolytes and surfactants, conjugated molecules and biomolecules and DNA and the advanced use of synchrotron radiation and electron microscopy to find out structural details in conjugated molecule films and devices as well as under ambient...... and extreme conditions....

  11. Convergent synthesis of the right-hand segment of ciguatoxin.

    Science.gov (United States)

    Hamajima, Akinari; Isobe, Minoru

    2006-03-16

    [reaction: see text] A convergent synthesis of the right-hand half of ciguatoxin (the HIJKLM ring system) has been achieved with complete stereocontrol in the introduction of the stereocenters on the eight-membered I ring. Key steps are Sonogashira coupling, dicobalt complexation, intramolecular conjugate addition, and hydrogenation of an endo-olefin to provide the 39-alpha-methyl group.

  12. Synthesis, characterization and ion recognition studies of lower rim ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 125; Issue 6. Synthesis, characterization and ion recognition studies of lower rim 1,3-di{rhodamine} conjugate of calix[4]arene. Jugun Prakash Chinta Jayaraman Dessingou Chebrolu Pulla Rao. Regular Articles Volume 125 Issue 6 November 2013 pp 1455-1461 ...

  13. Solid-phase synthesis of 3-amino-2-pyrazolines

    DEFF Research Database (Denmark)

    Nielsen, John

    1998-01-01

    The development of a solid-phase synthesis of 3-amino-2-pyrazolines is described. Conjugate addition of hydrazines to alpha,beta-unsaturated nitriles followed by cyclization yields 3-amino-2-pyrazolines. Acylation or sulfonation of the free amino-group yields a 24 member library of 3-amino-2...

  14. Solid-phase synthesis of 3-amino-2-pyrazolines

    DEFF Research Database (Denmark)

    Lyngsø, Lars O.; Nielsen, John

    1998-01-01

    The development of a solid-phase synthesis of 3-amino-2-pyrazolines is described. Conjugate addition of hydrazines to α,β-unsaturated nitriles followed by cyclization yields 3-amino-2-pyrazolines. Acylation or sulfonation of the free amino-group yields a 24 member library of 3-amino-2- pyrazolines....

  15. The synthesis of some unsaturated 4-substituted-g-lactones

    OpenAIRE

    SUREN HUSINEC; VLADIMIR SAVIC

    2000-01-01

    The synthesis of conjugated and nonconjugated unsaturated 4-substituted lactones of type 1 and 2 are described. The type 1 lactone was prepared by a two step procedure employing Bredereck's reagent. The type 2 lactone was synthesised by combining the Claisen-Ireland rearrangement and selenolactonisation.

  16. The synthesis of some unsaturated 4-substituted-g-lactones

    Directory of Open Access Journals (Sweden)

    SUREN HUSINEC

    2000-02-01

    Full Text Available The synthesis of conjugated and nonconjugated unsaturated 4-substituted lactones of type 1 and 2 are described. The type 1 lactone was prepared by a two step procedure employing Bredereck's reagent. The type 2 lactone was synthesised by combining the Claisen-Ireland rearrangement and selenolactonisation.

  17. Synthesis of Poly(m-pyridylene-1,2-diphenylvinylene

    Directory of Open Access Journals (Sweden)

    Rosana S. Montani

    2000-03-01

    Full Text Available The synthesis by dehalogenating polycondensation and characterization of a new soluble conjugated polymer, poly(m-pyridylene-1,2-diphenylvinylene, DP-PPyV, is reported here. It shows good mechanical properties and a λmax = 330 nm. The maximum intensity peak of MALDI-TOF corresponds to 1.800 Da.

  18. Solid-Phase Synthesis of PEGylated Lipopeptides Using Click Chemistry

    DEFF Research Database (Denmark)

    Jølck, Rasmus Irming; Berg, Rolf Henrik; Andresen, Thomas Lars

    2010-01-01

    A versatile methodology for efficient synthesis of PEGylated lipopeptides via CuAAC “Click” conjugation between alkyne-bearing solid-supported lipopeptides and azido-functionalized PEGs is described. This new and very robust method offers a unique platform for synthesizing PEGylated lipopeptides...

  19. Diketopyrrolopyrrole-diketopyrrolopyrrole-based conjugated copolymer for high-mobility organic field-effect transistors

    KAUST Repository

    Kanimozhi, Catherine K.

    2012-10-10

    In this communication, we report the synthesis of a novel diketopyrrolopyrrole-diketopyrrolopyrrole (DPP-DPP)-based conjugated copolymer and its application in high-mobility organic field-effect transistors. Copolymerization of DPP with DPP yields a copolymer with exceptional properties such as extended absorption characteristics (up to ∼1100 nm) and field-effect electron mobility values of >1 cm 2 V -1 s -1. The synthesis of this novel DPP-DPP copolymer in combination with the demonstration of transistors with extremely high electron mobility makes this work an important step toward a new family of DPP-DPP copolymers for application in the general area of organic optoelectronics. © 2012 American Chemical Society.

  20. Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability

    Directory of Open Access Journals (Sweden)

    Satu Ikonen

    2011-11-01

    Full Text Available Synthesis, detailed structural characterization (X-ray, NMR, MS, IR, elemental analysis, and studies of toxicity, antioxidant activity and bioavailability of unique potent anti-atherosclerotic succinobucol-steroid conjugates are reported. The conjugates consist of, on one side, the therapeutically important drug succinobucol ([4-{2,6-di-tert-butyl-4-[(1-{[3-tert-butyl-4-hydroxy-5-(propan-2-ylphenyl]sulfanyl}ethylsulfanyl]phenoxy}-4-oxo-butanoic acid] possessing an antioxidant and anti-inflammatory activity, and on the other side, plant stanol/sterols (stigmastanol, β-sitosterol and stigmasterol possessing an ability to lower the blood cholesterol level. A cholesterol-succinobucol prodrug was also prepared in order to enhance the absorption of succinobucol through the intestinal membrane into the organism and to target the drug into the place of lipid metabolism—The enterohepatic circulation system. Their low toxicity towards mice fibroblasts at maximal concentrations, their antioxidant activity, comparable or even higher than that of ascorbic acid as determined by direct quenching of the DPPH radical, and their potential for significantly altering total and LDL cholesterol levels, suggest that these conjugates merit further studies in the treatment of cardiovascular or other related diseases. A brief discussion of succinobucol’s ability to quench the radicals, supported with a computational model of the electrostatic potential mapped on the electron density surface of the drug, is also presented.

  1. Fabrication, characterization, thermal stability and nanoassemblies of novel pullulan-aspirin conjugates

    Directory of Open Access Journals (Sweden)

    Muhammad A. Hussain

    2017-05-01

    Full Text Available Present study deals with homogeneous and one-pot synthesis of novel macromolecular prodrugs (MPDs of aspirin onto naturally occurring hydrophilic biopolymer pullulan. Pullulan-aspirin conjugates were synthesized by using green carboxylic acid activating reagent 1,1′-carbonyldiimidazole (CDI. The aspirin was first reacted with CDI to prepare aspirin-imidazolide at RT for 24 h which in situ reacted with pre-dissolved pullulan and the reaction preceded further for 24 h at 80 °C under nitrogen. Degree of substitution (DS 0.32–0.40 of aspirin onto pullulan was calculated from 1H NMR spectroscopy. Spectroscopic techniques confirmed the high covalent drug loading and purity. Thermal analysis has revealed that new MPDs of aspirin are thermally more stable than pure aspirin. The activation energy, order and frequency factor of the degradation reactions were calculated using Broido, Friedman and Chang models. The amphiphilic pullulan-aspirin conjugates self-assembled in nanoparticles without further structural modifications at solvent interface in the range of 500–680 nm as examined by transmission electron microscopy. These novel pullulan-aspirin conjugates with masked COOH functional group could be potentially safe prodrugs for the stomach.

  2. Influence of aggregated morphology on carbon dioxide uptake of polythiophene conjugated organic networks

    International Nuclear Information System (INIS)

    Qiao, Shanlin; Du, Zhengkun; Huang, Wei; Yang, Renqiang

    2014-01-01

    Two novel thiophene-based conjugated networks CMPs-TTT and CMPs-DTBT were designed and prepared with different steric configuration building blocks by FeCl 3 oxidative coupling polymerization. UV–vis spectra, FE-SEM and TEM images showed CMPs-TTT and CMPs-DTBT having the different aggregated morphologies. After porous analysis and gas adsorption test, the result showed CO 2 uptake capacity of CMPs-DTBT with amorphous aggregation model is 2.88 times and 2.66 times greater than that of CMPs-TTT with large lamellar structure model at 273 K and 298 K (1.0 bar), respectively. As a result, this communication proved that change the topological structure of the polymer can influence the CO 2 adsorption capacity significantly. - Graphical abstract: Two thiophene-based conjugated networks were prepared with different steric configuration building blocks, and they show various CO 2 uptake capacity and sorption isosteric enthalpies, although they have identical chemical constitution. - Highlights: • Topological-directed design and synthesis two conjugated porous polymers. • Two thiophene-based CMPs show different aggregated morphologies. • They exhibit similar porosity structure and different CO 2 uptake capacity

  3. Curdlan-Conjugated PLGA Nanoparticles Possess Macrophage Stimulant Activity and Drug Delivery Capabilities.

    Science.gov (United States)

    Tukulula, Matshawandile; Hayeshi, Rose; Fonteh, Pascaline; Meyer, Debra; Ndamase, Abongile; Madziva, Michael T; Khumalo, Vincent; Labuschagne, Philip; Lubuschagne, Philip; Naicker, Brendon; Swai, Hulda; Dube, Admire

    2015-08-01

    There is significant interest in the application of nanoparticles to deliver immunostimulatory signals to cells. We hypothesized that curdlan (immune stimulating polymer) could be conjugated to PLGA and nanoparticles from this copolymer would possess immunostimulatory activity, be non-cytotoxic and function as an effective sustained drug release system. Carbodiimide chemistry was employed to conjugate curdlan to PLGA. The conjugate (C-PLGA) was characterized using (1)H and (13)C NMR, FTIR, DSC and TGA. Nanoparticles were synthesized using an emulsion-solvent evaporation technique. Immunostimulatory activity was characterized in THP-1 derived macrophages. MTT assay and real-time impedance measurements were used to characterize polymer and nanoparticle toxicity and uptake in macrophages. Drug delivery capability was assessed across Caco-2 cells using rifampicin as a model drug. Spectral characterization confirmed successful synthesis of C-PLGA. C-PLGA nanoparticles enhanced phosphorylated ERK production in macrophages indicating cell stimulation. Nanoparticles provided slow release of rifampicin across Caco-2 cells. Polymers but not nanoparticles altered the adhesion profiles of the macrophages. Impedance measurements suggested Ca(2+) dependent uptake of nanoparticles by the macrophages. PLGA nanoparticles with macrophage stimulating and sustained drug delivery capabilities have been prepared. These nanoparticles can be used to stimulate macrophages and concurrently deliver drug in infectious disease therapy.

  4. Amplified protein detection and identification through DNA-conjugated M13 bacteriophage.

    Science.gov (United States)

    Lee, Ju Hun; Domaille, Dylan W; Cha, Jennifer N

    2012-06-26

    Sensitive protein detection and accurate identification continues to be in great demand for disease screening in clinical and laboratory settings. For these diagnostics to be of clinical value, it is necessary to develop sensors that have high sensitivity but favorable cost-to-benefit ratios. However, many of these sensing platforms are thermally unstable or require significant materials synthesis, engineering, or fabrication. Recently, we demonstrated that naturally occurring M13 bacteriophage can serve as biological scaffolds for engineering protein diagnostics. These viruses have five copies of the pIII protein, which can bind specifically to target antigens, and thousands of pVIII coat proteins, which can be genetically or chemically modified to react with signal-producing materials, such as plasmon-shifting gold nanoparticles (Au NPs). In this report, we show that DNA-conjugated M13 bacteriophage can act as inexpensive protein sensors that can rapidly induce a color change in the presence of a target protein yet also offer the ability to identify the detected antigen in a separate step. Many copies of a specific DNA oligonucleotide were appended to each virus to create phage-DNA conjugates that can hybridize with DNA-conjugated gold nanoparticles. In the case of a colorimetric positive result, the identity of the antigen can also be easily determined by using a DNA microarray. This saves precious resources by establishing a rapid, quantitative method to first screen for the presence of antigen followed by a highly specific typing assay if necessary.

  5. MARITAL ACT AS THE ACT OF THE CONJUGAL KNOWLEDGE WEDNESDAY CATECHESIS OF JOHN PAUL II

    Directory of Open Access Journals (Sweden)

    Jucewicz Antoni

    2017-12-01

    Full Text Available The author of this essay examines a series of short talks on marital act delivered by John Paul II on his Wednesday Catechesis, where the pope described it as the act of the conjugal knowledge. The essay includes the following themes: sexuality in the context of the original sin; marital union of persons as knowledge; parenthood as the sense of knowledge; motherhood in the perspective of knowledge; knowledge-labour in the eschatological perspective. Marital act implies a mutual gift of the whole person. Conjugal union between man and woman reveals the sense of their bodies as those of the husband and the wife. Mutual, unconditional and irrevocable acceptance echoes, as it were, the loving act of God towards them. God loves man for his own sake. Communion between spouses stimulates their deep mutual affirmation. Marital love, realised in the marital act, is the act of procreation. Marital relationship gives rise to the reality of another person. Conjugal knowledge leads to the unveiling of the mystery of another person, the fruit of the love between the spouses. The child appears as a kind of the synthesis of their love, and the shared image of the spouses. God reveals His creative power in the marital act of love and conception, and then extends it far beyond the horizons of death. The innermost sense of childbirth lies in the opening up to the life-giving power of God. In that, it demonstrates the Paschal tenacity of life.

  6. A Review of Therapeutic Aptamer Conjugates with Emphasis on New Approaches

    Directory of Open Access Journals (Sweden)

    John G. Bruno

    2013-03-01

    Full Text Available The potential to emulate or enhance antibodies with nucleic acid aptamers while lowering costs has prompted development of new aptamer-protein, siRNA, drug, and nanoparticle conjugates. Specific focal points of this review discuss DNA aptamers covalently bound at their 3' ends to various proteins for enhanced stability and greater pharmacokinetic lifetimes in vivo. The proteins can include Fc tails of IgG for opsonization, and the first component of complement (C1q to trigger complement-mediated lysis of antibiotic-resistant Gram negative bacteria, cancer cells and possibly some parasites during vulnerable stages. In addition, the 3' protein adduct may be a biotoxin, enzyme, or may simply be human serum albumin (HSA or a drug known to bind HSA, thereby retarding kidney and other organ clearance and inhibiting serum exonucleases. In this review, the author summarizes existing therapeutic aptamer conjugate categories and describes his patented concept for PCR-based amplification of double-stranded aptamers followed by covalent attachment of proteins or other agents to the chemically vulnerable overhanging 3' adenine added by Taq polymerase. PCR amplification of aptamers could dramatically lower the current $2,000/gram cost of parallel chemical oligonucleotide synthesis, thereby enabling mass production of aptamer-3'-protein or drug conjugates to better compete against expensive humanized monoclonal antibodies.

  7. General classes of double phase conjugation.

    Science.gov (United States)

    Sternklar, S

    1995-02-01

    The double phase-conjugate mirror (DPCM) is a stimulated four-wave mixing effect, mediated by either a chi(3) mechanism or a photorefractive effect. The type of grating that operates in the DPCM can be a transmission or reflection grating, depending on the wave-mixing configuration. Any combination of nonlinearity and grating geometry is possible, so that four general DPCM classes emerge. An analytic solution of the last unsolved class, the photorefractive reflection DPCM, is presented. With these results, general observations concerning the four categories of double phase conjugation are made. An important conclusion is that the type of grating geometry and its associated boundary conditions dictate many of the basic features of the DPCM, regardless of the nonlinearity involved.

  8. Stochastic Spectral and Conjugate Descent Methods

    KAUST Repository

    Kovalev, Dmitry

    2018-02-11

    The state-of-the-art methods for solving optimization problems in big dimensions are variants of randomized coordinate descent (RCD). In this paper we introduce a fundamentally new type of acceleration strategy for RCD based on the augmentation of the set of coordinate directions by a few spectral or conjugate directions. As we increase the number of extra directions to be sampled from, the rate of the method improves, and interpolates between the linear rate of RCD and a linear rate independent of the condition number. We develop and analyze also inexact variants of these methods where the spectral and conjugate directions are allowed to be approximate only. We motivate the above development by proving several negative results which highlight the limitations of RCD with importance sampling.

  9. Antibody conjugate radioimmunotherapy of superficial bladder cancer

    International Nuclear Information System (INIS)

    Perkins, Alan; Hopper, Melanie; Murray, Andrea; Frier, Malcolm; Bishop, Mike

    2002-01-01

    The administration of antibody conjugates for cancer therapy is now proving to be of clinical value. We are currently undertaking a programme of clinical studies using the monoclonal antibody C 595 (gG3) which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radio immuno conjugates of the C 595 antibody have been produced with high radiolabelling efficiency and immuno reactivity using Tc-99 m and In-111 for diagnostic imaging, and disease staging and the cytotoxic radionuclides Cu-67 and Re-188 for therapy of superficial bladder cancer. A Phase I/II therapeutic trail involving the intravesical administration of antibody directly into the bladder has now begun. (author)

  10. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.

    Science.gov (United States)

    Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo

    2015-09-01

    Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition.

  11. Towards an integrated model of bacterial conjugation.

    Science.gov (United States)

    Cabezón, Elena; Ripoll-Rozada, Jorge; Peña, Alejandro; de la Cruz, Fernando; Arechaga, Ignacio

    2015-01-01

    Bacterial conjugation is one of the main mechanisms for horizontal gene transfer. It constitutes a key element in the dissemination of antibiotic resistance and virulence genes to human pathogenic bacteria. DNA transfer is mediated by a membrane-associated macromolecular machinery called Type IV secretion system (T4SS). T4SSs are involved not only in bacterial conjugation but also in the transport of virulence factors by pathogenic bacteria. Thus, the search for specific inhibitors of different T4SS components opens a novel approach to restrict plasmid dissemination. This review highlights recent biochemical and structural findings that shed new light on the molecular mechanisms of DNA and protein transport by T4SS. Based on these data, a model for pilus biogenesis and substrate transfer in conjugative systems is proposed. This model provides a renewed view of the mechanism that might help to envisage new strategies to curb the threating expansion of antibiotic resistance. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  12. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita

    2011-11-01

    Full Text Available Conjugated fatty acids (CFA have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1% in natural products, conjugated linolenic acids (CLN are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid. Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.

  13. Conjugation, characterization and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis.

    Science.gov (United States)

    Topuzogullari, Murat; Cakir Koc, Rabia; Dincer Isoglu, Sevil; Bagirova, Melahat; Akdeste, Zeynep; Elcicek, Serhat; Oztel, Olga N; Yesilkir Baydar, Serap; Canim Ates, Sezen; Allahverdiyev, Adil M

    2013-06-03

    Research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character in comparison to classical adjuvants. For example, polyacrylic acid (PAA) is a weak polyelectrolyte and has been used in several biomedical applications such as immunological studies, drug delivery, and enzyme immobilization. However, to our knowledge, there are no studies that document immune-stimulant properties of PAA in Leishmania infection. Therefore, we aimed to develop a potential vaccine candidate against leishmaniasis by covalently conjugating PAA with an immunologically vital molecule of lipophosphoglycan (LPG) found in Leishmania parasites. In the study, LPG and PAA were conjugated by a multi-step procedure, and final products were analyzed with GPC and MALDI-TOF MS techniques. In cytotoxicity experiments, LPG-PAA conjugates did not indicate toxic effects on L929 and J774 murine macrophage cells. We assume that LPG-PAA conjugate can be a potential vaccine candidate, and will be immunologically characterized in further studies to prove its potential.

  14. Novel Design Strategies for Platinum-Containing Conjugated Polymers and Small Molecules for Organic Solar Cells

    Science.gov (United States)

    He, Wenhan

    Current state-of-the-art organic solar cells (OSCs) adopt the strategy of using conjugated polymers or small molecules as donors and fullerene derivatives as acceptors in their active layers. Regarding to the donors of interest, the conjugated polymers and small molecules coupled with heavy metals have been less explored compared to their counterparts. Among various transition metal complexes applied, Pt(II) complexes are unique because of their intrinsic square planar geometries and ability to serve as building blocks for conjugated systems. Furthermore, the heavy metal Pt facilitates the formation of triplet excitons with longer life times through spin-orbital coupling which are of benefit for the OSCs application. However, in order to obtain low bandgap polymers, people are intended to use chromophores with long conjugated length, nevertheless such design will inevitably dilute the spin-orbital coupling effect and finally influence the formation of triplet excitons. Furthermore, the majority of Pt-containing conjugated systems reported so far shared a common feature-- they all possessed "dumbbell" shaped structures and were amorphous, leading to poor device performance. In addition, there were few examples reporting the capture of the triplet excitons by the fullerene acceptors in the OSCs since there is a mismatch between the triplet energy state (T1) of the Pt-containing compounds and the LUMO level of fullerene acceptors. As a result, these three intrinsic problems will impede the further development of such a field. In order to solve these problems, I originally designed and synthesized three novel compounds with unique proprieties named as Bodipy-Pt, Pt-SM and C60+SDS-. Specifically, Bodipy has the advantages of compact size, easy to synthesis and high fluorescence quantum yield which can effectively solve the problem of long conjugated length. While in terms of second problem, the new Pt-SM possessed a "roller-wheel" structural design with increased

  15. A water-soluble conjugated polymer for protein identification and denaturation detection.

    Science.gov (United States)

    Xu, Qingling; Wu, Chunxian; Zhu, Chunlei; Duan, Xinrui; Liu, Libing; Han, Yuchun; Wang, Yilin; Wang, Shu

    2010-12-03

    Rapid and sensitive methods to detect proteins and protein denaturation have become increasingly needful in the field of proteomics, medical diagnostics, and biology. In this paper, we have reported the synthesis of a new cationic water-soluble conjugated polymer that contains fluorene and diene moieties in the backbone (PFDE) for protein identification by sensing an array of PFDE solutions in different ionic strengths using the linear discriminant analysis technique (LDA). The PFDE can form complexes with proteins by electrostatic and/or hydrophobic interactions and exhibits different fluorescence response. Three main factors contribute to the fluorescence response of PFDE, namely, the net charge density on the protein surface, the hydrophobic nature of the protein, and the metalloprotein characteristics. The denaturation of proteins can also be detected using PFDE as a fluorescent probe. The interactions between PFDE and proteins were also studied by dynamic light scattering (DLS) and isothermal titration microcalorimetry (ITC) techniques. In contrast to other methods based on conjugated polymers, the synthesis of a series of quencher or dye-labeled acceptors or protein substrates has been avoided in our method, which significantly reduces the cost and the synthetic complexity. Our method provides promising applications on protein identification and denaturation detection in a simple, fast, and label-free manner based on non-specific interaction-induced perturbation of PFDE fluorescence response.

  16. Design, synthesis, and evaluation of 2-diethanolamino-4,8-diheptamethyleneimino-2-(N-aminoethyl-N-ethanolamino)-6-(N,N-diethanolamino)pyrimido[5,4-d]pyrimidine-fluorescein conjugate (8MDP-fluor), as a novel equilibrative nucleoside transporter probe.

    Science.gov (United States)

    Lin, Wenwei; Buolamwini, John K

    2011-06-15

    Nucleoside transporters are integral membrane glycoproteins that play critical roles in physiological nucleoside and nucleobase fluxes, and influence the efficacy of many nucleoside chemotherapy drugs. Fluorescent reporter ligands/substrates have been shown to be useful in the analysis of nucleoside transporter (NT) protein expression and discovery of new NT inhibitors. In this study, we have developed a novel dipyridamole (DP)-based equilibrative nucleoside transporter 1 (ENT1) fluorescent probe. The potent ENT1 and ENT2 inhibitor analogue of dipyridamole, 2,6-bis(diethanolamino)-4,8-diheptamethyleneiminopyrimido[5,4-d]pyrimidine (4, 8MDP), was modified to replace one β-hydroxyethyl group of the amino substituent at the 2-position with a β-aminoethyl group and then conjugated through the amino group to 6-(fluorescein-5-carboxamido)hexanoyl moiety to obtain a new fluorescent molecule, 2-diethanolamino-4,8-diheptamethyleneimino-2-(N-aminoethyl-N-ethanolamino)-6-(N,N-diethanolamino)pyrimido[5,4-d]pyrimidine-fluorescein conjugate, designated 8MDP-fluorescein (8MDP-fluor, 6). The binding affinities of 8MDP-fluor at ENT1 and ENT2 are reflected by the uridine uptake inhibitory K(i) values of 52.1 nM and 285 nM, respectively. 8MDP-fluor was successfully demonstrated to be a flow cytometric probe for ENT1 comparable to the nitrobenzylmercaptopurine riboside (NBMPR) analogue ENT1 fluorescent probe SAENTA-X8-fluorescein (SAENTA-fluor, 1). This is the first reported dipyridamole-based ENT1 fluorescent probe, which adds a novel tool for probing ENT1, and possibly ENT2.

  17. Co-conjugation vis-à-vis individual conjugation of α-amylase and glucoamylase for hydrolysis of starch.

    Science.gov (United States)

    Jadhav, Swati B; Singhal, Rekha S

    2013-10-15

    Two enzymes, α-amylase and glucoamylase have been individually and co-conjugated to pectin by covalent binding. Both the enzyme systems showed better thermal and pH stability over the free enzyme system with the complete retention of original activities. Mixture of individually conjugated enzymes showed lower inactivation rate constant with longer half life than the co-conjugated enzyme system. Individually conjugated enzymes showed an increase of 56.48 kJ/mole and 38.22 kJ/mole in activation energy for denaturation than the free enzymes and co-conjugated enzymes, respectively. Km as well as Vmax of individually and co-conjugated enzymes was found to be higher than the free enzymes. SDS-polyacrylamide gel electrophoresis confirmed the formation of conjugate and co-conjugate as evident by increased molecular weight. Both the enzyme systems were used for starch hydrolysis where individually conjugated enzymes showed highest release of glucose at 60 °C and pH 5.0 as compared to free and co-conjugated enzyme. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Improved synthesis of (S)-N-Boc-5-oxaproline for protein synthesis with the α-ketoacid-hydroxylamine (KAHA) ligation.

    Science.gov (United States)

    Murar, Claudia E; Harmand, Thibault J; Bode, Jeffrey W

    2017-09-15

    We describe a new route for the synthesis of (S)-N-Boc-5-oxaproline. This building block is a key element for the chemical synthesis of proteins with the α-ketoacid-hydroxylamine (KAHA) ligation. The new synthetic pathway to the enantiopure oxaproline is based on a chiral amine mediated enantioselective conjugate addition of a hydroxylamine to trans-4-oxo-2-butenoate. This route is practical, scalable and economical and provides decagram amounts of material for protein synthesis and conversion to other protected forms of (S)-oxaproline. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Docosahexaenoic Acid Conjugation Enhances Distribution and Safety of siRNA upon Local Administration in Mouse Brain

    Directory of Open Access Journals (Sweden)

    Mehran Nikan

    2016-01-01

    Full Text Available The use of siRNA-based therapies for the treatment of neurodegenerative disease requires efficient, nontoxic distribution to the affected brain parenchyma, notably the striatum and cortex. Here, we describe the synthesis and activity of a fully chemically modified siRNA that is directly conjugated to docosahexaenoic acid (DHA, the most abundant polyunsaturated fatty acid in the mammalian brain. DHA conjugation enables enhanced siRNA retention throughout both the ipsilateral striatum and cortex following a single, intrastriatal injection (ranging from 6–60 μg. Within these tissues, DHA conjugation promotes internalization by both neurons and astrocytes. We demonstrate efficient and specific silencing of Huntingtin mRNA expression in both the ipsilateral striatum (up to 73% and cortex (up to 51% after 1 week. Moreover, following a bilateral intrastriatal injection (60 μg, we achieve up to 80% silencing of a secondary target, Cyclophilin B, at both the mRNA and protein level. Importantly, DHA-hsiRNAs do not induce neural cell death or measurable innate immune activation following administration of concentrations over 20 times above the efficacious dose. Thus, DHA conjugation is a novel strategy for improving siRNA activity in mouse brain, with potential to act as a new therapeutic platform for the treatment of neurodegenerative disorders.

  20. Mobilizable Rolling-Circle Replicating Plasmids from Gram-Positive Bacteria: A Low-Cost Conjugative Transfer

    Science.gov (United States)

    Fernández-López, Cris; Bravo, Alicia; Ruiz-Cruz, Sofía; Solano-Collado, Virtu; Garsin, Danielle A.; Lorenzo-Díaz, Fabián; Espinosa, Manuel

    2014-01-01

    Chapter summary Conjugation is a key mechanism for horizontal gene transfer in bacteria. Some plasmids are not self-transmissible but can be mobilized by functions encoded in trans provided by other auxiliary conjugative elements. Although the transfer efficiency of mobilizable plasmids is usually lower than that of conjugative elements, mobilizable plasmidsare more frequently found in nature. In this sense, replication and mobilization can be considered as important mechanisms influencing plasmid promiscuity. Here we review the present available information on two families of small mobilizable plasmids from Gram-positive bacteria that replicate via the rolling-circle mechanism. One of these families, represented by the streptococcal plasmid pMV158, is an interesting model since it contains a specific mobilization module (MOBV) that is widely distributed among mobilizable plasmids. We discuss a mechanism in which the promiscuity of the pMV158 replicon is based on the presence of two origins of lagging strand synthesis. The current strategies to assess plasmid transfer efficiency as well as to inhibit conjugative plasmid transfer are presented. Some applications of these plasmids as biotechnological tools are also reviewed. PMID:25606350

  1. Conjugated Polymer based sensor for detecting explosives such as RDX (1,3,5-Trinitroperhydro-1,3,5-triazine)

    Science.gov (United States)

    Kumar, Abhishek; Anandkathir, Robinson; Kumar, Jayant

    2009-03-01

    Conjugated polymers are an important class of materials and have attracted great scientific interests because of their unique optical and electrical properties. Synthesis of various conjugated polymers has been reported for detecting DNT and TNT. Here, for the first time, we report the synthesis and characterization of a conjugated polymer based on thiophene, Poly[2-(3-thienyl)ethanol n-butoxycarbonylmethylurethane] (PURET), for the detection of RDX via fluorescence quenching. The incorporation of judiciously chosen bulky butoxycarbonylmethyl urethane side group in the back bone of polythiophene reduces the aggregation, improves the solubility of the polymer in the organic solvents and quantum yield of fluorescence. We have observed a 15 % decrease of fluorescence in 60 sec in thin films of PURET exposed to the saturated vapor of RDX at room temperature. The large exciton diffusion length and interaction between side group and the quencher molecule are believed to be the reasons for enhanced RDX detection. Sensitivity below 5 parts per trillion (ppt) has been demonstrated for RDX at room temperature. The effect of nanostructures (electrospun nanofibers and stamped 1 D periodic pattern) on sensitivity and response time will also be discussed.

  2. Synthesis and Studies of Sulfur-Containing Heterocyclic Molecules for Molecular Electronics

    DEFF Research Database (Denmark)

    Mazzanti, Virginia

    This work describes the synthesis and studies of sulfur containing π conjugated heterocycles, which are considered interesting motifs in the field of molecular electronics. The first project, which is covered in Chapter 1, concerns the functionalization of tetracycle dibenzo[bc,fg][1,4]dithiapent......This work describes the synthesis and studies of sulfur containing π conjugated heterocycles, which are considered interesting motifs in the field of molecular electronics. The first project, which is covered in Chapter 1, concerns the functionalization of tetracycle dibenzo[bc,fg][1...... the synthesis of dimeric structures of redox active system tetrathiafulvalene (TTF). Molecules with different conjugation pathways bridging two TTFs were synthesized and studied using CV and DPV in order to probe the electronic interaction between these two redox units. The last aspect of this thesis, which...

  3. Reflection and transmission of twisted light at phase conjugating interfaces.

    Science.gov (United States)

    Thakur, Anita; Berakdar, Jamal

    2012-01-16

    We study the transmission and the reflection of light beams carrying orbital angular momentum through a dielectric multilayer structure containing phase-conjugating interfaces. We show analytically and demonstrate numerically that the phase conjugation at the interfaces results in a characteristic angular and radial pattern of the reflected beam, a fact that can be exploited for the detection and the characterization of phase conjugation in composite optical materials.

  4. Evolution of conjugation and type IV secretion systems.

    Science.gov (United States)

    Guglielmini, Julien; de la Cruz, Fernando; Rocha, Eduardo P C

    2013-02-01

    Genetic exchange by conjugation is responsible for the spread of resistance, virulence, and social traits among prokaryotes. Recent works unraveled the functioning of the underlying type IV secretion systems (T4SS) and its distribution and recruitment for other biological processes (exaptation), notably pathogenesis. We analyzed the phylogeny of key conjugation proteins to infer the evolutionary history of conjugation and T4SS. We show that single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) conjugation, while both based on a key AAA(+) ATPase, diverged before the last common ancestor of bacteria. The two key ATPases of ssDNA conjugation are monophyletic, having diverged at an early stage from dsDNA translocases. Our data suggest that ssDNA conjugation arose first in diderm bacteria, possibly Proteobacteria, and then spread to other bacterial phyla, including bacterial monoderms and Archaea. Identifiable T4SS fall within the eight monophyletic groups, determined by both taxonomy and structure of the cell envelope. Transfer to monoderms might have occurred only once, but followed diverse adaptive paths. Remarkably, some Firmicutes developed a new conjugation system based on an atypical relaxase and an ATPase derived from a dsDNA translocase. The observed evolutionary rates and patterns of presence/absence of specific T4SS proteins show that conjugation systems are often and independently exapted for other functions. This work brings a natural basis for the classification of all kinds of conjugative systems, thus tackling a problem that is growing as fast as genomic databases. Our analysis provides the first global picture of the evolution of conjugation and shows how a self-transferrable complex multiprotein system has adapted to different taxa and often been recruited by the host. As conjugation systems became specific to certain clades and cell envelopes, they may have biased the rate and direction of gene transfer by conjugation within prokaryotes.

  5. Genetic drift suppresses bacterial conjugation in spatially structured populations

    OpenAIRE

    Freese, Peter D.; Korolev, Kirill S.; Jimenez, Jose I.; Chen, Irene A.

    2014-01-01

    Conjugation is the primary mechanism of horizontal gene transfer that spreads antibiotic resistance among bacteria. Although conjugation normally occurs in surface-associated growth (e.g., biofilms), it has been traditionally studied in well-mixed liquid cultures lacking spatial structure, which is known to affect many evolutionary and ecological processes. Here we visualize spatial patterns of gene transfer mediated by F plasmid conjugation in a colony of Escherichia coli growing on solid ag...

  6. Magnetic Field Effect in Conjugated Molecules-Based Devices

    Science.gov (United States)

    2017-10-23

    AFRL-AFOSR-JP-TR-2017-0073 Magnetic field effect in conjugated molecules-based devices Tzung-Fang Guo NATIONAL CHENG KUNG UNIVERSITY Final Report 10...Final 3. DATES COVERED (From - To) 22 Jul 2014 to 21 Jul 2017 4. TITLE AND SUBTITLE Magnetic field effect in conjugated molecules-based devices 5a... Magnetic field effect in conjugated molecule-based devices. The final year of the project had a collaboration with Professor Bin Hu at the University

  7. Effect of Fatty Acid Conjugation on Antimicrobial Peptide Activity

    National Research Council Canada - National Science Library

    Chu-Kung, Alexander F; Bozzelli, Kristen N; Nguyen, Rose; Tirrell, Matthew V

    2004-01-01

    ... or the conjugate of the nonamphipathic peptide, KAK. The induction of helicity corresponds to a significant improvement in antimicrobial activity as measured by a minimum bactericidal concentration test...

  8. Sources and Bioactive Properties of Conjugated Dietary Fatty Acids.

    Science.gov (United States)

    Hennessy, Alan A; Ross, Paul R; Fitzgerald, Gerald F; Stanton, Catherine

    2016-04-01

    The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.

  9. Homens e violência conjugal: uma análise de estudos brasileiros Men and conjugal violence: an analysis of Brazilian studies

    Directory of Open Access Journals (Sweden)

    Kátia Lenz Cesar de Oliveira

    2011-05-01

    Full Text Available O estudo analisou qualitativamente 54 textos brasileiros sobre homens e violência conjugal, relacionados a atividades de pesquisa ou de intervenção. Primeiramente caracterizou-se o material quanto aos temas abordados, ao foco principal e ao tipo de texto. A seguir fizeram-se sínteses e análises das principais considerações dos textos a partir dos eixos temáticos encontrados: diferentes inteligibilidades da problemática, magnitude da violência conjugal, sentidos de homens relacionados à violência e intervenções e/ou políticas junto a homens agressores. A análise teve como parâmetro o ramo de discussões nacionais e internacionais que se esforça por ultrapassar a polêmica em torno da definição do problema como "violência de gênero" ou "violência conjugal", cunhando sobretudo o pressuposto de que existem diversos estilos de conjugalidade violenta. Concluiu-se que a maior unanimidade dos estudos é pensar a problemática como questão relacional de gênero. Defendeu-se, por fim, a ideia de que a escolha da melhor abordagem articuladora entre os polos da polêmica ainda demanda mais investigações, com metodologias qualitativas junto a atores de diferentes camadas e grupos sociais. Quanto às intervenções, propõem-se investimentos no maior número possível de alternativas, valorizando a singularidade dos casos.This study consisted of a qualitative analysis of 54 Brazilian texts about men and conjugal violence related to research or intervention activities. Initially, the material was divided up according to the topics under scrutiny, the main focus and the type of text. Analysis and synthesis of the main considerations of the texts, based on the thematic points revealed, was then carried out. This included the different approaches to the problem, the magnitude of conjugal violence, the attitudes of men vis-à-vis violence and interventions and/or policies towards male aggressors. The parameter for the analysis was the

  10. Interplay of alternative conjugated pathways and steric interactions on the electronic and optical properties of donor-acceptor conjugated polymers

    KAUST Repository

    Lima, Igo T.

    2014-01-01

    Donor-acceptor π-conjugated copolymers are of interest for a wide range of electronic applications, including field-effect transistors and solar cells. Here, we present a density functional theory (DFT) study of the impact of varying the conjugation pathway on the geometric, electronic, and optical properties of donor-acceptor systems. We consider both linear ("in series"), traditional conjugation among the donor-acceptor moieties versus structures where the acceptor units are appended orthogonally to the linear, donor-only conjugated backbone. Long-range-corrected hybrid functionals are used in the investigation with the values of the tuned long-range separation parameters providing an estimate of the extent of conjugation as a function of the oligomer architecture. Considerable differences in the electronic and optical properties are determined as a function of the nature of the conjugation pathway, features that should be taken into account in the design of donor-acceptor copolymers.

  11. Multicellular computing using conjugation for wiring.

    Science.gov (United States)

    Goñi-Moreno, Angel; Amos, Martyn; de la Cruz, Fernando

    2013-01-01

    Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal "re-programming" and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a "computation" is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the "wiring" between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular computing

  12. Multicellular Computing Using Conjugation for Wiring

    Science.gov (United States)

    Goñi-Moreno, Angel; Amos, Martyn; de la Cruz, Fernando

    2013-01-01

    Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal “re-programming” and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a “computation” is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the “wiring” between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular

  13. Polar reactions of acyclic conjugated bisallenes

    Directory of Open Access Journals (Sweden)

    Reiner Stamm

    2013-01-01

    Full Text Available The chemical behaviour of various alkyl-substituted, acyclic conjugated bisallenes in reactions involving polar intermediates and/or transition states has been investigated on a broad scale for the first time. The reactions studied include lithiation, reaction of the thus formed organolithium salts with various electrophiles (among others, allyl bromide, DMF and acetone, oxidation to cyclopentenones and epoxides, hydrohalogenation (HCl, HBr addition, halogenation (Br2 and I2 addition, and [2 + 2] cycloaddition with chlorosulfonyl isocyanate. The resulting adducts were fully characterized by spectroscopic and analytical methods; they constitute interesting substrates for further organic transformations.

  14. Modeling Transformation and Conjugation in Bacteria Populations

    Science.gov (United States)

    Russo, John; Dong, J. J.

    The rise of antibiotic resistance in bacteria populations is a growing threat to medical treatment of diseases. Transformation, where a cell absorbs a plasmid from its environment, and conjugation, direct transfer of a plasmid from one cell to another, are the two main mechanisms of emergence of antibiotic resistance. We model the processes using a combined approach of Kinetic Monte Carlo simulation and differential equations to describe the plasmid-carrying and plasmid-free populations. Through analysis of our results, we characterize the conditions that lead to dominance of the antibiotic resistant population. NSF-DMR #1248387.

  15. HPMA copolymer conjugates for dual therapy

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Krakovičová, Hana; Šírová, Milada; Říhová, Blanka; Ulbrich, Karel

    2008-01-01

    Roč. 132, č. 3 (2008), s. 63-65 ISSN 0168-3659. [European Symposium on Controlled Drug Delivery /10./. Noordwijk an Zee, 02.04.2008-04.04.2008] R&D Projects: GA MŠk 1M0505; GA AV ČR IAA400500806 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Keywords : dual therapy * polymer conjugates * controlled release Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.690, year: 2008

  16. Rhenium 188 labelling of peptide conjugates

    International Nuclear Information System (INIS)

    Melendez-Alafort, Laura

    2001-01-01

    Many human tumours express high levels, of somatostatin receptors. In order to make possible a radiotherapeutic treatment of this kind for tumour a series of somatostatin analogues that can tightly chelate beta emitting isotopes have been developed in recent years. The work carried out for this thesis has been aimed towards development of a new therapeutic radiopharmaceutical for treatment of somatostatin receptor positive tumours. The first chapters describe work with technetium-99m to establish the labelling and analytical conditions for a somatostatin analogue, [Tyr 3 ]-octreotide (TOC), as a precursor to undertaking labelling studies with the beta emitter rhenium-188. 6-Hydrazinopyridine-3-carboxylic acid (HYNIC) was conjugated to TOC and labelled with 99m using different coligands. Then the stability, receptor binding and biodistribution of each complex were assessed. 99m Tc-HYNIC-TOC using EDDA as coligand showed the best characteristics, and was superior for tumour imaging in humans than the commercially available 111 In-DTPA-octreotide. The conditions for labelling the HYNIC-TOC conjugate with 188 Re were then optimised using tricine as a co-ligand. A labelling yield of ∼80% was achieved. After purification however, the stability of the complex was low. The use of other coligand systems which had proved useful for 99m Tc labelling was explored, but yields were very poor. Other chelators such as diethylenetriamine pentaacetic acid (DTPA), dimercaptosuccinic acid (DMSA) and mercaptoacetyltriglycine (MAG 3 ) were studied as potential co-ligand agents to label the HYNIC-TOC conjugate with 188 Re but, again low yields of the labelled peptide complexes were achieved. A novel 188 Re-HYNIC complex was prepared in high yields using N-N-disubstituted dithiocarbamates as coligands. However to date, the specific activities achieved with this system are relatively low. The use of the [ 99m Tc(CO) 3 (H 2 O) 3 ] complex to label the HYNIC-TOC conjugate was investigated

  17. Evaluation of Haemophilus influenzae Type B Conjugate Vaccine (Meningococcal Protein Conjugate in Canadian Infants

    Directory of Open Access Journals (Sweden)

    David W Scheifele

    1994-01-01

    Full Text Available Objective: To assess adverse effects and immune responses with a three-dose series of Haemophilus influenzae type b meningococcal protein conjugate (PedvaxHIB or Hib.OMP vaccine, including any immunological response alterations from concurrent administration with routine vaccines for infants.

  18. Surface and Electrical Characterization of Conjugated Molecular Wires

    Science.gov (United States)

    Demissie, Abel Tesfahun

    This thesis describes the surface and electrical characterization of ultrathin organic films and interfaces. These films were synthesized on the surface of gold by utilizing layer by layer synthesis via imine condensation. Film growth by imine click (condensation) chemistry is particularly useful for molecular electronics experiments because it provides a convenient means to obtain and extend ?-conjugation in the growth direction. However, in the context of film growth from a solid substrate, the reaction yield per step has not been characterized previously, though it is critically important. To address these issues, my research focused on a comprehensive characterization of oligophenyleneimine (OPI) wires via Rutherford backscattering spectrometry (RBS), X-ray photoelectron spectroscopy (XPS), spectroscopic ellipsometry (SE), reflection-absorption infrared spectroscopy (RAIRS), and cyclic voltammetry (CV). In addition, we had the unique opportunity of developing the first of its kind implementation of nuclear reaction analysis (NRA) to probe the intensity of carbon atoms after each addition step. Overall the combination of various techniques indicated that film growth proceeds in a quantitative manner. Furthermore, the NRA experiment was optimized to measure the carbon content in self-assembled monolayers of alkyl thiols. The results indicated well-resolved coverage values for ultrathin films with consecutive steps of 2 carbon atoms per molecule. Another fundamental problem in molecular electronics is the vast discrepancy in the values of measured resistance per molecule between small and large area molecular junctions. In collaboration with researchers at the National University of Singapore, we addressed these issues by comparing the electrical properties of OPI wires with the eutectic gallium indium alloy (EGaIn) junction (1000 mum2), and conducting probe atomic force microscopy (CP-AFM) junction (50 nm2). Our results showed that intensive (i.e., area

  19. Multi-hop conjugation based bacteria nanonetworks.

    Science.gov (United States)

    Balasubramaniam, Sasitharan; Lio', Pietro

    2013-03-01

    Molecular communication is a new paradigm for nanomachines to exchange information, by utilizing biological mechanism and/or components to transfer information (e.g., molecular diffusion, neuronal networks, molecular motors). One possible approach for molecular communication is through the use of bacteria, which can act as carriers for DNA-based information, i.e., plasmids. This paper analyzes multi-hop molecular nanonetworks that utilize bacteria as a carrier. The proposed approach combines different properties of bacteria to enable multi-hop transmission, such as conjugation and chemotaxis-based motility. Various analyses have been performed, including the correlation between the success rate of plasmid delivery to the destination node, and the role of conjugation in enabling this; as well as analyses on the impact of large topology shapes (e.g., Grid, Random, and Scale-free) on the success rate of plasmid delivery for multiple source-destination nanonetworks. A further solution proposed in this paper is the application of antibiotics to act as filters on illegitimate messages that could be delivered by the bacteria. Our evaluation, which has been conducted through a series of simulations, has shown that numerous bacteria properties fit to properties required for communication networking (e.g., packet filtering, routing, addressing).

  20. Antibody-Conjugated Nanoparticles for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Manuel Arruebo

    2009-01-01

    Full Text Available Nanoscience and Nanotechnology have found their way into the fields of Biotechnology and Medicine. Nanoparticles by themselves offer specific physicochemical properties that they do not exhibit in bulk form, where materials show constant physical properties regardless of size. Antibodies are nanosize biological products that are part of the specific immune system. In addition to their own properties as pathogens or toxin neutralizers, as well as in the recruitment of immune elements (complement, improving phagocytosis, cytotoxicity antibody dependent by natural killer cells, etc., they could carry several elements (toxins, drugs, fluorochroms, or even nanoparticles, etc. and be used in several diagnostic procedures, or even in therapy to destroy a specific target. The conjugation of antibodies to nanoparticles can generate a product that combines the properties of both. For example, they can combine the small size of nanoparticles and their special thermal, imaging, drug carrier, or magnetic characteristics with the abilities of antibodies, such as specific and selective recognition. The hybrid product will show versatility and specificity. In this review, we analyse both antibodies and nanoparticles, focusing especially on the recent developments for antibody-conjugated nanoparticles, offering the researcher an overview of the different applications and possibilities of these hybrid carriers.

  1. Organic synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, S.E.

    1991-01-01

    This paper reports on reactions of organoboranes. Organoboron routes to unsaturated hydrocarbons. Boronic ester homologation. Properties of organosilicon compounds. Alkene synthesis (Peterson olefination). Allylsilanes and acylsilanes.

  2. Chemosensitizing indomethacin-conjugated chitosan oligosaccharide nanoparticles for tumor-targeted drug delivery.

    Science.gov (United States)

    Lee, Jae-Young; Termsarasab, Ubonvan; Lee, Mee Yeon; Kim, Dong-Hwan; Lee, Song Yi; Kim, Jung Sun; Cho, Hyun-Jong; Kim, Dae-Duk

    2017-07-15

    A chitosan oligosaccharide (CSO)-indomethacin (IDM) conjugate (CI) was synthesized to fabricate chemosensitizing nanoparticles (NPs) for tumor-targeted drug delivery. IDM was conjugated to a CSO backbone via amide bond formation, of which successful synthesis was confirmed by proton-nuclear magnetic resonance analyses. Doxorubicin (DOX)-loaded CI (CI10/DOX; CI:DOX=10:1 [w/w]) NPs with IDM increased in the presence of A549 cell lysates. In A549 cells (human lung carcinoma cells), more efficient cellular uptake of CI10/DOX NPs than that of free DOX was observed by using confocal laser scanning microscopy and flow cytometry. The in vitro cytotoxicity of CI10/DOX NPs in A549 cells was higher than those of free DOX and CI NPs with free DOX groups. In vivo pharmacokinetic studies after intravenous administration in rats showed significantly lower clearance of DOX from NPs compared with the free DOX group. Tumor targetability of the developed CI NPs was also verified by a real-time optical imaging study. In summary, the chemosensitizing CI/DOX NP with enhanced anticancer activity, prolonged blood circulation, and passive tumor targeting can be a promising anticancer drug delivery system for tumor-targeted therapy. Chemosensitizing nanoparticles (NPs) based on amphiphilic chitosan oligosaccharide-indomethacin (CSO-IDM; CI) conjugate were developed for tumor-targeted delivery of doxorubicin (DOX). IDM was introduced to the CSO backbone as a hydrophobic residue to synthesize an amphiphilic conjugate and a chemosenstizer of DOX for improving antitumor efficacies. IDM, conjugated to CSO, may inhibit the efflux of cellular uptaken DOX via multidrug resistance-associated protein (MRP) and subsequently augment the anti-proliferation potentials of DOX in A549 cells (MRP-expressed human lung cancer cells). Chemosensitizing properties of developed CI NPs were assessed in cell culture models and the tumor targetability of CI/DOX NPs was demonstrated in A549 tumor-xenografted mouse

  3. Diversity of Integrative and Conjugative Elements of Streptococcus salivarius and Their Intra- and Interspecies Transfer.

    Science.gov (United States)

    Dahmane, Narimane; Libante, Virginie; Charron-Bourgoin, Florence; Guédon, Eric; Guédon, Gérard; Leblond-Bourget, Nathalie; Payot, Sophie

    2017-07-01

    Integrative and conjugative elements (ICEs) are widespread chromosomal mobile genetic elements which can transfer autonomously by conjugation in bacteria. Thirteen ICEs with a conjugation module closely related to that of ICE St3 of Streptococcus thermophilus were characterized in Streptococcus salivarius by whole-genome sequencing. Sequence comparison highlighted ICE evolution by shuffling of 3 different integration/excision modules (for integration in the 3' end of the fda , rpsI , or rpmG gene) with the conjugation module of the ICE St3 subfamily. Sequence analyses also pointed out a recombination occurring at oriT (likely mediated by the relaxase) as a mechanism of ICE evolution. Despite a similar organization in two operons including three conserved genes, the regulation modules show a high diversity (about 50% amino acid sequence divergence for the encoded regulators and presence of unrelated additional genes) with a probable impact on the regulation of ICE activity. Concerning the accessory genes, ICEs of the ICE St3 subfamily appear particularly rich in restriction-modification systems and orphan methyltransferase genes. Other cargo genes that could confer a selective advantage to the cell hosting the ICE were identified, in particular, genes for bacteriocin synthesis and cadmium resistance. The functionality of 2 ICEs of S. salivarius was investigated. Autonomous conjugative transfer to other S. salivarius strains, to S. thermophilus , and to Enterococcus faecalis was observed. The analysis of the ICE- fda border sequence in these transconjugants allowed the localization of the DNA cutting site of the ICE integrase. IMPORTANCE The ICE St3 subfamily of ICEs appears to be widespread in streptococci and targets diverse chromosomal integration sites. These ICEs carry diverse cargo genes that can confer a selective advantage to the host strain. The maintenance of these mobile genetic elements likely relies in part on self-encoded restriction

  4. Opto-electronic properties of charged conjugated molecules

    NARCIS (Netherlands)

    Fratiloiu, S.

    2007-01-01

    The aim of this thesis is to provide fundamental insight into the nature and opto-electronic properties of charge carriers on conjugated oligomers and polymers. Electronic structure, optical absorption properties and distribution of charge carriers along the chains of different conjugated materials

  5. Computation of conjugate depths in cubic-shape open channels ...

    African Journals Online (AJOL)

    Determining conjugate depths for a given discharge and initial depth requires the solution of a cubic equation for the conjugate depth and there are currently two approaches to avoiding this difficulty in general. One approach is to iteratively try different depths until one is obtained which gives the same value of the ...

  6. Preparation and characterization of microspheres of albumin-heparin conjugates

    NARCIS (Netherlands)

    Kwon, Glen S.; Bae, You Han; Kim, Sung Wan; Cremers, Harry; Cremers, H.F.M.; Feijen, Jan

    1991-01-01

    Albumin-heparin microspheres have been prepared as a new drug carrier. A soluble albumin-heparin conjugate was synthesized by forming amide bonds between human serum albumin and heparin. After purification the albumin-heparin conjugate was crosslinked in a water-in-oil emulsion to form

  7. Dynamics of nonlinear oscillators with time-varying conjugate coupling

    Indian Academy of Sciences (India)

    We explore the dynamical consequences of time-varying conjugate coupling in a system of nonlinear oscillators. We analyze the behavior of coupled ... Conjugate coupling; time varying coupling. PACS Nos 05.45.Xt. 1. Introduction ..... MDS acknowledges the financial support from DST,. New Delhi. References. [1] L Glass ...

  8. Self-pumped phase-conjugate fiber-optic gyro.

    Science.gov (United States)

    McMichael, I; Yeh, P

    1986-10-01

    We describe a new type of phase-conjugate fiber-optic gyro that uses self-pumped phase conjugation. The selfpumped configuration is simpler than externally pumped configurations and permits the use of sensing fibers longer than the coherence length of the laser. A proof-of-principle demonstration of rotation sensing with the device is presented.

  9. Cross-conjugation and quantum interference : a general correlation?

    NARCIS (Netherlands)

    Valkenier, Hennie; Guedon, Constant M.; Markussen, Troels; Thygesen, Kristian S.; van der Molen, Sense J.; Hummelen, Jan C.

    2014-01-01

    We discuss the relationship between the pi-conjugation pattern, molecular length, and charge transport properties of molecular wires, both from an experimental and a theoretical viewpoint. Specifically, we focus on the role of quantum interference in the conductance properties of cross-conjugated

  10. Chemical conjugation of 2-hexadecynoic acid to C5-curcumin enhances its antibacterial activity against multi-drug resistant bacteria.

    Science.gov (United States)

    Sanabria-Ríos, David J; Rivera-Torres, Yaritza; Rosario, Joshua; Gutierrez, Ricardo; Torres-García, Yeireliz; Montano, Nashbly; Ortíz-Soto, Gabriela; Ríos-Olivares, Eddy; Rodríguez, José W; Carballeira, Néstor M

    2015-11-15

    The first total synthesis of a C5-curcumin-2-hexadecynoic acid (C5-Curc-2-HDA, 6) conjugate was successfully performed. Through a three-step synthetic route, conjugate 6 was obtained in 13% overall yield and tested for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Our results revealed that 6 was active against eight MRSA strains at MICs that range between 31.3 and 62.5 μg/mL. It was found that the presence of 2-hexadecynoic acid (2-HDA, 4) in conjugate 6 increased 4-8-fold its antibacterial activity against MRSA strains supporting our hypothesis that the chemical connection of 4 to C5-curcumin (2) increases the antibacterial activity of 2 against Gram-positive bacteria. Combinational index (CIn) values that range between 1.6 and 2.3 were obtained when eight MRSA strains were treated with an equimolar mixture of 2 and 4. These results demonstrated that an antagonistic effect is taking place. Finally, it was investigated whether conjugate 6 can affect the replication process of S. aureus, since this compound inhibited the supercoiling activity of the S. aureus DNA gyrase at minimum inhibitory concentrations (MIC) of 250 μg/mL (IC50=100.2±13.9 μg/mL). Moreover, it was observed that the presence of 4 in conjugate 6 improves the anti-topoisomerase activity of 2 towards S. aureus DNA gyrase, which is in agreement with results obtained from antibacterial susceptibility tests involving MRSA strains. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Conjugation of cRGD Peptide to Chlorophyll-a Based Photosensitizer (HPPH) Alters its Pharmacokinetics with Enhanced Tumor-Imaging and Photosensitizing (PDT) Efficacy

    Science.gov (United States)

    Srivatsan, Avinash; Ethirajan, Manivannan; Pandey, Suresh K.; Dubey, Shipra; Zheng, Xiang; Liu, Ting-Hsiu; Shibata, Masayuki; Missert, Joseph; Morgan, Janet; Pandey, Ravindra K.

    2011-01-01

    The αvβ3 integrin receptor plays an important role in human metastasis and tumor-induced angiogenesis. Cyclic Arg-Gly-Asp (cRGD) peptide represents a selective αvβ3 integrin ligand that has been extensively used for research, therapy, and diagnosis of neoangiogenesis. For developing photosensitizers with enhanced PDT efficacy, we here report the synthesis of a series of bifunctional agents in which the 3-(1′-hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH), a chlorophyll-based photosensitizer was conjugated to cRGD and the related analogs. The cell uptake, in vitro PDT efficacy of the conjugates were studied in αvβ3 integrin overexpressing U87 and 4T1 cell lines whereas the in vivo PDT efficacy and fluorescence-imaging potential of the conjugates were compared with the corresponding non-conjugated photosensitizer HPPH in 4T1 tumors. Compared to HPPH, the HPPH-cRGD conjugate in which the arginine and aspartic acid moieties were available for binding to two subunits of αvβ3 integrin showed faster clearance, enhanced tumor-imaging and PDT efficacy at 2–4 h post-injection. Molecular modeling studies also confirmed that the presence of HPPH moiety in HPPH-cRGD conjugate does not interfere with specific recognition of cRGD by αvβ3 integrin. Compared to U87 and 4T1 cells the HPPH-cRGD showed significantly low photosensitizing efficacy in A431 (αvβ3 negative) tumor cells, suggesting possible target-specificity of the conjugate. PMID:21702452

  12. Genetic Drift Suppresses Bacterial Conjugation in Spatially Structured Populations

    Science.gov (United States)

    Freese, Peter D.; Korolev, Kirill S.; Jiménez, José I.; Chen, Irene A.

    2014-02-01

    Conjugation is the primary mechanism of horizontal gene transfer that spreads antibiotic resistance among bacteria. Although conjugation normally occurs in surface-associated growth (e.g., biofilms), it has been traditionally studied in well-mixed liquid cultures lacking spatial structure, which is known to affect many evolutionary and ecological processes. Here we visualize spatial patterns of gene transfer mediated by F plasmid conjugation in a colony of Escherichia coli growing on solid agar, and we develop a quantitative understanding by spatial extension of traditional mass-action models. We found that spatial structure suppresses conjugation in surface-associated growth because strong genetic drift leads to spatial isolation of donor and recipient cells, restricting conjugation to rare boundaries between donor and recipient strains. These results suggest that ecological strategies, such as enforcement of spatial structure and enhancement of genetic drift, could complement molecular strategies in slowing the spread of antibiotic resistance genes.

  13. Stimulation of protective antibodies against type Ia and Ib group B streptococci by a type Ia polysaccharide-tetanus toxoid conjugate vaccine.

    OpenAIRE

    Wessels, M R; Paoletti, L C; Rodewald, A K; Michon, F; DiFabio, J; Jennings, H J; Kasper, D L

    1993-01-01

    Antisera elicited by type Ia group B streptococci (GBS) contain antibodies that react with both type Ia and type Ib strains. Previous studies suggested that antibodies elicited by type Ia organisms recognized a carbohydrate antigen or epitope common to Ia and Ib strains. We now report the synthesis and immunogenicity testing of a type Ia polysaccharide-tetanus toxoid (Ia-TT) conjugate vaccine. Ia-TT elicited type Ia polysaccharide-specific immunoglobulin G antibodies in all three of the rabbi...

  14. Fire Synthesis

    Indian Academy of Sciences (India)

    1000ºC or special infrastructure which require careful maintenance. In such a situation fire synthesis is a simpler method that can be adopted for the bulk production of high purity alumina and related oxides. Fire Synthesis. Preparation of Alumina ...

  15. Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in caco-2 cells

    NARCIS (Netherlands)

    Usta, M.; Wortelboer, H.M.; Vervoort, J.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, P.J. van; Cnubben, N.H.P.

    2007-01-01

    Curcumin, an α,β-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional 1H NMR analysis, and

  16. Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in Caco-2 cells

    NARCIS (Netherlands)

    Usta, M.; Wortelboer, H.M.; Vervoort, J.J.M.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, van P.J.; Cnubben, N.H.P.

    2007-01-01

    Curcumin, an alpha,beta-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional H-1 NMR

  17. Impact of Signal-Conjugate Wavelength Shift on Optical Phase Conjugation-based Transmission of QAM Signals

    DEFF Research Database (Denmark)

    Da Ros, Francesco; Lillieholm, Mads; Yankov, Metodi Plamenov

    2017-01-01

    The impact of signal-conjugate wavelength shift on nonlinearity compensation through optical phase conjugation is investigated for 64- and 256-QAM. Wavelength-shift independent achievable rate improvements between 0.2 and 0.3 bit/symbol are reported for shifts up to 30 nm in 500-km transmission....

  18. Ciprofloxacin conjugated zinc oxide nanoparticle: A camouflage ...

    Indian Academy of Sciences (India)

    Gradual development of antibiotic resistant bacteria is producing severe global threat. Newer strategies are now being employed in order to control the microbial infections and to reduce the mortality as well as infection rates. Herein we describe successful synthesis of ZnO nanoparticles (ZNP) under microwave assisted ...

  19. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention?

    Science.gov (United States)

    Miranda, Jonatan; Arias, Noemi; Fernández-Quintela, Alfredo; del Puy Portillo, María

    2014-04-01

    Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after long-term administration. Because of this and the controversial efficacy of CLA in humans, alternative biomolecules that may be used as functional ingredients have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has been reported to be a potential anti-obesity molecule which may have additional positive effects related to obesity. According to the results reported in obesity, CLNA needs to be given at higher doses than CLA to be effective. However, because of the few studies conducted so far, it is still difficult to reach clear conclusions about the potential use of these CLNAs in obesity and its related changes (insulin resistance, dyslipidemia, or inflammation). Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  20. Conjugate Heat Transfer Study in Hypersonic Flows

    Science.gov (United States)

    Sahoo, Niranjan; Kulkarni, Vinayak; Peetala, Ravi Kumar

    2018-04-01

    Coupled and decoupled conjugate heat transfer (CHT) studies are carried out to imitate experimental studies for heat transfer measurement in hypersonic flow regime. The finite volume based solvers are used for analyzing the heat interaction between fluid and solid domains. Temperature and surface heat flux signals are predicted by both coupled and decoupled CHT analysis techniques for hypersonic Mach numbers. These two methodologies are also used to study the effect of different wall materials on surface parameters. Effectiveness of these CHT solvers has been verified for the inverse problem of wall heat flux recovery using various techniques reported in the literature. Both coupled and decoupled CHT techniques are seen to be equally useful for prediction of local temperature and heat flux signals prior to the experiments in hypersonic flows.