LASSO—ligand activity by surface similarity order: a new tool for ligand based virtual screening

Science.gov (United States)

Reid, Darryl; Sadjad, Bashir S.; Zsoldos, Zsolt; Simon, Aniko

2008-06-01

Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

Covalent Coupling of Nanoparticles with Low-Density Functional Ligands to Surfaces via Click Chemistry

NARCIS (Netherlands)

Rianasari, I.; de Jong, Machiel Pieter; Huskens, Jurriaan; van der Wiel, Wilfred Gerard

2013-01-01

We demonstrate the application of the 1,3-dipolar cycloaddition (“click‿ reaction) to couple gold nanoparticles (Au NPs) functionalized with low densities of functional ligands. The ligand coverage on the citrate-stabilized Au NPs was adjusted by the ligand:Au surface atom ratio, while maintaining

Functionalization of Cadmium Selenide Quantum Dots with Poly(ethylene glycol): Ligand Exchange, Surface Coverage, and Dispersion Stability.

Science.gov (United States)

Wenger, Whitney Nowak; Bates, Frank S; Aydil, Eray S

2017-08-22

Semiconductor quantum dots synthesized using rapid mixing of precursors by injection into a hot solution of solvents and surfactants have surface ligands that sterically stabilize the dispersions in nonpolar solvents. Often, these ligands are exchanged to disperse the quantum dots in polar solvents, but quantitative studies of quantum dot surfaces before and after ligand exchange are scarce. We studied exchanging trioctylphosphine (TOP) and trioctylphosphine oxide (TOPO) ligands on as-synthesized CdSe quantum dots dispersed in hexane with a 2000 g/mol thiolated poly(ethylene glycol) (PEG) polymer. Using infrared spectroscopy we quantify the absolute surface concentration of TOP/TOPO and PEG ligands per unit area before and after ligand exchange. While 50-85% of the TOP/TOPO ligands are removed upon ligand exchange, only a few are replaced with PEG. Surprisingly, the remaining TOP/TOPO ligands outnumber the PEG ligands, but these few PEG ligands are sufficient to disperse the quantum dots in polar solvents such as chloroform, tetrahydrofuran, and water. Moreover, as-synthesized quantum dots once easily dispersed in hexane are no longer dispersible in nonpolar solvents after ligand exchange. A subtle coverage-dependent balance between attractive PEG-solvent interactions and repulsive TOP/TOPO-solvent interactions determines the dispersion stability.

Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor

DEFF Research Database (Denmark)

Bokoch, Michael P; Zou, Yaozhong; Rasmussen, Søren Gøgsig Faarup

2010-01-01

extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known...... conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive...... about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the beta(2) adrenergic...

Detecting local ligand-binding site similarity in nonhomologous proteins by surface patch comparison.

Science.gov (United States)

Sael, Lee; Kihara, Daisuke

2012-04-01

Functional elucidation of proteins is one of the essential tasks in biology. Function of a protein, specifically, small ligand molecules that bind to a protein, can be predicted by finding similar local surface regions in binding sites of known proteins. Here, we developed an alignment free local surface comparison method for predicting a ligand molecule which binds to a query protein. The algorithm, named Patch-Surfer, represents a binding pocket as a combination of segmented surface patches, each of which is characterized by its geometrical shape, the electrostatic potential, the hydrophobicity, and the concaveness. Representing a pocket by a set of patches is effective to absorb difference of global pocket shape while capturing local similarity of pockets. The shape and the physicochemical properties of surface patches are represented using the 3D Zernike descriptor, which is a series expansion of mathematical 3D function. Two pockets are compared using a modified weighted bipartite matching algorithm, which matches similar patches from the two pockets. Patch-Surfer was benchmarked on three datasets, which consist in total of 390 proteins that bind to one of 21 ligands. Patch-Surfer showed superior performance to existing methods including a global pocket comparison method, Pocket-Surfer, which we have previously introduced. Particularly, as intended, the accuracy showed large improvement for flexible ligand molecules, which bind to pockets in different conformations. Copyright © 2011 Wiley Periodicals, Inc.

Sulfur ligand mediated electrochemistry of gold surfaces and nanoparticles: what, how, and why

DEFF Research Database (Denmark)

Chi, Qijin; Ford, Michael J.; Halder, Arnab

2017-01-01

Gold surfaces are widely used in electrochemistry whilst gold nanoparticles have very many uses, with both the surfaces and the particles often being protected by sulfur-bound organic ligands. The ligands not only provide chemical stability but also directly participate in many desired processes....... This review considers the diversity of known atomic structures for gold-sulfur interfaces, how these structures facilitate a diversity of mechanisms in electrochemical applications, and why this is possible based on recent advances in the basic understanding of the electronic structure of gold-sulfur bonds...

Detecting Local Ligand-Binding Site Similarity in Non-Homologous Proteins by Surface Patch Comparison

Science.gov (United States)

Sael, Lee; Kihara, Daisuke

2012-01-01

Functional elucidation of proteins is one of the essential tasks in biology. Function of a protein, specifically, small ligand molecules that bind to a protein, can be predicted by finding similar local surface regions in binding sites of known proteins. Here, we developed an alignment free local surface comparison method for predicting a ligand molecule which binds to a query protein. The algorithm, named Patch-Surfer, represents a binding pocket as a combination of segmented surface patches, each of which is characterized by its geometrical shape, the electrostatic potential, the hydrophobicity, and the concaveness. Representing a pocket by a set of patches is effective to absorb difference of global pocket shape while capturing local similarity of pockets. The shape and the physicochemical properties of surface patches are represented using the 3D Zernike descriptor, which is a series expansion of mathematical 3D function. Two pockets are compared using a modified weighted bipartite matching algorithm, which matches similar patches from the two pockets. Patch-Surfer was benchmarked on three datasets, which consist in total of 390 proteins that bind to one of 21 ligands. Patch-Surfer showed superior performance to existing methods including a global pocket comparison method, Pocket-Surfer, which we have previously introduced. Particularly, as intended, the accuracy showed large improvement for flexible ligand molecules, which bind to pockets in different conformations. PMID:22275074

Deciphering ligands' interaction with Cu and Cu2O nanocrystal surfaces by NMR solution tools.

Science.gov (United States)

Glaria, Arnaud; Cure, Jérémy; Piettre, Kilian; Coppel, Yannick; Turrin, Cédric-Olivier; Chaudret, Bruno; Fau, Pierre

2015-01-12

The hydrogenolysis of [Cu2{(iPrN)2(CCH3)}2] in the presence of hexadecylamine (HDA) or tetradecylphosphonic acid (TDPA) in toluene leads to 6-9 nm copper nanocrystals. Solution NMR spectroscopy has been used to describe the nanoparticle surface chemistry during the dynamic phenomenon of air oxidation. The ligands are organized as multilayered shells around the nanoparticles. The shell of ligands is controlled by both their intermolecular interactions and their bonding strength on the nanocrystals. Under ambient atmosphere, the oxidation rate of colloidal copper nanocrystals closely relies on the chemical nature of the employed ligands (base or acid). Primary amine molecules behave as soft ligands for Cu atoms, but are even more strongly coordinated on surface Cu(I) sites, thus allowing a very efficient corrosion protection of the copper core. On the contrary, the TDPA ligands lead to a rapid oxidation rate of Cu nanoparticles and eventually to the re-dissolution of Cu(II) species at the expense of the nanocrystals. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

LIGSITEcsc: predicting ligand binding sites using the Connolly surface and degree of conservation

Directory of Open Access Journals (Sweden)

Schroeder Michael

2006-09-01

Full Text Available Abstract Background Identifying pockets on protein surfaces is of great importance for many structure-based drug design applications and protein-ligand docking algorithms. Over the last ten years, many geometric methods for the prediction of ligand-binding sites have been developed. Results We present LIGSITEcsc, an extension and implementation of the LIGSITE algorithm. LIGSITEcsc is based on the notion of surface-solvent-surface events and the degree of conservation of the involved surface residues. We compare our algorithm to four other approaches, LIGSITE, CAST, PASS, and SURFNET, and evaluate all on a dataset of 48 unbound/bound structures and 210 bound-structures. LIGSITEcsc performs slightly better than the other tools and achieves a success rate of 71% and 75%, respectively. Conclusion The use of the Connolly surface leads to slight improvements, the prediction re-ranking by conservation to significant improvements of the binding site predictions. A web server for LIGSITEcsc and its source code is available at scoppi.biotec.tu-dresden.de/pocket.

5D-QSAR for spirocyclic sigma1 receptor ligands by Quasar receptor surface modeling.

Science.gov (United States)

Oberdorf, Christoph; Schmidt, Thomas J; Wünsch, Bernhard

2010-07-01

Based on a contiguous and structurally as well as biologically diverse set of 87 sigma(1) ligands, a 5D-QSAR study was conducted in which a quasi-atomistic receptor surface modeling approach (program package Quasar) was applied. The superposition of the ligands was performed with the tool Pharmacophore Elucidation (MOE-package), which takes all conformations of the ligands into account. This procedure led to four pharmacophoric structural elements with aromatic, hydrophobic, cationic and H-bond acceptor properties. Using the aligned structures a 3D-model of the ligand binding site of the sigma(1) receptor was obtained, whose general features are in good agreement with previous assumptions on the receptor structure, but revealed some novel insights since it represents the receptor surface in more detail. Thus, e.g., our model indicates the presence of an H-bond acceptor moiety in the binding site as counterpart to the ligands' cationic ammonium center, rather than a negatively charged carboxylate group. The presented QSAR model is statistically valid and represents the biological data of all tested compounds, including a test set of 21 ligands not used in the modeling process, with very good to excellent accuracy [q(2) (training set, n=66; leave 1/3 out) = 0.84, p(2) (test set, n=21)=0.64]. Moreover, the binding affinities of 13 further spirocyclic sigma(1) ligands were predicted with reasonable accuracy (mean deviation in pK(i) approximately 0.8). Thus, in addition to novel insights into the requirements for binding of spirocyclic piperidines to the sigma(1) receptor, the presented model can be used successfully in the rational design of new sigma(1) ligands. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Group IV nanocrystals with ion-exchangeable surface ligands and methods of making the same

Science.gov (United States)

Wheeler, Lance M.; Nichols, Asa W.; Chernomordik, Boris D.; Anderson, Nicholas C.; Beard, Matthew C.; Neale, Nathan R.

2018-01-09

Methods are described that include reacting a starting nanocrystal that includes a starting nanocrystal core and a covalently bound surface species to create an ion-exchangeable (IE) nanocrystal that includes a surface charge and a first ion-exchangeable (IE) surface ligand ionically bound to the surface charge, where the starting nanocrystal core includes a group IV element.

Elucidating the role of surface passivating ligand structural parameters in hole wave function delocalization in semiconductor cluster molecules.

Science.gov (United States)

Teunis, Meghan B; Nagaraju, Mulpuri; Dutta, Poulami; Pu, Jingzhi; Muhoberac, Barry B; Sardar, Rajesh; Agarwal, Mangilal

2017-09-28

This article describes the mechanisms underlying electronic interactions between surface passivating ligands and (CdSe) 34 semiconductor cluster molecules (SCMs) that facilitate band-gap engineering through the delocalization of hole wave functions without altering their inorganic core. We show here both experimentally and through density functional theory calculations that the expansion of the hole wave function beyond the SCM boundary into the ligand monolayer depends not only on the pre-binding energetic alignment of interfacial orbitals between the SCM and surface passivating ligands but is also strongly influenced by definable ligand structural parameters such as the extent of their π-conjugation [π-delocalization energy; pyrene (Py), anthracene (Anth), naphthalene (Naph), and phenyl (Ph)], binding mode [dithiocarbamate (DTC, -NH-CS 2 - ), carboxylate (-COO - ), and amine (-NH 2 )], and binding head group [-SH, -SeH, and -TeH]. We observe an unprecedentedly large ∼650 meV red-shift in the lowest energy optical absorption band of (CdSe) 34 SCMs upon passivating their surface with Py-DTC ligands and the trend is found to be Ph- wave function delocalization rather than carrier trapping and/or phonon-mediated relaxation. Taken together, knowledge of how ligands electronically interact with the SCM surface is crucial to semiconductor nanomaterial research in general because it allows the tuning of electronic properties of nanomaterials for better charge separation and enhanced charge transfer, which in turn will increase optoelectronic device and photocatalytic efficiencies.

Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor

Energy Technology Data Exchange (ETDEWEB)

Bokoch, Michael P.; Zou, Yaozhong; Rasmussen, Søren G.F.; Liu, Corey W.; Nygaard, Rie; Rosenbaum, Daniel M.; Fung, Juan José; Choi, Hee-Jung; Thian, Foon Sun; Kobilka, Tong Sun; Puglisi, Joseph D.; Weis, William I.; Pardo, Leonardo; Prosser, R. Scott; Mueller, Luciano; Kobilka, Brian K. (Stanford-MED); (Toronto); (BMS); (UAB, Spain)

2010-01-14

G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs have revealed structural conservation extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the {beta}{sub 2} adrenergic receptor: a salt bridge linking extracellular loops 2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit different efficacies towards G-protein activation (agonist, neutral antagonist and inverse agonist) also stabilize distinct conformations of the ECS. We thereby demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive-state crystal structures.

Enhancing the Performance of CdSe/CdS Dot-in-Rod Light-Emitting Diodes via Surface Ligand Modification.

Science.gov (United States)

Rastogi, Prachi; Palazon, Francisco; Prato, Mirko; Di Stasio, Francesco; Krahne, Roman

2018-02-14

The surface ligands on colloidal nanocrystals (NCs) play an important role in the performance of NC-based optoelectronic devices such as photovoltaic cells, photodetectors, and light-emitting diodes (LEDs). On one hand, the NC emission depends critically on the passivation of the surface to minimize trap states that can provide nonradiative recombination channels. On the other hand, the electrical properties of NC films are dominated by the ligands that constitute the barriers for charge transport from one NC to its neighbor. Therefore, surface modifications via ligand exchange have been employed to improve the conductance of NC films. However, in LEDs, such surface modifications are more critical because of their possible detrimental effects on the emission properties. In this work, we study the role of surface ligand modifications on the optical and electrical properties of CdSe/CdS dot-in-rods (DiRs) in films and investigate their performance in all-solution-processed LEDs. The DiR films maintain high photoluminescence quantum yield, around 40-50%, and their electroluminescence in the LED preserves the excellent color purity of the photoluminescence. In the LEDs, the ligand exchange boosted the luminance, reaching a fourfold increase from 2200 cd/m 2 for native surfactants to 8500 cd/m 2 for the exchanged aminoethanethiol (AET) ligands. Moreover, the efficiency roll-off, operational stability, and shelf life are significantly improved, and the external quantum efficiency is modestly increased from 5.1 to 5.4%. We relate these improvements to the increased conductivity of the emissive layer and to the better charge balance of the electrically injected carriers. In this respect, we performed ultraviolet photoelectron spectroscopy (UPS) to obtain a deeper insight into the band alignment of the LED structure. The UPS data confirm similar flat-band offsets of the emitting layer to the electron- and hole-transport layers in the case of AET ligands, which translates to

Spectroscopic characterization of ligands on the surface of water dispersible NaGdF4:Ln3+ nanocrystals

International Nuclear Information System (INIS)

Cichos, J.; Karbowiak, M.

2012-01-01

For electronic or biomedical applications it is desirable to have ligand-free water-dispersible nanocrystals (NCs). The commonly used FTIR spectroscopy often provides a direct evidence for molecules on the surface. In some cases, however, the strong bands of solvent molecules may obscure the peaks of surface bounded ligands. We show that in this regard the emission spectroscopy may be used as a more reliable probing tool. The relevant information can be obtained from emission and excitation spectra, emission decay times as well as from analysis of relative efficiency of excitation energy transfer from Gd 3+ to Eu 3+ ions. Using these methods we tested samples obtained by various synthetic routes and indicated that only nitrosonium tetrafluoroborate (NOBF 4 ) removes successfully the organic ligands from the nanocrystals surface, yielding organic ligand-free NCs dispersible in aqueous solutions. The conclusions drawn from emission spectroscopy are useful for interpretation of results of FTIR, Raman and NMR studies. The detailed assignment of FTIR peaks for oleate-capped and oleate-free NCs is also provided. Finally, we point to the risk of drawing erroneous conclusions about colloidal stability of nanocrystals if refractive indexes of NCs and medium are similar.

Spectroscopic characterization of ligands on the surface of water dispersible NaGdF4:Ln3+ nanocrystals

Science.gov (United States)

Cichos, J.; Karbowiak, M.

2012-05-01

For electronic or biomedical applications it is desirable to have ligand-free water-dispersible nanocrystals (NCs). The commonly used FTIR spectroscopy often provides a direct evidence for molecules on the surface. In some cases, however, the strong bands of solvent molecules may obscure the peaks of surface bounded ligands. We show that in this regard the emission spectroscopy may be used as a more reliable probing tool. The relevant information can be obtained from emission and excitation spectra, emission decay times as well as from analysis of relative efficiency of excitation energy transfer from Gd3+ to Eu3+ ions. Using these methods we tested samples obtained by various synthetic routes and indicated that only nitrosonium tetrafluoroborate (NOBF4) removes successfully the organic ligands from the nanocrystals surface, yielding organic ligand-free NCs dispersible in aqueous solutions. The conclusions drawn from emission spectroscopy are useful for interpretation of results of FTIR, Raman and NMR studies. The detailed assignment of FTIR peaks for oleate-capped and oleate-free NCs is also provided. Finally, we point to the risk of drawing erroneous conclusions about colloidal stability of nanocrystals if refractive indexes of NCs and medium are similar.

Using surfaces, ligands, and dimensionality to obtain desired nanostructure properties

Science.gov (United States)

Nagpal, Prashant; Singh, Vivek; Ding, Yuchen

2014-03-01

Nanostructured materials are intensively investigated to obtain material properties different from their bulk counterparts. It has been demonstrated that nanoscaled semiconductor can have interesting size, shape and morphology dependent optoelectronic properties. But the effect of surfaces, ligands and dimensionality (0D quantum dots to 2D nanosheets) has been largely unexplored. Here, we will show how tuning the surface and dimensionality can affect the electronic states of the semiconductor, and how these states can play an important role in their fundamental photophysical properties or thermal transport. Using the specific case for silicon, we will show how ``new'' surface states in small uniform can lead to light absorption/emission without phonon assistance, while hindering the phonon-drag of charge carriers leading to low Seebeck coefficient for thermoelectric applications. These measurements will shed light on designing appropriate surface, size, and dimensionality for desired applications of nanostructured films.

In situ spectroscopy of ligand exchange reactions at the surface of colloidal gold and silver nanoparticles

International Nuclear Information System (INIS)

Dinkel, Rebecca; Peukert, Wolfgang; Braunschweig, Björn

2017-01-01

Gold and silver nanoparticles with their tunable optical and electronic properties are of great interest for a wide range of applications. Often the ligands at the surface of the nanoparticles have to be exchanged in a second step after particle formation in order to obtain a desired surface functionalization. For many techniques, this process is not accessible in situ . In this review, we present second-harmonic scattering (SHS) as an inherently surface sensitive and label-free optical technique to probe the ligand exchange at the surface of colloidal gold and silver nanoparticles in situ and in real time. First, a brief introduction to SHS and basic features of the SHS of nanoparticles are given. After that, we demonstrate how the SHS intensity decrease can be correlated to the thiol coverage which allows for the determination of the Gibbs free energy of adsorption and the surface coverage. (topical review)

Surface control of blastospore attachment and ligand-mediated hyphae adhesion of Candida albicans.

Science.gov (United States)

Varghese, Nisha; Yang, Sijie; Sejwal, Preeti; Luk, Yan-Yeung

2013-11-14

Adhesion on a surface via nonspecific attachment or multiple ligand-receptor interactions is a critical event for fungal infection by Candida albicans. Here, we find that the tri(ethylene glycol)- and d-mannitol-terminated monolayers do not resist the blastospore attachment, but prevent the hyphae adhesion of C. albicans. The hyphae adhesion can be facilitated by tripeptide sequences of arginine-glycine-aspartic acid (RGD) covalently decorated on a background of tri(ethylene glycol)-terminated monolayers. This adhesion mediated by selected ligands is sensitive to the scrambling of peptide sequences, and is inhibited by the presence of cyclic RGD peptides in the solution.

Predicting Ligand Binding Sites on Protein Surfaces by 3-Dimensional Probability Density Distributions of Interacting Atoms

Science.gov (United States)

Jian, Jhih-Wei; Elumalai, Pavadai; Pitti, Thejkiran; Wu, Chih Yuan; Tsai, Keng-Chang; Chang, Jeng-Yih; Peng, Hung-Pin; Yang, An-Suei

2016-01-01

Predicting ligand binding sites (LBSs) on protein structures, which are obtained either from experimental or computational methods, is a useful first step in functional annotation or structure-based drug design for the protein structures. In this work, the structure-based machine learning algorithm ISMBLab-LIG was developed to predict LBSs on protein surfaces with input attributes derived from the three-dimensional probability density maps of interacting atoms, which were reconstructed on the query protein surfaces and were relatively insensitive to local conformational variations of the tentative ligand binding sites. The prediction accuracy of the ISMBLab-LIG predictors is comparable to that of the best LBS predictors benchmarked on several well-established testing datasets. More importantly, the ISMBLab-LIG algorithm has substantial tolerance to the prediction uncertainties of computationally derived protein structure models. As such, the method is particularly useful for predicting LBSs not only on experimental protein structures without known LBS templates in the database but also on computationally predicted model protein structures with structural uncertainties in the tentative ligand binding sites. PMID:27513851

Surface polyPEGylation of Eu"3"+ doped luminescent hydroxyapatite nanorods through the combination of ligand exchange and metal free surface initiated atom transfer radical polymerization

International Nuclear Information System (INIS)

Zeng, Guangjian; Liu, Meiying; Heng, Chunning; Huang, Qiang; Mao, Liucheng; Huang, Hongye; Hui, Junfeng; Deng, Fengjie; Zhang, Xiaoyong; Wei, Yen

2017-01-01

Highlights: • Surface modification of HAp nanorods through the combination of ligand exchange reaction and metal free SI-ATRP. • HAp-polyPEGMA displayed high water dispersibility, good biocompatibility and biological imaging capability. • Metal free ATRP can overcome the toxic and fluorescence quenching effects of metal catalysts of conventional ATRP. - Abstract: The Eu"3"+ doped luminescent hydroxyapatite (HAp) nanorods with uniform size and morphology can be synthesized by hydrothermal route. However, these HAp nanorods are coated by hydrophobic oleylamine, which makes them difficult to be dispersed in aqueous solution and impede their biomedical applications. In this work, Eu"3"+ doped luminescent polymers functionalized HAp nanorods were prepared through the combination of ligand exchange reaction and metal free surface initiated atom transfer radical polymerization (ATRP) method. In this procedure, the amino group functionalized HAp nanorods were first prepared by ligand exchange reaction using adenosine monophosphate (AMP) as ligand. Then the Br-containing initiators (HAp-Br) were introduced onto the surface of HAp-AMP nanorods through the amidation reaction. Finally, polymers functionalized HAp nanorods were prepared by metal free ATRP method using poly(ethylene glycol) methacrylate (PEGMA) as monomer and 10-phenylphenothiazine (PTH) as organic photocatalyst. The properties of these obtained HAp nanocomposites (HAP-polyPEGMA nanorods) were characterized by means of transmission electron microscopy, Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy and thermogravimetric analysis in detail. The cell imaging of these HAP-polyPEGMA nanorods was examined using laser scanning confocal microscope to evaluate their biomedical applications. We demonstrated for the first time that hydrophobic luminescent HAp nanorods can be functionalized with polyPEGMA through the combination of ligand exchange reaction and metal free surface initiated

Origin of the Substitution Mechanism for the Binding of Organic Ligands on the Surface of CsPbBr3 Perovskite Nanocubes.

Science.gov (United States)

Ravi, Vikash Kumar; Santra, Pralay K; Joshi, Niharika; Chugh, Jeetender; Singh, Sachin Kumar; Rensmo, Håkan; Ghosh, Prasenjit; Nag, Angshuman

2017-10-19

Optoelectronic properties of CsPbBr 3 perovskite nanocubes (NCs) depend strongly on the interaction of the organic passivating molecules with the inorganic crystal. To understand this interaction, we employed a combination of synchrotron-based X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance (NMR) spectroscopy, and first-principles density functional theory (DFT)-based calculations. Variable energy XPS elucidated the internal structure of the inorganic part in a layer-by-layer fashion, whereas NMR characterized the organic ligands. Our experimental results confirm that oleylammonium ions act as capping ligands by substituting Cs + ions from the surface of CsPbBr 3 NCs. DFT calculations shows that the substitution mechanism does not require much energy for surface reconstruction and, in contrast, stabilizes the nanocrystal by the formation of three hydrogen bonds between the -NH 3 + moiety of oleylammonium and surrounding Br - on the surface of NCs. This substitution mechanism and its origin are in stark contrast to the usual adsorption of organic ligands on the surface of typical NCs.

Significant Enhancement of the Chiral Correlation Length in Nematic Liquid Crystals by Gold Nanoparticle Surfaces Featuring Axially Chiral Binaphthyl Ligands.

Science.gov (United States)

Mori, Taizo; Sharma, Anshul; Hegmann, Torsten

2016-01-26

Chirality is a fundamental scientific concept best described by the absence of mirror symmetry and the inability to superimpose an object onto its mirror image by translation and rotation. Chirality is expressed at almost all molecular levels, from single molecules to supramolecular systems, and present virtually everywhere in nature. Here, to explore how chirality propagates from a chiral nanoscale surface, we study gold nanoparticles functionalized with axially chiral binaphthyl molecules. In particular, we synthesized three enantiomeric pairs of chiral ligand-capped gold nanoparticles differing in size, curvature, and ligand density to tune the chirality transfer from nanoscale solid surfaces to a bulk anisotropic liquid crystal medium. Ultimately, we are examining how far the chirality from a nanoparticle surface reaches into a bulk material. Circular dichroism spectra of the gold nanoparticles decorated with binaphthyl thiols confirmed that the binaphthyl moieties form a cisoid conformation in isotropic organic solvents. In the chiral nematic liquid crystal phase, induced by dispersing the gold nanoparticles into an achiral anisotropic nematic liquid crystal solvent, the binaphthyl moieties on the nanoparticle surface form a transoid conformation as determined by imaging the helical twist direction of the induced cholesteric phase. This suggests that the ligand density on the nanoscale metal surfaces provides a dynamic space to alter and adjust the helicity of binaphthyl derivatives in response to the ordering of the surrounding medium. The helical pitch values of the induced chiral nematic phase were determined, and the helical twisting power (HTP) of the chiral gold nanoparticles calculated to elucidate the chirality transfer efficiency of the binaphthyl ligand capped gold nanoparticles. Remarkably, the HTP increases with increasing diameter of the particles, that is, the efficiency of the chirality transfer of the binaphthyl units bound to the nanoparticle

29-Silicon NMR evidence for the improved chromatographic siloxane bond stability of bulky alkylsilane ligands on a silica surface

NARCIS (Netherlands)

Scholten, A.B.; Haan, de J.W.; Claessens, H.A.; Ven, van de L.J.M.; Cramers, C.A.

1994-01-01

A stable bond stationary phase for reversed-phase HPLC, with a diisobutyl-n-octadecylsilane derivatized surface, was studied using 29Si CPMAS NMR. Fumed silica surfaces (Aerosil), trimethylsilylated to different extents, were used to illustrate the effect of ligand surface loading on the hydrogen

Surface polyPEGylation of Eu{sup 3+} doped luminescent hydroxyapatite nanorods through the combination of ligand exchange and metal free surface initiated atom transfer radical polymerization

Energy Technology Data Exchange (ETDEWEB)

Zeng, Guangjian; Liu, Meiying [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Heng, Chunning [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi’an 710069 (China); Huang, Qiang; Mao, Liucheng; Huang, Hongye [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Hui, Junfeng [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi’an 710069 (China); Deng, Fengjie, E-mail: fengjiedeng@aliyun.com [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Zhang, Xiaoyong, E-mail: xiaoyongzhang1980@gmail.com [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wei, Yen, E-mail: weiyen@tsinghua.edu.cn [Department of Chemistry and The Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China)

2017-03-31

Highlights: • Surface modification of HAp nanorods through the combination of ligand exchange reaction and metal free SI-ATRP. • HAp-polyPEGMA displayed high water dispersibility, good biocompatibility and biological imaging capability. • Metal free ATRP can overcome the toxic and fluorescence quenching effects of metal catalysts of conventional ATRP. - Abstract: The Eu{sup 3+} doped luminescent hydroxyapatite (HAp) nanorods with uniform size and morphology can be synthesized by hydrothermal route. However, these HAp nanorods are coated by hydrophobic oleylamine, which makes them difficult to be dispersed in aqueous solution and impede their biomedical applications. In this work, Eu{sup 3+} doped luminescent polymers functionalized HAp nanorods were prepared through the combination of ligand exchange reaction and metal free surface initiated atom transfer radical polymerization (ATRP) method. In this procedure, the amino group functionalized HAp nanorods were first prepared by ligand exchange reaction using adenosine monophosphate (AMP) as ligand. Then the Br-containing initiators (HAp-Br) were introduced onto the surface of HAp-AMP nanorods through the amidation reaction. Finally, polymers functionalized HAp nanorods were prepared by metal free ATRP method using poly(ethylene glycol) methacrylate (PEGMA) as monomer and 10-phenylphenothiazine (PTH) as organic photocatalyst. The properties of these obtained HAp nanocomposites (HAP-polyPEGMA nanorods) were characterized by means of transmission electron microscopy, Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy and thermogravimetric analysis in detail. The cell imaging of these HAP-polyPEGMA nanorods was examined using laser scanning confocal microscope to evaluate their biomedical applications. We demonstrated for the first time that hydrophobic luminescent HAp nanorods can be functionalized with polyPEGMA through the combination of ligand exchange reaction and metal free surface

Surface ligand dependent toxicity of zinc oxide nanoparticles in HepG2 cell model

International Nuclear Information System (INIS)

Bartczak, D; Baradez, M-O; Merson, S; Goenaga-Infante, H; Marshall, D

2013-01-01

Physicochemical properties of nanoparticles (NP) strongly affect their influence on cell behaviour, but can be significantly distorted by interactions with the proteins present in biological solutions. In this study we show how different surface functionalities of zinc oxide (ZnO) NP lead to changes in the size distribution and dissolution of the NP in serum containing cell culture media and how this impacts on NP toxicity. NPs capped with weakly bound large proteins undergo substantial transformations due to the exchange of the original surface ligands to the components of the cell culture media. Conversely, NP capped with a tight monolayer of small organic molecules or with covalently conjugated proteins show significantly higher stability. These differences in ligand exchange also affect the toxicity of the NP to the HepG2 liver cell model, with the NP capped with small organic molecules being more toxic than those capped with large proteins. This study highlights the importance of characterising NPs in biological media and the effect the media has during in-vitro analysis.

"Precipitation on Nanoparticles": Attractive Intermolecular Interactions Stabilize Specific Ligand Ratios on the Surfaces of Nanoparticles.

Science.gov (United States)

Chu, Zonglin; Han, Yanxiao; Kral, Petr; Klajn, Rafal

2018-04-19

Confining organic molecules to the surfaces of inorganic nanoparticles can induce intermolecular interactions between them, which can affect the composition of the mixed self-assembled monolayers obtained by co-adsorption from solution of two different molecules. Here, we study co-adsorption of two thiolated ligands-a dialkylviologen and a zwitterionic sulfobetaine-that can interact with each other electrostatically, onto gold nanoparticles. Consequently, the nanoparticles favor a narrow range of ratios of these two molecules that is largely independent of the molar ratio in solution. We show that changing the solution molar ratio of two ligands by a factor of ~5,000 affects the on-nanoparticle ratio of these ligands by only 3 times. This behavior is reminiscent of the formation of insoluble inorganic salts (e.g., AgCl), which similarly compensate positive and negative charges upon crystallizing. Our results pave the way towards developing well-defined hybrid organic-inorganic nanostructures. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of surface ligands in determining the electronic properties of quantum dot solids and their impact on photovoltaic figure of merits.

Science.gov (United States)

Goswami, Prasenjit N; Mandal, Debranjan; Rath, Arup K

2018-01-18

Surface chemistry plays a crucial role in determining the electronic properties of quantum dot solids and may well be the key to mitigate loss processes involved in quantum dot solar cells. Surface ligands help to maintain the shape and size of the individual dots in solid films, to preserve the clean energy band gap of the individual particles and to control charge carrier conduction across solid films, in turn regulating their performance in photovoltaic applications. In this report, we show that the changes in size, shape and functional groups of small chain organic ligands enable us to modulate mobility, dielectric constant and carrier doping density of lead sulfide quantum dot solids. Furthermore, we correlate these results with performance, stability and recombination processes in the respective photovoltaic devices. Our results highlight the critical role of surface chemistry in the electronic properties of quantum dots. The role of the size, functionality and the surface coverage of the ligands in determining charge transport properties and the stability of quantum dot solids have been discussed. Our findings, when applied in designing new ligands with higher mobility and improved passivation of quantum dot solids, can have important implications for the development of high-performance quantum dot solar cells.

Surface polyPEGylation of Eu3+ doped luminescent hydroxyapatite nanorods through the combination of ligand exchange and metal free surface initiated atom transfer radical polymerization

Science.gov (United States)

Zeng, Guangjian; Liu, Meiying; Heng, Chunning; Huang, Qiang; Mao, Liucheng; Huang, Hongye; Hui, Junfeng; Deng, Fengjie; Zhang, Xiaoyong; Wei, Yen

2017-03-01

The Eu3+ doped luminescent hydroxyapatite (HAp) nanorods with uniform size and morphology can be synthesized by hydrothermal route. However, these HAp nanorods are coated by hydrophobic oleylamine, which makes them difficult to be dispersed in aqueous solution and impede their biomedical applications. In this work, Eu3+ doped luminescent polymers functionalized HAp nanorods were prepared through the combination of ligand exchange reaction and metal free surface initiated atom transfer radical polymerization (ATRP) method. In this procedure, the amino group functionalized HAp nanorods were first prepared by ligand exchange reaction using adenosine monophosphate (AMP) as ligand. Then the Br-containing initiators (HAp-Br) were introduced onto the surface of HAp-AMP nanorods through the amidation reaction. Finally, polymers functionalized HAp nanorods were prepared by metal free ATRP method using poly(ethylene glycol) methacrylate (PEGMA) as monomer and 10-phenylphenothiazine (PTH) as organic photocatalyst. The properties of these obtained HAp nanocomposites (HAP-polyPEGMA nanorods) were characterized by means of transmission electron microscopy, Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy and thermogravimetric analysis in detail. The cell imaging of these HAP-polyPEGMA nanorods was examined using laser scanning confocal microscope to evaluate their biomedical applications. We demonstrated for the first time that hydrophobic luminescent HAp nanorods can be functionalized with polyPEGMA through the combination of ligand exchange reaction and metal free surface initiated ATRP. As compared with the traditional ATRP, the metal free ATRP can overcome the toxic and fluorescence quenching effects of metal catalysts such as copper ions. More importantly, the strategy described in this work should also be utilized for fabrications of many other luminescent polymer nanocomposites due to its good monomer adoptability.

A conserved WW domain-like motif regulates invariant chain-dependent cell-surface transport of the NKG2D ligand ULBP2.

Science.gov (United States)

Uhlenbrock, Franziska; van Andel, Esther; Andresen, Lars; Skov, Søren

2015-08-01

Malignant cells expressing NKG2D ligands on their cell surface can be directly sensed and killed by NKG2D-bearing lymphocytes. To ensure this immune recognition, accumulating evidence suggests that NKG2D ligands are trafficed via alternative pathways to the cell surface. We have previously shown that the NKG2D ligand ULBP2 traffics over an invariant chain (Ii)-dependent pathway to the cell surface. This study set out to elucidate how Ii regulates ULBP2 cell-surface transport: We discovered conserved tryptophan (Trp) residues in the primary protein sequence of ULBP1-6 but not in the related MICA/B. Substitution of Trp to alanine resulted in cell-surface inhibition of ULBP2 in different cancer cell lines. Moreover, the mutated ULBP2 constructs were retained and not degraded inside the cell, indicating a crucial role of this conserved Trp-motif in trafficking. Finally, overexpression of Ii increased surface expression of wt ULBP2 while Trp-mutants could not be expressed, proposing that this Trp-motif is required for an Ii-dependent cell-surface transport of ULBP2. Aberrant soluble ULBP2 is immunosuppressive. Thus, targeting a distinct protein module on the ULBP2 sequence could counteract this abnormal expression of ULBP2. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of Colloidal Quantum Dot Ligand Exchange by X-ray Photoelectron Spectroscopy

Science.gov (United States)

Atewologun, Ayomide; Ge, Wangyao; Stiff-Roberts, Adrienne D.

2013-05-01

Colloidal quantum dots (CQDs) are chemically synthesized semiconductor nanoparticles with size-dependent wavelength tunability. Chemical synthesis of CQDs involves the attachment of long organic surface ligands to prevent aggregation; however, these ligands also impede charge transport. Therefore, it is beneficial to exchange longer surface ligands for shorter ones for optoelectronic devices. Typical characterization techniques used to analyze surface ligand exchange include Fourier-transform infrared spectroscopy, x-ray diffraction, transmission electron microscopy, and nuclear magnetic resonance spectroscopy, yet these techniques do not provide a simultaneously direct, quantitative, and sensitive method for evaluating surface ligands on CQDs. In contrast, x-ray photoelectron spectroscopy (XPS) can provide nanoscale sensitivity for quantitative analysis of CQD surface ligand exchange. A unique aspect of this work is that a fingerprint is identified for shorter surface ligands by resolving the regional XPS spectrum corresponding to different types of carbon bonds. In addition, a deposition technique known as resonant infrared matrix-assisted pulsed laser evaporation is used to improve the CQD film uniformity such that stronger XPS signals are obtained, enabling more accurate analysis of the ligand exchange process.

New Hybrid Properties of TiO2 Nanoparticles Surface Modified With Catecholate Type Ligands

Directory of Open Access Journals (Sweden)

Džunuzović Enis

2009-01-01

Full Text Available Abstract Surface modification of nanocrystalline TiO2 particles (45 Å with bidentate benzene derivatives (catechol, pyrogallol, and gallic acid was found to alter optical properties of nanoparticles. The formation of the inner-sphere charge–transfer complexes results in a red shift of the semiconductor absorption compared to unmodified nanocrystallites. The binding structures were investigated by using FTIR spectroscopy. The investigated ligands have the optimal geometry for chelating surface Ti atoms, resulting in ring coordination complexes (catecholate type of binuclear bidentate binding–bridging thus restoring in six-coordinated octahedral geometry of surface Ti atoms. From the Benesi–Hildebrand plot, the stability constants at pH 2 of the order 103 M−1 have been determined.

Improving polymer/nanocrystal hybrid solar cell performance via tuning ligand orientation at CdSe quantum dot surface.

Science.gov (United States)

Fu, Weifei; Wang, Ling; Zhang, Yanfang; Ma, Ruisong; Zuo, Lijian; Mai, Jiangquan; Lau, Tsz-Ki; Du, Shixuan; Lu, Xinhui; Shi, Minmin; Li, Hanying; Chen, Hongzheng

2014-11-12

Achieving superior solar cell performance based on the colloidal nanocrystals remains challenging due to their complex surface composition. Much attention has been devoted to the development of effective surface modification strategies to enhance electronic coupling between the nanocrystals to promote charge carrier transport. Herein, we aim to attach benzenedithiol ligands onto the surface of CdSe nanocrystals in the "face-on" geometry to minimize the nanocrystal-nanocrystal or polymer-nanocrystal distance. Furthermore, the "electroactive" π-orbitals of the benzenedithiol are expected to further enhance the electronic coupling, which facilitates charge carrier dissociation and transport. The electron mobility of CdSe QD films was improved 20 times by tuning the ligand orientation, and high performance poly[2,6-(4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT):CdSe nanocrystal hybrid solar cells were also achieved, showing a highest power conversion efficiency of 4.18%. This research could open up a new pathway to improve further the performance of colloidal nanocrystal based solar cells.

Ligand Access Channels in Cytochrome P450 Enzymes: A Review

Directory of Open Access Journals (Sweden)

Philippe Urban

2018-05-01

Full Text Available Quantitative structure-activity relationships may bring invaluable information on structural elements of both enzymes and substrates that, together, govern substrate specificity. Buried active sites in cytochrome P450 enzymes are connected to the solvent by a network of channels exiting at the distal surface of the protein. This review presents different in silico tools that were developed to uncover such channels in P450 crystal structures. It also lists some of the experimental evidence that actually suggest that these predicted channels might indeed play a critical role in modulating P450 functions. Amino acid residues at the entrance of the channels may participate to a first global ligand recognition of ligands by P450 enzymes before they reach the buried active site. Moreover, different P450 enzymes show different networks of predicted channels. The plasticity of P450 structures is also important to take into account when looking at how channels might play their role.

A Fluid Membrane-Based Soluble Ligand Display System for Live CellAssays

Energy Technology Data Exchange (ETDEWEB)

Nam, Jwa-Min; Nair, Pradeep N.; Neve, Richard M.; Gray, Joe W.; Groves, Jay T.

2005-10-14

Cell communication modulates numerous biological processes including proliferation, apoptosis, motility, invasion and differentiation. Correspondingly, there has been significant interest in the development of surface display strategies for the presentation of signaling molecules to living cells. This effort has primarily focused on naturally surface-bound ligands, such as extracellular matrix components and cell membranes. Soluble ligands (e.g. growth factors and cytokines) play an important role in intercellular communications, and their display in a surface-bound format would be of great utility in the design of array-based live cell assays. Recently, several cell microarray systems that display cDNA, RNAi, or small molecules in a surface array format were proven to be useful in accelerating high-throughput functional genetic studies and screening therapeutic agents. These surface display methods provide a flexible platform for the systematic, combinatorial investigation of genes and small molecules affecting cellular processes and phenotypes of interest. In an analogous sense, it would be an important advance if one could display soluble signaling ligands in a surface assay format that allows for systematic, patterned presentation of soluble ligands to live cells. Such a technique would make it possible to examine cellular phenotypes of interest in a parallel format with soluble signaling ligands as one of the display parameters. Herein we report a ligand-modified fluid supported lipid bilayer (SLB) assay system that can be used to functionally display soluble ligands to cells in situ (Figure 1A). By displaying soluble ligands on a SLB surface, both solution behavior (the ability to become locally enriched by reaction-diffusion processes) and solid behavior (the ability to control the spatial location of the ligands in an open system) could be combined. The method reported herein benefits from the naturally fluid state of the supported membrane, which allows

Catalyst-Free Conjugation and In Situ Quantification of Nanoparticle Ligand Surface Density Using Fluorogenic Cu-Free Click Chemistry

DEFF Research Database (Denmark)

Jølck, Rasmus Irming; Sun, Honghao; Berg, Rolf Henrik

2011-01-01

A highly efficient method for functionalizing nanoparticles and directly quantifying conjugation efficiency and ligand surface density has been developed. Attachment of 3-azido-modifed RGD-peptides to PEGylated liposomes was achieved by using Cu-free click conditions. Upon coupling a fluorophore ...

Electrochemical surface-enhanced Raman scattering measurement on ligand capped PbS quantum dots at gap of Au nanodimer

Science.gov (United States)

Li, Xiaowei; Minamimoto, Hiro; Murakoshi, Kei

2018-05-01

The vibrational characteristics of ligand-capped lead sulfide (PbS) quantum dots (QDs) were clarified via electrochemical surface-enhanced Raman spectroscopy (EC-SERS) using a hybridized system of gold (Au) nanodimers and PbS QDs under electrochemical potential control. Enhanced electromagnetic field caused by the coupling of QDs with plasmonic Au nanodimers allowed the characteristic behavior of the ligand oleic acid (OA) on the PbS QD surface to be detected under electrochemical potential control. Binding modes between the QDs and OA molecules were characterized using synchronous two-dimensional correlation spectra at distinct electrochemical potentials, confirming that the bidentate bridging mode was probably the most stable mode even under relatively negative potential polarization. Changes in binding modes and molecular orientations resulted in fluctuations in EC-SERS spectra. The present observations strongly recommend the validity of the QD-plasmonic nanostructure coupled system for sensitive molecular detection via EC-SERS.

Cell-specific targeting by heterobivalent ligands.

Science.gov (United States)

Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

2011-07-20

Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

A response calculus for immobilized T cell receptor ligands

DEFF Research Database (Denmark)

Andersen, P S; Menné, C; Mariuzza, R A

2001-01-01

determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated...

iview: an interactive WebGL visualizer for protein-ligand complex.

Science.gov (United States)

Li, Hongjian; Leung, Kwong-Sak; Nakane, Takanori; Wong, Man-Hon

2014-02-25

Visualization of protein-ligand complex plays an important role in elaborating protein-ligand interactions and aiding novel drug design. Most existing web visualizers either rely on slow software rendering, or lack virtual reality support. The vital feature of macromolecular surface construction is also unavailable. We have developed iview, an easy-to-use interactive WebGL visualizer of protein-ligand complex. It exploits hardware acceleration rather than software rendering. It features three special effects in virtual reality settings, namely anaglyph, parallax barrier and oculus rift, resulting in visually appealing identification of intermolecular interactions. It supports four surface representations including Van der Waals surface, solvent excluded surface, solvent accessible surface and molecular surface. Moreover, based on the feature-rich version of iview, we have also developed a neat and tailor-made version specifically for our istar web platform for protein-ligand docking purpose. This demonstrates the excellent portability of iview. Using innovative 3D techniques, we provide a user friendly visualizer that is not intended to compete with professional visualizers, but to enable easy accessibility and platform independence.

The Effect of Nitrogen Surface Ligands on Propane Metathesis: Design and Characterizations of N-modified SBA15-Supported Schrock-type Tungsten Alkylidyne

KAUST Repository

Eid, Ahmed A.

2014-04-01

Catalysis, which is primarily a molecular phenomenon, is an important field of chemistry because it requires the chemical conversion of molecules into other molecules. It also has an effect on many fields, including, but not limited to, industry, environment and life Science[1]. Surface Organometallic Chemistry is an effective methodology for Catalysis as it imports the concept and mechanism of organometallic chemistry, to surface science and heterogeneous catalysis. So, it bridges the gap between homogenous and heterogeneous catalysis[1]. The aim of the present research work is to study the effect of Nitrogen surface ligands on the activity of Alkane, Propane in particular, metathesis. Our approach is based on the preparation of selectively well-defined group (VI) transition metal complexes supported onto mesoporous materials, SBA15 and bearing amido and/or imido ligands. We choose nitrogen ligands because, according to the literature, they showed in some cases better catalytic properties in homogenous catalysis in comparison with their oxygen counterparts[2]. The first section covers the modification of a highly dehydroxylated SBA15 surface using a controlled ammonia treatment. These will result in the preparation of two kind of Nitrogen surface ligands: -\\tOne with vicinal silylamine/silanol, (≡SiNH2)(≡SiOH), noted [N,O]SBA15 and, -\\tAnother\\tone\\twith\\tvicinal\\tbis-silylamine moieties (≡SiNH2)2, noted [N,N]SBA15[3]. The second section covers the reaction of Schrock type Tungsten Carbyne [W(≡C- tBu)(CH2-tBu)3] with those N-surface ligands and their characterizations by FT-IR, multiple quantum solid state NMR (1H, 13C), elemental analysis and gas phase analysis. The third section covers the generation of the active site, tungsten hydride species. Their performance toward propane metathesis reaction using the dynamic reactor technique PID compared toward previous well-known catalysts supported on silica oxide or mesoporous materials[4]. A fairly good

The role of surface ligands in quantum-dot devices: Villain or unsung hero?

Energy Technology Data Exchange (ETDEWEB)

Pietryga, Jeffrey Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2018-02-20

For over three decades, the study of nanocrystal quantum dots (QDs), which are solution-synthesized nanometer-scale bits of semiconductor materials, has produced singular advances in both our understanding of quantum confinement effects, and in our ability to make use of them in tech-relevant materials. Accordingly, QDs have found their way into the marketplace, specifically as high-performance fluorophores for, e.g., displays and biolabeling. In such applications, optimization of the QD surface, including the passivating ligands, is key to keeping photo-excited carriers from leaving the QD interior before recombining, resulting in a high fluorescence efficiency. Increasingly, attention has turned to realize the promise of QDs for optoelectronic applications (e.g., solar cells, LEDs, sensors) which require charge carriers to controllably enter, exit and/or travel through QDs, a much more challenging problem. In this scenario, the role of the QD surface must be completely reimagined, from being an impenetrable wall to being a gateway, or even a ramp. In this talk, I’ll explore the inherent contrast between QD fluorophore and device applications, and describe how ligands, originally thought only to be impediments to QD electronic devices, may actually give the savvy QD device designer control over function and performance in a manner unknown in bulk semiconductor devices. Finally, I’ll survey recent efforts at Los Alamos to develop a universal tool box for deposition of conductive QD films that may finally allow the manufacturing of economical, high-performance devices for a wide range of applications.

Cavity-ligand binding in a simple two-dimensional water model

Directory of Open Access Journals (Sweden)

G. Mazovec

2016-02-01

Full Text Available By means of Monte Carlo computer simulations in the isothermal-isobaric ensemble, we investigated the interaction of a hydrophobic ligand with the hydrophobic surfaces of various curvatures (planar, convex and concave. A simple two-dimensional model of water, hydrophobic ligand and surface was used. Hydration/dehidration phenomena concerning water molecules confined close to the molecular surface were investigated. A notable dewetting of the hydrophobic surfaces was observed together with the reorientation of the water molecules close to the surface. The hydrogen bonding network was formed to accommodate cavities next to the surfaces as well as beyond the first hydration shell. The effects were most strongly pronounced in the case of concave surfaces having large curvature. This simplified model can be further used to evaluate the thermodynamic fingerprint of the docking of hydrophobic ligands.

Surface ligands affect photoinduced modulation of the quantum dots optical performance

Science.gov (United States)

Krivenkov, Victor A.; Samokhvalov, Pavel S.; Linkov, Pavel A.; Solovyeva, Daria O.; Kotkovskii, Gennadii E.; Chistyakov, Alexander A.; Nabiev, Igor

2014-05-01

Changes of optical properties of the solutions of CdSe/ZnS quantum dots (QDs) covered with the trioctylphosphine oxide (TOPO) ligands under the pulsed ultraviolet (UV) laser irradiation are observed. The fluorescence quantum yield (QY) of QDs decreases by more than an order of magnitude when the radiation dose approaches 2 × 10-15 J per particle. This process is accompanied by a blue shift of both fluorescence and the first excitonic absorption peaks. The fluorescence quenching becomes less pronounced when the overall TOPO content in the solution is increased. When ТОРО ligands are replaced with n-hexadecylamine (HDA), QY and spectral properties are not changed at the same irradiation conditions. We assume that the above changes of the optical properties are associated with photooxidation of TOPO ligands by excited QD. Such process is less probable for the HDA ligand due to its different energy structure.

Tuning optoelectronic properties of small semiconductor nanocrystals through surface ligand chemistry

Science.gov (United States)

Lawrence, Katie N.

, can increase the stability of SNCs during solution-phase electrochemical characterization. Therefore, we utilized these properties to characterize solution-state electrochemical properties and photocatalytic activity of ternary copper indium diselenide (CuInSe2) SNCs as a function of their size and surface ligand chemistry. Electrochemical characterization of our PEG-thiolate-coated SNCs showed that the thermodynamic driving force (-?G) for oxygen reduction, which increased with decreasing bandgap, was a major contributor to the overall photocatalytic reaction. Additionally, phenol degradation efficiency was monitored in which the smallest diameter SNC and shortest chain length of PEG provided the highest efficiency. The information provided herein could be used to produce superior SNC photocatalysts for a variety of applications including oxidation of organic contaminants, conversion of water to hydrogen gas, and decomposition of crude oil or pesticides. Therefore, we believe our work will significantly advance quantitative electrochemical characterization of SNCs and allow for the design of highly efficient, sustainable photocatalysts resulting in economic and environmental benefits.

O-fucosylation of the notch ligand mDLL1 by POFUT1 is dispensable for ligand function.

Directory of Open Access Journals (Sweden)

Julia Müller

Full Text Available Fucosylation of Epidermal Growth Factor-like (EGF repeats by protein O-fucosyltransferase 1 (POFUT1 in vertebrates, OFUT1 in Drosophila is pivotal for NOTCH function. In Drosophila OFUT1 also acts as chaperone for Notch independent from its enzymatic activity. NOTCH ligands are also substrates for POFUT1, but in Drosophila OFUT1 is not essential for ligand function. In vertebrates the significance of POFUT1 for ligand function and subcellular localization is unclear. Here, we analyze the importance of O-fucosylation and POFUT1 for the mouse NOTCH ligand Delta-like 1 (DLL1. We show by mass spectral glycoproteomic analyses that DLL1 is O-fucosylated at the consensus motif C²XXXX(S/TC³ (where C² and C³ are the second and third conserved cysteines within the EGF repeats found in EGF repeats 3, 4, 7 and 8. A putative site with only three amino acids between the second cysteine and the hydroxy amino acid within EGF repeat 2 is not modified. DLL1 proteins with mutated O-fucosylation sites reach the cell surface and accumulate intracellularly. Likewise, in presomitic mesoderm cells of POFUT1 deficient embryos DLL1 is present on the cell surface, and in mouse embryonic fibroblasts lacking POFUT1 the same relative amount of overexpressed wild type DLL1 reaches the cell surface as in wild type embryonic fibroblasts. DLL1 expressed in POFUT1 mutant cells can activate NOTCH, indicating that POFUT1 is not required for DLL1 function as a Notch ligand.

Ligand-induced association of surface immunoglobulin with the detergent insoluble cytoskeleton may involve an 89K protein

International Nuclear Information System (INIS)

Gupta, S.K.; Woda, B.

1986-01-01

Membrane immunoglobulin of B-lymphocytes is thought to play an important role in antigen recognition and cellular activation. Binding of cross-linking ligands to surface immunoglobulin (SIg) on intact cells converts it to a detergent insoluble state, and this conversion is associated with the transmission of a mitogenic signal. Insolubilized membrane proteins may be solubilized by incubating the detergent insoluble cytoskeletons in buffers which convert F-actin to G-actin [(Buffer 1), 0.34M sucrose, 0.5mM ATP, 0.5mM Dithiothrietol and lmM EDTA]. Immunoprecipitation of SIg from the detergent soluble fraction of 35 S-methionine labeled non ligand treated rat B-cells results in the co-isolation of an 89K protein and a 44K protein, presumably actin. The 89K protein is not associated with the fraction of endogenous detergent insoluble SIg. On treatment of rat B cells with cross-linking ligand (anti-Ig) the 89K protein becomes detergent insoluble along with most of the SIg and co-isolates with SIg on immunoprecipitation of the detergent insoluble, buffer l solubilized fraction. The migration of the SIg-associated 89K protein from the detergent soluble fraction to the detergent insoluble fraction after ligand treatment, suggests that this protein might be involved in linking SIg to the underlying cytoskeleton and could be involved in the transmission of a mitogenic signal

CO2 activation through silylimido and silylamido zirconium hydrides supported on N-donor chelating SBA15 surface ligand

KAUST Repository

Pasha, Fahran Ahmad; Bendjeriou-Sedjerari, Anissa; Abou-Hamad, Edy; Huang, Kuo-Wei; Basset, Jean-Marie

2016-01-01

Density functional theory calculations and 2D 1H-13C HETCOR solid state NMR spectroscopy prove that CO2 can probe, by its own reactivity, different types of N-donor surface ligands on SBA15-supported ZrIV hydrides: [(≡Si-O-)(≡Si-N=)[Zr]H] and [(≡Si

Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans.

Science.gov (United States)

Motola, Daniel L; Cummins, Carolyn L; Rottiers, Veerle; Sharma, Kamalesh K; Li, Tingting; Li, Yong; Suino-Powell, Kelly; Xu, H Eric; Auchus, Richard J; Antebi, Adam; Mangelsdorf, David J

2006-03-24

In response to environmental and dietary cues, the C. elegans orphan nuclear receptor, DAF-12, regulates dauer diapause, reproductive development, fat metabolism, and life span. Despite strong evidence for hormonal control, the identification of the DAF-12 ligand has remained elusive. In this work, we identified two distinct 3-keto-cholestenoic acid metabolites of DAF-9, a cytochrome P450 involved in hormone production, that function as ligands for DAF-12. At nanomolar concentrations, these steroidal ligands (called dafachronic acids) bind and transactivate DAF-12 and rescue the hormone deficiency of daf-9 mutants. Interestingly, DAF-9 has a biochemical activity similar to mammalian CYP27A1 catalyzing addition of a terminal acid to the side chain of sterol metabolites. Together, these results define the first steroid hormones in nematodes as ligands for an invertebrate orphan nuclear receptor and demonstrate that steroidal regulation of reproduction, from biology to molecular mechanism, is conserved from worms to humans.

Ligand substitution and selective surface coordination studies of iodine and 2,5-dihydroxythiophenol at platinum electrodes

International Nuclear Information System (INIS)

Berry, G.M.; Soriaga, M.P.

1989-01-01

The relative surface coordination strengths of 2,5-dihydroxythiophenol (DHT) and iodine at a smooth polycrystalline platinum electrode have been investigated by thin-layer electrochemical techniques. The competitive chemisorption was studied by exposing the Pt electrode to solutions of varying mole fractions of I and DHT. Studies of ligand substitution were carried out by the introduction of an iodine-coated Pt electrode into DHT solutions, and the introduction of a DHT-coated into I solutions. Surface coverage measurements indicated that DHT is preferentially adsorbed and will displace chemisorbed iodine at the Pt electrode. Chemisorbed DHT is not appreciably displaced by iodine. These results and their contribution to the trend in the selective surface coordination chemistry of platinum electrodes will be discussed

Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal.

Science.gov (United States)

Yan, Kelley S; Janda, Claudia Y; Chang, Junlei; Zheng, Grace X Y; Larkin, Kathryn A; Luca, Vincent C; Chia, Luis A; Mah, Amanda T; Han, Arnold; Terry, Jessica M; Ootani, Akifumi; Roelf, Kelly; Lee, Mark; Yuan, Jenny; Li, Xiao; Bolen, Christopher R; Wilhelmy, Julie; Davies, Paige S; Ueno, Hiroo; von Furstenberg, Richard J; Belgrader, Phillip; Ziraldo, Solongo B; Ordonez, Heather; Henning, Susan J; Wong, Melissa H; Snyder, Michael P; Weissman, Irving L; Hsueh, Aaron J; Mikkelsen, Tarjei S; Garcia, K Christopher; Kuo, Calvin J

2017-05-11

The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands. For example, individual mutations in Wnt ligands have not revealed homeostatic phenotypes in the intestinal epithelium-an archetypal canonical, Wnt pathway-dependent, rapidly self-renewing tissue, the regeneration of which is fueled by proliferative crypt Lgr5 + intestinal stem cells (ISCs). R-spondin ligands (RSPO1-RSPO4) engage distinct LGR4-LGR6, RNF43 and ZNRF3 receptor classes, markedly potentiate canonical Wnt/β-catenin signalling, and induce intestinal organoid growth in vitro and Lgr5 + ISCs in vivo. However, the interchangeability, functional cooperation and relative contributions of Wnt versus RSPO ligands to in vivo canonical Wnt signalling and ISC biology remain unknown. Here we identify the functional roles of Wnt and RSPO ligands in the intestinal crypt stem-cell niche. We show that the default fate of Lgr5 + ISCs is to differentiate, unless both RSPO and Wnt ligands are present. However, gain-of-function studies using RSPO ligands and a new non-lipidated Wnt analogue reveal that these ligands have qualitatively distinct, non-interchangeable roles in ISCs. Wnt proteins are unable to induce Lgr5 + ISC self-renewal, but instead confer a basal competency by maintaining RSPO receptor expression that enables RSPO ligands to actively drive and specify the extent of stem-cell expansion. This functionally non-equivalent yet cooperative interaction

New Ru(II) Complexes for Dual Photoreactivity: Ligand Exchange and 1O2 Generation

OpenAIRE

Knoll, Jessica D.; Albani, Bryan A.; Turro, Claudia

2015-01-01

Uncovering the factors that govern the electronic structure of Ru(II)–polypyridyl complexes is critical in designing new compounds for desired photochemical reactions, and strategies to tune excited states for ligand dissociation and 1O2 production are discussed herein. The generally accepted mechanism for photoinduced ligand dissociation proposes that population of the dissociative triplet ligand field (3LF) state proceeds through thermal population from the vibrationally cooled triplet meta...

Surface-initiated addition polymerization of norbornene by a Pd(II) catalyst bearing acetylacetone ligand on the glass slide

Science.gov (United States)

He, Xiaohui; Wang, Kaiti; Chen, Yiwang; Yuan, Bin

2012-02-01

A Pd catalyst bearing acetylacetone ligand [(CH3CO)2CHPdCl2] was covalently attracted onto the surface of glass slides, and then these Pd-terminated glass slides were immersed into a toluene solution of norbornene (NB) to produce a vinyl-type addition polynorbornene (PNB) layer on the surface of glass slides. It was found that the contract angles of the PNB-terminated glass slides surface increased with the increasing of polymerization time, and the thickness of the PNB layers were approximately 0-44.0 μm when the polymerization time was 0.5-24 h. The researching on etching also has been operated.

Basigin-2 Is a Cell Surface Receptor for Soluble Basigin Ligand*S⃞

Science.gov (United States)

Belton, Robert J.; Chen, Li; Mesquita, Fernando S.; Nowak, Romana A.

2008-01-01

The metastatic spread of a tumor is dependent upon the ability of the tumor to stimulate surrounding stromal cells to express enzymes required for tissue remodeling. The immunoglobulin superfamily protein basigin (EMMPRIN/CD147) is a cell surface glycoprotein expressed by tumor cells that stimulates matrix metalloproteinase and vascular endothelial growth factor expression in stromal cells. The ability of basigin to stimulate expression of molecules involved in tissue remodeling and angiogenesis makes basigin a potential target for the development of strategies to block metastasis. However, the identity of the cell surface receptor for basigin remains controversial. The goal of this study was to determine the identity of the receptor for basigin. Using a novel recombinant basigin protein (rBSG) corresponding to the extracellular domain of basigin, it was demonstrated that the native, nonglycosylated rBSG protein forms dimers in solution. Furthermore, rBSG binds to the surface of uterine fibroblasts, activates the ERK1/2 signaling pathway, and induces expression of matrix metalloproteinases 1, 2, and 3. Proteins that interact with rBSG were isolated using a biotin label transfer technique and sequenced by matrix-assisted laser desorption ionization tandem mass spectrophotometry. The results demonstrate that rBSG interacts with basigin expressed on the surface of fibroblasts and is subsequently internalized. During internalization, rBSG associates with a novel form of human basigin (basigin-3). It was concluded that cell surface basigin functions as a membrane receptor for soluble basigin and this homophilic interaction is not dependent upon glycosylation of the basigin ligand. PMID:18434307

Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for specific ligand inhibition.

Directory of Open Access Journals (Sweden)

Matthew W Parker

Full Text Available Neuropilin (Nrp receptors function as essential cell surface receptors for the Vascular Endothelial Growth Factor (VEGF family of proangiogenic cytokines and the semaphorin 3 (Sema3 family of axon guidance molecules. There are two Nrp homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A(164/5 isoform, which is essential for developmental angiogenesis. We demonstrate that VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further, we show that Sema3F does not display the Nrp-specific binding to the b1 domain seen with VEGF-A. Engineered soluble Nrp receptor fragments that selectively sequester ligands from the active signaling complex are an attractive modality for selectively blocking the angiogenic and chemorepulsive functions of Nrp ligands. Utilizing the information on Nrp ligand binding specificity, we demonstrate Nrp constructs that specifically sequester Sema3 in the presence of VEGF-A. This establishes that unique mechanisms are used by Nrp receptors to mediate specific ligand binding and that these differences can be exploited to engineer soluble Nrp receptors with specificity for Sema3.

Colloidal-quantum-dot photovoltaics using atomic-ligand passivation

KAUST Repository

Tang, Jiang

2011-09-18

Colloidal-quantum-dot (CQD) optoelectronics offer a compelling combination of solution processing and spectral tunability through quantum size effects. So far, CQD solar cells have relied on the use of organic ligands to passivate the surface of the semiconductor nanoparticles. Although inorganic metal chalcogenide ligands have led to record electronic transport parameters in CQD films, no photovoltaic device has been reported based on such compounds. Here we establish an atomic ligand strategy that makes use of monovalent halide anions to enhance electronic transport and successfully passivate surface defects in PbS CQD films. Both time-resolved infrared spectroscopy and transient device characterization indicate that the scheme leads to a shallower trap state distribution than the best organic ligands. Solar cells fabricated following this strategy show up to 6% solar AM1.5G power-conversion efficiency. The CQD films are deposited at room temperature and under ambient atmosphere, rendering the process amenable to low-cost, roll-by-roll fabrication. © 2011 Macmillan Publishers Limited. All rights reserved.

General Linker Diversification Approach to Bivalent Ligand Assembly: Generation of an Array of Ligands for the Cation-Independent Mannose 6-Phosphate Receptor.

Science.gov (United States)

Fei, Xiang; Zavorka, Megan E; Malik, Guillaume; Connelly, Christopher M; MacDonald, Richard G; Berkowitz, David B

2017-08-18

A generalized strategy is presented for the rapid assembly of a set of bivalent ligands with a variety of linking functionalities from a common monomer. Herein, an array of phosphatase-inert mannose-6-phosphonate-presenting ligands for the cation-independent-mannose 6-phosphate receptor (CI-MPR) is constructed. Receptor binding affinity varies with linking functionality-the simple amide and 1,5-triazole(tetrazole) being preferred over the 1,4-triazole. This approach is expected to find application across chemical biology, particularly in glycoscience, wherein multivalency often governs molecular recognition.

Surfactant Ligand Removal and Rational Fabrication of Inorganically Connected Quantum Dots

KAUST Repository

Zhang, Haitao

2011-12-14

A novel method is reported to create inorganically connected nanocrystal (NC) assemblies for both II-VI and IV-VI semiconductors by removing surfactant ligands using (NH 4) 2S. This surface modification process differs from ligand exchange methods in that no new surfactant ligands are introduced and the post-treated NC surfaces are nearly bare. The detailed mechanism study shows that the high reactivity between (NH 4) 2S and metal-surfactant ligand complexes enables the complete removal of surfactant ligands in seconds and converts the NC metal-rich shells into metal sulfides. The post-treated NCs are connected through metal-sulfide bonding and form a larger NCs film assembly, while still maintaining quantum confinement. Such "connected but confined" NC assemblies are promising new materials for electronic and optoelectronic devices. © 2011 American Chemical Society.

Synthesis of freestanding water-soluble indium oxide nanocrystals capped by alanine nitric acid via ligand exchange for thin film transistors and effects of ligands on the electrical properties

International Nuclear Information System (INIS)

Choi, Jin-Kyu; Koh, Ye-Seul; Jeong, Hyun-Dam

2015-01-01

We demonstrate synthesis of freestanding water-soluble indium oxide nanocrystals (In 2 O 3 NCs) by ligand exchange to β-alanine nitric acid (Ala·HNO 3 ) and its application for active channel layer in thin film transistors (TFTs), with investigation of the effect of curing temperatures on the TFT properties in terms of thermal behaviour of the ligand molecules at 150, 300, and 350 °C. After ligand exchange from long alkyl ligand (myristic acid, MA) to short Ala·HNO 3 , the mobility of NC TFTs cured at 150 °C increased by over 1 order of magnitude, from 1.3 × 10 −4 cm 2 V -1 s −1 to 4.5 × 10 −3 cm 2 V -1 s −1 , due to enhanced tunnelling rate (Γ) between adjective NCs. Higher curing temperatures such as 300 and 350 °C, inducing thermal decomposition of the organic ligands, led to further enhancement of the mobility, particularly up to 2.2 cm 2 V -1 s −1 for the In 2 O 3 NC-Ala·HNO 3 TFT cured at 350 °C. It is also found that the ligand exchange of In 2 O 3 NC in acidic condition (e.g. HNO 3 ) would be simple and effective to reduce the surface defects by surface etching, which may lead to better device performances. - Graphical abstract: Display Omitted - Highlights: • Freestanding water-soluble In 2 O 3 nanocrystals (NCs) were synthesized by ligand exchange. • Thin film transistors (TFTs) of colloidal NCs were fabricated by spin-coating method. • Water-soluble In 2 O 3 NC TFTs showed higher mobilities due to shorter ligand length. • Surface defects of NCs were notably reduced by surface etching during ligand exchange

Distinct Iron-binding Ligands in the Upper Water Column at Station ALOHA

Science.gov (United States)

Bundy, R.; Boiteau, R.; Repeta, D.

2016-02-01

The distribution and chemical properties of iron-binding organic ligands at station ALOHA were examined using a combination of solid phase extraction (SPE) followed by high pressure liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). HPLC-ICPMS ligand measurements were complemented by competitive ligand exchange adsorptive cathodic stripping voltammetry (CLE-ACSV) analysis using salicylaldoxime as the added ligand. By HPLC-ICPMS, we find enhanced concentrations of distinct naturally-occurring polar iron-binding ligands present at the surface and in the chlorophyll maximum. Lower concentrations were found in the subsurface, where a suite of non-polar ligands was detected. Siderophores were present at the deepest depths sampled at station ALOHA, down to 400m. Incubation studies provided evidence for the production of iron-binding ligands associated with nutrient amended phytoplankton growth in surface waters, and as a result of microbial particle remineralization in the subsurface water column. Ligands classes identified via SPE were then compared to CLE-ACSV ligand measurements, as well as the conditional stability constants measured from model polar and non-polar siderophores, yielding insight to the sources of iron-binding ligands throughout the water column at station ALOHA.

Wnt ligands from the embryonic surface ectoderm regulate ‘bimetallic strip’ optic cup morphogenesis in mouse

Science.gov (United States)

Carpenter, April C.; Smith, April N.; Wagner, Heidi; Cohen-Tayar, Yamit; Rao, Sujata; Wallace, Valerie; Ashery-Padan, Ruth; Lang, Richard A.

2015-01-01

The Wnt/β-catenin response pathway is central to many developmental processes. Here, we assessed the role of Wnt signaling in early eye development using the mouse as a model system. We showed that the surface ectoderm region that includes the lens placode expressed 12 out of 19 possible Wnt ligands. When these activities were suppressed by conditional deletion of wntless (Le-cre; Wlsfl/fl) there were dramatic consequences that included a saucer-shaped optic cup, ventral coloboma, and a deficiency of periocular mesenchyme. This phenotype shared features with that produced when the Wnt/β-catenin pathway co-receptor Lrp6 is mutated or when retinoic acid (RA) signaling in the eye is compromised. Consistent with this, microarray and cell fate marker analysis identified a series of expression changes in genes known to be regulated by RA or by the Wnt/β-catenin pathway. Using pathway reporters, we showed that Wnt ligands from the surface ectoderm directly or indirectly elicit a Wnt/β-catenin response in retinal pigment epithelium (RPE) progenitors near the optic cup rim. In Le-cre; Wlsfl/fl mice, the numbers of RPE cells are reduced and this can explain, using the principle of the bimetallic strip, the curvature of the optic cup. These data thus establish a novel hypothesis to explain how differential cell numbers in a bilayered epithelium can lead to shape change. PMID:25715397

Mechanism of charge transport in ligand-capped crystalline CdTe nanoparticles according to surface photovoltaic and photoacoustic results

Energy Technology Data Exchange (ETDEWEB)

Li Kuiying, E-mail: kuiyingli@ysu.edu.cn [National Laboratory of Metastable Materials Manufacture Technology and Science, Yanshan University, Hebei Str. 438, Qinhuangdao, Hebei Province 066004 (China); Zhang Hao [Key Laboratory for Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012 (China); Yang Weiyong; Wei Sailing [National Laboratory of Metastable Materials Manufacture Technology and Science, Yanshan University, Hebei Str. 438, Qinhuangdao, Hebei Province 066004 (China); Wang Dayang, E-mail: dayang@mpikg-golm.mpg.de [Max Planck Institute of Colloids and Interfaces, Potsdam 14424 (Germany)

2010-09-01

By combining surface photovoltaic and photoacoustic techniques, we probed the photogenerated charge transport channels of 3-mercaptopropionic acid (MPA)- and 2-mercaptoethylamine (MA)-capped crystalline CdTe nanoparticles on illumination with UV-near IR light. The results experimentally confirmed the presence of a CdS shell outside the CdTe core that formed through the self-assembly and decomposition of mercapto ligands during CdTe preparation. The data revealed that the CdS layer was partly responsible for the deexcitation behavior of the photogenerated carriers, which is related to the quantum tunnel effect. Experiments demonstrated that two quantum wells were located at wavelengths of 440 and 500 nm in buried interfacial space-charge regions, whereas the formation of a ligand layer obstructed charge transfer transitions of the core CdTe nanoparticles to a certain extent.

Engineering bacterial surface displayed human norovirus capsid proteins: A novel system to explore interaction between norovirus and ligands

Directory of Open Access Journals (Sweden)

Mengya eNiu

2015-12-01

Full Text Available Human noroviruses (HuNoVs are major contributors to acute nonbacterial gastroenteritis outbreaks. Many aspects of HuNoVs are poorly understood due to both the current inability to culture HuNoVs, and the lack of efficient small animal models. Surrogates for HuNoVs, such as recombinant viral like particles (VLPs expressed in eukaryotic system or P particles expressed in prokaryotic system, have been used for studies in immunology and interaction between the virus and its receptors. However, it is difficult to use VLPs or P particles to collect or isolate potential ligands binding to these recombinant capsid proteins. In this study, a new strategy was used to collect HuNoVs binding ligands through the use of ice nucleation protein (INP to display recombinant capsid proteins of HuNoVs on bacterial surfaces. The viral protein-ligand complex could be easily separated by a low speed centrifugation step. This system was also used to explore interaction between recombinant capsid proteins of HuNoVs and their receptors. In this system, the VP1 capsid encoding gene (ORF2 and the protruding domain (P domain encoding gene (3’ terminal fragment of ORF2 of HuNoVs GI.1 and GII.4 were fused with 5’ terminal fragment of ice nucleation protein encoding gene (inaQn. The results demonstrated that the recombinant VP1 and P domains of HuNoVs were expressed and anchored on the surface of Escherichia coli BL21 cells after the bacteria were transformed with the corresponding plasmids. Both cell surface displayed VP1 and P domains could be recognized by HuNoVs specific antibodies and interact with the viral histo-blood group antigens receptors. In both cases, displayed P domains had better binding abilities than VP1. This new strategy of using displayed HuNoVs capsid proteins on the bacterial surface could be utilized to separate HuNoVs binding components from complex samples, to investigate interaction between the virus and its receptors, as well as to develop an

Oxidation of ligand-protected aluminum clusters: An ab initio molecular dynamics study

International Nuclear Information System (INIS)

Alnemrat, Sufian; Hooper, Joseph P.

2014-01-01

We report Car-Parrinello molecular dynamics simulations of the oxidation of ligand-protected aluminum clusters that form a prototypical cluster-assembled material. These clusters contain a small aluminum core surrounded by a monolayer of organic ligand. The aromatic cyclopentadienyl ligands form a strong bond with surface Al atoms, giving rise to an organometallic cluster that crystallizes into a low-symmetry solid and is briefly stable in air before oxidizing. Our calculations of isolated aluminum/cyclopentadienyl clusters reacting with oxygen show minimal reaction between the ligand and O 2 molecules at simulation temperatures of 500 and 1000 K. In all cases, the reaction pathway involves O 2 diffusing through the ligand barrier, splitting into atomic oxygen upon contact with the aluminum, and forming an oxide cluster with aluminum/ligand bonds still largely intact. Loss of individual aluminum-ligand units, as expected from unimolecular decomposition calculations, is not observed except following significant oxidation. These calculations highlight the role of the ligand in providing a steric barrier against oxidizers and in maintaining the large aluminum surface area of the solid-state cluster material

Effects of charge and surface ligand properties of nanoparticles on oxidative stress and gene expression within the gut of Daphnia magna

Energy Technology Data Exchange (ETDEWEB)

Dominguez, Gustavo A.; Lohse, Samuel E.; Torelli, Marco; Murphy, Catherine; Hamers, Robert J.; Orr, Galya; Klaper, Rebecca D.

2015-05-01

Concern has been raised regarding the current and future release of engineered nanomaterials into aquatic environments from industry and other sources. However, not all nanomaterials may cause an environ-mental impact and identifying which nanomaterials may be of greatest concern has been difficult. It is thought that the surface groups of a functionalized nanoparticles (NPs) may play a significant role in determining their interactions with aquatic organisms, but the way in which surface properties of NPs impact their toxicity in whole organisms has been minimally explored. A major point of interaction of NPs with aquatic organisms is in the gastrointestinal tract as they ingest particulates from the water column or from the sediment. The main goal of this study was to use model gold NP (AuNPs) to evaluate the potential effects of the different surfaces groups on NPs on the gut of an aquatic model organism, Daphnia magna. In this study, we exposed daphnids to a range of AuNPs concentrations and assessed the impact of AuNP exposure in the daphnid gut by measuring reactive oxygen species (ROS) production and expression of genes associated with oxidative stress and general cellular stress: glutathione S-transferase(gst), catalase (cat), heat shock protein 70 (hsp70), and metallothionein1 (mt1). We found ROS formation and gene expression were impacted by both charge and the specific surface ligand used. We detected some degree of ROS production in all NP exposures, but positively charged AuNPs induced a greater ROS response. Similarly, we observed that, compared to controls, both positively charged AuNPs and only one negatively AuNP impacted expression of genes associated with cellular stress. Finally, ligand-AuNP exposures showed a different toxicity and gene expression profile than the ligand alone, indicating a NP specific effect.

Ligand-mediated adhesive mechanics of two static, deformed spheres.

Science.gov (United States)

Sircar, Sarthok; Nguyen, Giang; Kotousov, Andrei; Roberts, Anthony J

2016-10-01

A self-consistent model is developed to investigate attachment/detachment kinetics of two static, deformable microspheres with irregular surface and coated with flexible binding ligands. The model highlights how the microscale binding kinetics of these ligands as well as the attractive/repulsive potential of the charged surface affects the macroscale static deformed configuration of the spheres. It is shown that in the limit of smooth, neutrally charged surface (i.e., the dimensionless inverse Debye length, [Formula: see text]), interacting via elastic binders (i.e., the dimensionless stiffness coefficient, [Formula: see text]) the adhesion mechanics approaches the regime of application of the JKR theory, and in this particular limit, the contact radius, R c , scales with the particle radius, R, according to the scaling law, [Formula: see text]. We show that static, deformed, highly charged, ligand-coated surface of micro-spheres exhibit strong adhesion. Normal stress distribution within the contact area adjusts with the binder stiffness coefficient, from a maximum at the center to a maximum at the periphery of the region. Although reported in some in vitro experiments involving particle adhesion, until now a physical interpretation for this variation of the stress distribution for deformable, charged, ligand-coated microspheres is missing. Surface roughness results in a diminished adhesion with a distinct reduction in the pull-off force, larger separation gap, weaker normal stress and limited area of adhesion. These results are in agreement with the published experimental findings.

Autocrine signal transmission with extracellular ligand degradation

Science.gov (United States)

Muratov, C B; Posta, F; Shvartsman, S Y

2009-03-01

Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers.

The utilization of BSA-modified chip on the investigation of ligand ...

African Journals Online (AJOL)

Administrator

2009-12-15

Dec 15, 2009 ... investigation of ligand/protein interaction with surface plasma resonance ... for immobilizing proteins or low-molecular-weight ligands to dextran ..... contamination in dynamic aqueous environments using optical sensors. Anal.

Characterization of SynCAM surface trafficking using a SynCAM derived ligand with high homophilic binding affinity

International Nuclear Information System (INIS)

Breillat, Christelle; Thoumine, Olivier; Choquet, Daniel

2007-01-01

In order to better probe SynCAM function in neurons, we produced a fusion protein between the extracellular domain of SynCAM1 and the constant fragment of human IgG (SynCAM-Fc). Whether in soluble form or immobilized on latex microspheres, the chimera bound specifically to the surface of hippocampal neurons and recruited endogenous SynCAM molecules. SynCAM-Fc was also used in combination with Quantum Dots to follow the mobility of transfected SynCAM receptors at the neuronal surface. Both immobile and highly mobile SynCAM were found. Thus, SynCAM-Fc behaves as a high affinity ligand that can be used to study the function of SynCAM at the neuronal membrane

Synthesis of freestanding water-soluble indium oxide nanocrystals capped by alanine nitric acid via ligand exchange for thin film transistors and effects of ligands on the electrical properties

Energy Technology Data Exchange (ETDEWEB)

Choi, Jin-Kyu; Koh, Ye-Seul; Jeong, Hyun-Dam, E-mail: hdjeong@chonnam.ac.kr

2015-07-15

We demonstrate synthesis of freestanding water-soluble indium oxide nanocrystals (In{sub 2}O{sub 3} NCs) by ligand exchange to β-alanine nitric acid (Ala·HNO{sub 3}) and its application for active channel layer in thin film transistors (TFTs), with investigation of the effect of curing temperatures on the TFT properties in terms of thermal behaviour of the ligand molecules at 150, 300, and 350 °C. After ligand exchange from long alkyl ligand (myristic acid, MA) to short Ala·HNO{sub 3}, the mobility of NC TFTs cured at 150 °C increased by over 1 order of magnitude, from 1.3 × 10{sup −4} cm{sup 2}V{sup -1}s{sup −1} to 4.5 × 10{sup −3} cm{sup 2}V{sup -1}s{sup −1}, due to enhanced tunnelling rate (Γ) between adjective NCs. Higher curing temperatures such as 300 and 350 °C, inducing thermal decomposition of the organic ligands, led to further enhancement of the mobility, particularly up to 2.2 cm{sup 2}V{sup -1}s{sup −1} for the In{sub 2}O{sub 3} NC-Ala·HNO{sub 3} TFT cured at 350 °C. It is also found that the ligand exchange of In{sub 2}O{sub 3} NC in acidic condition (e.g. HNO{sub 3}) would be simple and effective to reduce the surface defects by surface etching, which may lead to better device performances. - Graphical abstract: Display Omitted - Highlights: • Freestanding water-soluble In{sub 2}O{sub 3} nanocrystals (NCs) were synthesized by ligand exchange. • Thin film transistors (TFTs) of colloidal NCs were fabricated by spin-coating method. • Water-soluble In{sub 2}O{sub 3} NC TFTs showed higher mobilities due to shorter ligand length. • Surface defects of NCs were notably reduced by surface etching during ligand exchange.

Discovering rules for protein-ligand specificity using support vector inductive logic programming.

Science.gov (United States)

Kelley, Lawrence A; Shrimpton, Paul J; Muggleton, Stephen H; Sternberg, Michael J E

2009-09-01

Structural genomics initiatives are rapidly generating vast numbers of protein structures. Comparative modelling is also capable of producing accurate structural models for many protein sequences. However, for many of the known structures, functions are not yet determined, and in many modelling tasks, an accurate structural model does not necessarily tell us about function. Thus, there is a pressing need for high-throughput methods for determining function from structure. The spatial arrangement of key amino acids in a folded protein, on the surface or buried in clefts, is often the determinants of its biological function. A central aim of molecular biology is to understand the relationship between such substructures or surfaces and biological function, leading both to function prediction and to function design. We present a new general method for discovering the features of binding pockets that confer specificity for particular ligands. Using a recently developed machine-learning technique which couples the rule-discovery approach of inductive logic programming with the statistical learning power of support vector machines, we are able to discriminate, with high precision (90%) and recall (86%) between pockets that bind FAD and those that bind NAD on a large benchmark set given only the geometry and composition of the backbone of the binding pocket without the use of docking. In addition, we learn rules governing this specificity which can feed into protein functional design protocols. An analysis of the rules found suggests that key features of the binding pocket may be tied to conformational freedom in the ligand. The representation is sufficiently general to be applicable to any discriminatory binding problem. All programs and data sets are freely available to non-commercial users at http://www.sbg.bio.ic.ac.uk/svilp_ligand/.

The role of ligands in the optical and electronic spectra of CdSe nanoclusters

Energy Technology Data Exchange (ETDEWEB)

Kilina, Svletana [Los Alamos National Laboratory; Sergei, Ivanov A [Los Alamos National Laboratory; Victor, Klimov I [Los Alamos National Laboratory; Sergei, Tretiak [Los Alamos National Laboratory

2008-01-01

We investigate the impact of ligands on morphology, electronic structure, and optical response of the Cd33Se33 cluster, which already overlapps in size with the smallest synthesized CdSe quantum dots (QDs). Our Density Functional Theory (DFT) calculations demonstrate significant surface reorganization both for the bare cluster and for the cluster capped by amine and phosphine oxide ligand models. We observe strong surface-ligand interactions leading to substantial charge redistribution and polarization effects on the surface. This effect results in the appearance of hybridized states, where the electronic density is spread over the cluster and the ligands. Neither the ligand's nor hybridized molecular orbitals appear as trap states inside or near the band gap of the QD. Instead, being optically dark, dense hybridized states from the edges of the valence and the conduction bands could open new relaxation channels for high energy photoexcitations. Comparing quantum dots passivated by different ligands, we found that hybridized states are denser in at the edge of the conduction band of the cluster ligated with phosphine oxide molecules than that with primary amines. Such a different manifestation of ligand binding may potentially lead to the faster electron relaxation in dots passivated by phosphine oxide than by amine ligands, which is in agreement with experimental data.

Surface potential-governed cellular osteogenic differentiation on ferroelectric polyvinylidene fluoride trifluoroethylene films.

Science.gov (United States)

Tang, Bolin; Zhang, Bo; Zhuang, Junjun; Wang, Qi; Dong, Lingqing; Cheng, Kui; Weng, Wenjian

2018-05-02

Surface potential of biomaterials can dramatically influence cellular osteogenic differentiation. In this work, a wide range of surface potential on ferroelectric polyvinylidene fluoride trifluoroethylene (P(VDF-TrFE)) films was designed to get insight into the interfacial interaction of cell-charged surface. The P(VDF-TrFE) films poled by contact electric poling at various electric fields obtained well stabilized surface potential, with wide range from -3 to 915 mV. The osteogenic differentiation level of cells cultured on the films was strongly dependent on surface potential and reached the optimum at 391 mV in this system. Binding specificity assay indicated that surface potential could effectively govern the binding state of the adsorbed fibronectin (FN) with integrin. Molecular dynamic (MD) simulation further revealed that surface potential brought a significant difference in the relative distance between RGD and synergy PHSRN sites of adsorbed FN, resulting in a distinct integrin-FN binding state. These results suggest that the full binding of integrin α5β1 with both RGD and PHSRN sites of FN possesses a strong ability to activate osteogenic signaling pathway. This work sheds light on the underlying mechanism of osteogenic differentiation behavior on charged material surfaces, and also provides a guidance for designing a reasonable charged surface to enhance osteogenic differentiation. The ferroelectric P(VDF-TrFE) films with steady and a wide range of surface potential were designed to understand underlying mechanism of cell-charged surface interaction. The results showed that the charged surface well favored upregulation of osteogenic differentiation of MC3T3-E1 cells, and more importantly, a highest level occurred on the film with a moderate surface potential. Experiments and molecular dynamics simulation demonstrated that the surface potential could govern fibronectin conformation and then the integrin-fibronectin binding. We propose that a full binding

Nucleolin inhibits Fas ligand binding and suppresses Fas-mediated apoptosis in vivo via a surface nucleolin-Fas complex.

Science.gov (United States)

Wise, Jillian F; Berkova, Zuzana; Mathur, Rohit; Zhu, Haifeng; Braun, Frank K; Tao, Rong-Hua; Sabichi, Anita L; Ao, Xue; Maeng, Hoyoung; Samaniego, Felipe

2013-06-06

Resistance to Fas-mediated apoptosis is associated with poor cancer outcomes and chemoresistance. To elucidate potential mechanisms of defective Fas signaling, we screened primary lymphoma cell extracts for Fas-associated proteins that would have the potential to regulate Fas signaling. An activation-resistant Fas complex selectively included nucleolin. We confirmed the presence of nucleolin-Fas complexes in B-cell lymphoma cells and primary tissues, and the absence of such complexes in B-lymphocytes from healthy donors. RNA-binding domain 4 and the glycine/arginine-rich domain of nucleolin were essential for its association with Fas. Nucleolin colocalized with Fas on the surface of B-cell lymphoma cells. Nucleolin knockdown sensitized BJAB cells to Fas ligand (FasL)-induced and Fas agonistic antibody-induced apoptosis through enhanced binding, suggesting that nucleolin blocks the FasL-Fas interaction. Mice transfected with nucleolin were protected from the lethal effects of agonistic anti-mouse Fas antibody (Jo2) and had lower rates of hepatocyte apoptosis, compared with vector and a non-Fas-binding mutant of nucleolin. Our results show that cell surface nucleolin binds Fas, inhibits ligand binding, and thus prevents induction of Fas-mediated apoptosis in B-cell lymphomas and may serve as a new therapeutic target.

Ligand Exchange Kinetics of Environmentally Relevant Metals

Energy Technology Data Exchange (ETDEWEB)

Panasci, Adele Frances [Univ. of California, Davis, CA (United States)

2014-07-15

The interactions of ground water with minerals and contaminants are of broad interest for geochemists but are not well understood. Experiments on the molecular scale can determine reaction parameters (i.e. rates of ligand exchange, activation entropy, activation entropy, and activation volume) that can be used in computations to gain insight into reactions that occur in natural groundwaters. Experiments to determine the rate of isotopic ligand exchange for three environmentally relevant metals, rhodium (Rh), iron (Fe), and neptunium (Np), are described. Many environmental transformations of metals (e.g. reduction) in soil occur at trivalent centers, Fe(III) in particular. Contaminant ions absorb to mineral surfaces via ligand exchange, and the reversal of this reaction can be dangerous, releasing contaminants into the environment. Ferric iron is difficult to study spectroscopically because most of its complexes are paramagnetic and are generally reactive toward ligand exchange; therefore, Rh(III), which is diamagnetic and less reactive, was used to study substitution reactions that are analogous to those that occur on mineral oxide surfaces. Studies on both Np(V) and Np(VI) are important in their own right, as ²³⁷Np is a radioactive transuranic element with a half-life of 2 million years.

Exploring the role of water in molecular recognition: predicting protein ligandability using a combinatorial search of surface hydration sites

Science.gov (United States)

Vukovic, Sinisa; Brennan, Paul E.; Huggins, David J.

2016-09-01

The interaction between any two biological molecules must compete with their interaction with water molecules. This makes water the most important molecule in medicine, as it controls the interactions of every therapeutic with its target. A small molecule binding to a protein is able to recognize a unique binding site on a protein by displacing bound water molecules from specific hydration sites. Quantifying the interactions of these water molecules allows us to estimate the potential of the protein to bind a small molecule. This is referred to as ligandability. In the study, we describe a method to predict ligandability by performing a search of all possible combinations of hydration sites on protein surfaces. We predict ligandability as the summed binding free energy for each of the constituent hydration sites, computed using inhomogeneous fluid solvation theory. We compared the predicted ligandability with the maximum observed binding affinity for 20 proteins in the human bromodomain family. Based on this comparison, it was determined that effective inhibitors have been developed for the majority of bromodomains, in the range from 10 to 100 nM. However, we predict that more potent inhibitors can be developed for the bromodomains BPTF and BRD7 with relative ease, but that further efforts to develop inhibitors for ATAD2 will be extremely challenging. We have also made predictions for the 14 bromodomains with no reported small molecule K d values by isothermal titration calorimetry. The calculations predict that PBRM1(1) will be a challenging target, while others such as TAF1L(2), PBRM1(4) and TAF1(2), should be highly ligandable. As an outcome of this work, we assembled a database of experimental maximal K d that can serve as a community resource assisting medicinal chemistry efforts focused on BRDs. Effective prediction of ligandability would be a very useful tool in the drug discovery process.

Exploring the role of water in molecular recognition: predicting protein ligandability using a combinatorial search of surface hydration sites.

Science.gov (United States)

Vukovic, Sinisa; Brennan, Paul E; Huggins, David J

2016-09-01

The interaction between any two biological molecules must compete with their interaction with water molecules. This makes water the most important molecule in medicine, as it controls the interactions of every therapeutic with its target. A small molecule binding to a protein is able to recognize a unique binding site on a protein by displacing bound water molecules from specific hydration sites. Quantifying the interactions of these water molecules allows us to estimate the potential of the protein to bind a small molecule. This is referred to as ligandability. In the study, we describe a method to predict ligandability by performing a search of all possible combinations of hydration sites on protein surfaces. We predict ligandability as the summed binding free energy for each of the constituent hydration sites, computed using inhomogeneous fluid solvation theory. We compared the predicted ligandability with the maximum observed binding affinity for 20 proteins in the human bromodomain family. Based on this comparison, it was determined that effective inhibitors have been developed for the majority of bromodomains, in the range from 10 to 100 nM. However, we predict that more potent inhibitors can be developed for the bromodomains BPTF and BRD7 with relative ease, but that further efforts to develop inhibitors for ATAD2 will be extremely challenging. We have also made predictions for the 14 bromodomains with no reported small molecule K d values by isothermal titration calorimetry. The calculations predict that PBRM1(1) will be a challenging target, while others such as TAF1L(2), PBRM1(4) and TAF1(2), should be highly ligandable. As an outcome of this work, we assembled a database of experimental maximal K d that can serve as a community resource assisting medicinal chemistry efforts focused on BRDs. Effective prediction of ligandability would be a very useful tool in the drug discovery process.

Autocrine signal transmission with extracellular ligand degradation

International Nuclear Information System (INIS)

Muratov, C B; Posta, F; Shvartsman, S Y

2009-01-01

Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand–receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers

Copper complexing ligands and organic matter characterization in the northern Adriatic Sea

Science.gov (United States)

Plavšić, Marta; Gašparović, Blaženka; Strmečki, Slađana; Vojvodić, Vjeročka; Tepić, Nataša

2009-11-01

The study on dissolved organic ligands capable to complex copper ions (L T), surface-active substances (SAS) and dissolved organic carbon (DOC) in the Northern Adriatic Sea station (ST 101) under the influence of Po River was conducted in period from 2006-2008. The acidity of surface-active organic material (Ac r) was followed as well. The results are compared to temperature and salinity distributions. On that way, the contribution of the different pools of ligands capable to complex Cu ions could be determined as well as the influence of aging and transformation of the organic matter. The L T values in the investigated period were in the range of 40-300 nmol l -1. The range of DOC values for surface and bottom samples were 0.84-1.87 mg l -1 and 0.80-1.30 mg l -1, respectively. Total SAS concentrations in the bottom layer were 0.045-0.098 mg l -1 in equiv. of Triton-X-100 while those in the surface layer were 0.050-0.143 mg l -1 in equiv. of Triton-X-100. The majority of organic ligands responsible for Cu binding in surface water originate from new phytoplankton production promoted by river borne nutrients. Older, transformed organic matter, possessing higher relative acidity, is the main contributor to the pool of organic ligands that bind copper in the bottom samples. It was estimated that ˜9% of DOC in surface samples and ˜12% of DOC in the bottom samples are present as ligands capable to complex copper ions.

Characterization, cell-surface expression and ligand-binding properties of different truncated N-terminal extracellular domains of the ionotropic glutamate receptor subunit GluR1.

Science.gov (United States)

McIlhinney, R A; Molnár, E

1996-04-01

To identify the location of the first transmembrane segment of the GluR1 glutamate receptor subunit artificial stop codons have been introduced into the N-terminal domain at amino acid positions 442, 510, and 563, namely just before and spanning the proposed first two transmembrane regions. The resultant truncated N-terminal fragments of GluR1, termed NT1, NT2, and NT3 respectively were expressed in Cos-7 cells and their cellular distribution and cell-surface expression analysed using an N-terminal antibody to GluR1. All of the fragments were fully glycosylated and were found to be associated with cell membranes but none was secreted. Differential extraction of the cell membranes indicated that both NT1 and NT2 behave as peripheral membrane proteins. In contrast NT3, like the full subunit, has integral membrane protein properties. Furthermore only NT3 is expressed at the cell surface as determined by immunofluorescence and cell-surface biotinylation. Protease protection assays indicated that only NT3 had a cytoplasmic tail. Binding studies using the selective ligand [(3)H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate ([(3)H]AMPA) demonstrated that NT3 does not bind ligand. Together these results indicate that the first transmembrane domain of the GluR1 subunit lies between residues 509 and 562, that the N-terminal domain alone cannot form a functional ligand-binding site and that this domain can be targeted to the cell surface provided that it has a transmembrane-spanning region.

Architecture effects on multivalent interactions by polypeptide-based multivalent ligands

Science.gov (United States)

Liu, Shuang

Multivalent interactions are characterized by the simultaneous binding between multiple ligands and multiple binding sites, either in solutions or at interfaces. In biological systems, most multivalent interactions occur between protein receptors and carbohydrate ligands through hydrogen-bonding and hydrophobic interactions. Compared with weak affinity binding between one ligand and one binding site, i.e. monovalent interaction, multivalent interactioins provide greater avidity and specificity, and therefore play unique roles in a broad range of biological activities. Moreover, the studies of multivalent interactions are also essential for producing effective inhibitors and effectors of biological processes that could have important therapeutic applications. Synthetic multivalent ligands have been designed to mimic the biological functions of natural multivalent interactions, and various types of scaffolds have been used to display multiple ligands, including small molecules, linear polymers, dendrimers, nanoparticle surfaces, monolayer surfaces and liposomes. Studies have shown that multivalent interactions can be highly affected by various architectural parameters of these multivalent ligands, including ligand identities, valencies, spacing, ligand densities, nature of linker arms, scaffold length and scaffold conformation. Most of these multivalent ligands are chemically synthesized and have limitations of controlling over sequence and conformation, which is a barrier for mimicking ordered and controlled natural biological systems. Therefore, multivalent ligands with precisely controlled architecture are required for improved structure-function relationship studies. Protein engineering methods with subsequent chemical coupling of ligands provide significant advantages of controlling over backbone conformation and functional group placement, and therefore have been used to synthesize recombinant protein-based materials with desired properties similar to natural

Statistical Estimation of the Protein-Ligand Binding Free Energy Based On Direct Protein-Ligand Interaction Obtained by Molecular Dynamics Simulation

Directory of Open Access Journals (Sweden)

Haruki Nakamura

2012-09-01

Full Text Available We have developed a method for estimating protein-ligand binding free energy (DG based on the direct protein-ligand interaction obtained by a molecular dynamics simulation. Using this method, we estimated the DG value statistically by the average values of the van der Waals and electrostatic interactions between each amino acid of the target protein and the ligand molecule. In addition, we introduced fluctuations in the accessible surface area (ASA and dihedral angles of the protein-ligand complex system as the entropy terms of the DG estimation. The present method included the fluctuation term of structural change of the protein and the effective dielectric constant. We applied this method to 34 protein-ligand complex structures. As a result, the correlation coefficient between the experimental and calculated DG values was 0.81, and the average error of DG was 1.2 kcal/mol with the use of the fixed parameters. These results were obtained from a 2 nsec molecular dynamics simulation.

Selective Electrocatalytic Activity of Ligand Stabilized Copper Oxide Nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Kauffman, Douglas R; Ohodnicki, Paul R; Kail, Brian W; Matranga, Christopher

2011-01-01

Ligand stabilization can influence the surface chemistry of Cu oxide nanoparticles (NPs) and provide unique product distributions for electrocatalytic methanol (MeOH) oxidation and CO{sub 2} reduction reactions. Oleic acid (OA) stabilized Cu{sub 2}O and CuO NPs promote the MeOH oxidation reaction with 88% and 99.97% selective HCOH formation, respectively. Alternatively, CO{sub 2} is the only reaction product detected for bulk Cu oxides and Cu oxide NPs with no ligands or weakly interacting ligands. We also demonstrate that OA stabilized Cu oxide NPs can reduce CO{sub 2} into CO with a {approx}1.7-fold increase in CO/H{sub 2} production ratios compared to bulk Cu oxides. The OA stabilized Cu oxide NPs also show 7.6 and 9.1-fold increases in CO/H{sub 2} production ratios compared to weakly stabilized and non-stabilized Cu oxide NPs, respectively. Our data illustrates that the presence and type of surface ligand can substantially influence the catalytic product selectivity of Cu oxide NPs.

PatchSurfers: Two methods for local molecular property-based binding ligand prediction.

Science.gov (United States)

Shin, Woong-Hee; Bures, Mark Gregory; Kihara, Daisuke

2016-01-15

Protein function prediction is an active area of research in computational biology. Function prediction can help biologists make hypotheses for characterization of genes and help interpret biological assays, and thus is a productive area for collaboration between experimental and computational biologists. Among various function prediction methods, predicting binding ligand molecules for a target protein is an important class because ligand binding events for a protein are usually closely intertwined with the proteins' biological function, and also because predicted binding ligands can often be directly tested by biochemical assays. Binding ligand prediction methods can be classified into two types: those which are based on protein-protein (or pocket-pocket) comparison, and those that compare a target pocket directly to ligands. Recently, our group proposed two computational binding ligand prediction methods, Patch-Surfer, which is a pocket-pocket comparison method, and PL-PatchSurfer, which compares a pocket to ligand molecules. The two programs apply surface patch-based descriptions to calculate similarity or complementarity between molecules. A surface patch is characterized by physicochemical properties such as shape, hydrophobicity, and electrostatic potentials. These properties on the surface are represented using three-dimensional Zernike descriptors (3DZD), which are based on a series expansion of a 3 dimensional function. Utilizing 3DZD for describing the physicochemical properties has two main advantages: (1) rotational invariance and (2) fast comparison. Here, we introduce Patch-Surfer and PL-PatchSurfer with an emphasis on PL-PatchSurfer, which is more recently developed. Illustrative examples of PL-PatchSurfer performance on binding ligand prediction as well as virtual drug screening are also provided. Copyright © 2015 Elsevier Inc. All rights reserved.

Surfactant Ligand Removal and Rational Fabrication of Inorganically Connected Quantum Dots

KAUST Repository

Zhang, Haitao; Hu, Bo; Sun, Liangfeng; Hovden, Robert; Wise, Frank W.; Muller, David A.; Robinson, Richard D.

2011-01-01

in that no new surfactant ligands are introduced and the post-treated NC surfaces are nearly bare. The detailed mechanism study shows that the high reactivity between (NH 4) 2S and metal-surfactant ligand complexes enables the complete removal of surfactant

NKG2D and its ligands in cancer.

Science.gov (United States)

Dhar, Payal; Wu, Jennifer D

2018-04-01

NKG2D is an activating immune receptor expressed by NK and effector T cells. Induced expression of NKG2D ligand on tumor cell surface during oncogenic insults renders cancer cells susceptible to immune destruction. In advanced human cancers, tumor cells shed NKG2D ligand to produce an immune soluble form as a means of immune evasion. Soluble NKG2D ligands have been associated with poor clinical prognosis in cancer patients. Harnessing NKG2D pathway is considered a viable avenue in cancer immunotherapy over recent years. In this review, we will discuss the progress and perspectives. Copyright © 2018. Published by Elsevier Ltd.

Dependence of cancer cell adhesion kinetics on integrin ligand surface density measured by a high-throughput label-free resonant waveguide grating biosensor.

Science.gov (United States)

Orgovan, Norbert; Peter, Beatrix; Bősze, Szilvia; Ramsden, Jeremy J; Szabó, Bálint; Horvath, Robert

2014-02-07

A novel high-throughput label-free resonant waveguide grating (RWG) imager biosensor, the Epic® BenchTop (BT), was utilized to determine the dependence of cell spreading kinetics on the average surface density (v(RGD)) of integrin ligand RGD-motifs. v(RGD) was tuned over four orders of magnitude by co-adsorbing the biologically inactive PLL-g-PEG and the RGD-functionalized PLL-g-PEG-RGD synthetic copolymers from their mixed solutions onto the sensor surface. Using highly adherent human cervical tumor (HeLa) cells as a model system, cell adhesion kinetic data of unprecedented quality were obtained. Spreading kinetics were fitted with the logistic equation to obtain the spreading rate constant (r) and the maximum biosensor response (Δλmax), which is assumed to be directly proportional to the maximum spread contact area (Amax). r was found to be independent of the surface density of integrin ligands. In contrast, Δλmax increased with increasing RGD surface density until saturation at high densities. Interpreting the latter behavior with a simple kinetic mass action model, a 2D dissociation constant of 1753 ± 243 μm(-2) (corresponding to a 3D dissociation constant of ~30 μM) was obtained for the binding between RGD-specific integrins embedded in the cell membrane and PLL-g-PEG-RGD. All of these results were obtained completely noninvasively without using any labels.

Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity*

Science.gov (United States)

Marty, Caroline; Chaligné, Ronan; Lacout, Catherine; Constantinescu, Stefan N.; Vainchenker, William; Villeval, Jean-Luc

2009-01-01

The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia. MPL belongs to a subset of the cytokine receptor superfamily that requires the JAK2 kinase for signaling. We examined whether the ligand-independent MPLW515L mutant could signal intracellularly. Addition of the endoplasmic reticulum (ER) retention KDEL sequence to the receptor C terminus efficiently locked MPLW515L within its natural ER/Golgi maturation pathway. In contrast to cells expressing the parental MPLW515L, MPLW515L-KDEL-expressing FDC-P1 cells were unable to grow autonomously and to produce tumors in nude mice. When observed, tumor nodules resulted from in vivo selection of cells leaking the receptor at their surface. JAK2 co-immunoprecipitated with MPLW515L-KDEL but was not phosphorylated. We generated disulfide-bonded MPLW515L homodimers by the S402C substitution, both in the normal and KDEL context. Unlike MPLW515L-KDEL, MPLW515L-S402C-KDEL signaled constitutively and exhibited cell surface localization. These data establish that MPLW515L with appended JAK2 matures through the ER/Golgi system in an inactive conformation and suggest that the MPLW515L/JAK2 complex requires membrane localization for JAK2 phosphorylation, resulting in autonomous receptor signaling. PMID:19261614

Covalent attachment of pyridine-type molecules to glassy carbon surfaces by electrochemical reduction of in situ generated diazonium salts. Formation of ruthenium complexes on ligand-modified surfaces

International Nuclear Information System (INIS)

Yesildag, Ali; Ekinci, Duygu

2010-01-01

In this study, pyridine, quinoline and phenanthroline molecules were covalently bonded to glassy carbon (GC) electrode surfaces for the first time using the diazonium modification method. Then, the complexation ability of the modified films with ruthenium metal cations was investigated. The derivatization of GC surfaces with heteroaromatic molecules was achieved by electrochemical reduction of the corresponding in situ generated diazonium salts. X-ray photoelectron spectroscopy (XPS) was used to confirm the attachment of heteroaromatic molecules to the GC surfaces and to determine the surface concentration of the films. The barrier properties of the modified GC electrodes were studied in the presence of redox probes such as Fe(CN) 6 3- and Ru(NH 3 ) 6 3+ by cyclic voltammetry. Additionally, the presence of the resulting organometallic films on the surfaces was verified by XPS after the chemical transformation of the characterized ligand films to the ruthenium complex films. The electrochemical behavior of these films in acetonitrile solution was investigated using voltammetric methods, and the surface coverage of the organometallic films was determined from the reversible metal-based Ru(II)/Ru(III) oxidation waves.

Doping Control Via Molecularly Engineered Surface Ligand Coordination

KAUST Repository

Yuan, Mingjian; Zhitomirsky, David; Adinolfi, Valerio; Voznyy, Oleksandr; Kemp, Kyle W.; Ning, Zhijun; Lan, Xinzheng; Xu, Jixian; Kim, Jin Young; Dong, Haopeng; Sargent, Edward H.

2013-01-01

A means to control the net doping of a CQD solid is identified via the design of the bidentate ligand crosslinking the material. The strategy does not rely on implementing different atmospheres at different steps in device processing, but instead is a robust strategy implemented in a single processing ambient. We achieve an order of magnitude difference in doping that allows us to build a graded photovoltaic device and maintain high current and voltage at maximum power-point conditions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Doping Control Via Molecularly Engineered Surface Ligand Coordination

KAUST Repository

Yuan, Mingjian

2013-08-05

A means to control the net doping of a CQD solid is identified via the design of the bidentate ligand crosslinking the material. The strategy does not rely on implementing different atmospheres at different steps in device processing, but instead is a robust strategy implemented in a single processing ambient. We achieve an order of magnitude difference in doping that allows us to build a graded photovoltaic device and maintain high current and voltage at maximum power-point conditions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CO2 activation through silylimido and silylamido zirconium hydrides supported on N-donor chelating SBA15 surface ligand

KAUST Repository

Pasha, Fahran Ahmad

2016-01-04

Density functional theory calculations and 2D 1H-13C HETCOR solid state NMR spectroscopy prove that CO2 can probe, by its own reactivity, different types of N-donor surface ligands on SBA15-supported ZrIV hydrides: [(≡Si-O-)(≡Si-N=)[Zr]H] and [(≡Si-NH-)(≡Si-X-)[Zr]H2] (X = O or NH). Moreover, [(≡Si-O-)(≡Si-N=)[Zr]H] activates CO2 more efficiently than the other complexes and leads to a carbimato Zr formate.

Multiscale simulations of ligand adsorption and exchange on gold nanoparticles.

Science.gov (United States)

Gao, Hui-Min; Liu, Hong; Qian, Hu-Jun; Jiao, Gui-Sheng; Lu, Zhong-Yuan

2018-01-17

We have developed a multiscale model that combines first-principles methods with atomistic and mesoscopic simulations to explore the molecular structures and packing density of the ligands present on the gold nanoparticle (AuNP) surface, as well as the adsorption/exchange reaction kinetics of cetyltrimethylammonium bromide (CTAB)/PEG-SH ligands on different facets of gold, namely, Au(111), Au(100), and Au(110). Our model predicts that on clean gold surfaces, CTAB adsorption is diffusion limited. Specifically, CTAB has the preferentially higher adsorption rate and coverage density on Au(100) and Au(110) surfaces, forming a more compact layer with respect to that on the Au(111) surface, which could result in greater growth of gold nanoparticles along the (111) direction. As opposed to CTAB adsorption, the exchange reaction between PEG-SH with CTAB shows no selectivity to different crystal faces, and the reaction process follows Langmuir diffusion kinetics. Kinetic analysis reveals that, in water, the exchange reaction is zeroth order with respect to the concentration of an incoming PEG-SH, indicative of a dissociative exchange mechanism. The observed rate constant decreases exponentially with the PEG-SH chain length, consistent with a diffusion process for the free PEG-SH in water. In particular, we show that the exchange efficiency increases as the chain rigidness and size of the incoming ligand and/or steric bulk of the initial protecting ligand shell are decreased. Our objectives are to provide a model to assess the kinetics and thermodynamics of the adsorption/exchange reaction process, and we expect that these findings will have important implications for routine surface characterization of AuNPs.

Cavity Versus Ligand Shape Descriptors: Application to Urokinase Binding Pockets.

Science.gov (United States)

Cerisier, Natacha; Regad, Leslie; Triki, Dhoha; Camproux, Anne-Claude; Petitjean, Michel

2017-11-01

We analyzed 78 binding pockets of the human urokinase plasminogen activator (uPA) catalytic domain extracted from a data set of crystallized uPA-ligand complexes. These binding pockets were computed with an original geometric method that does NOT involve any arbitrary parameter, such as cutoff distances, angles, and so on. We measured the deviation from convexity of each pocket shape with the pocket convexity index (PCI). We defined a new pocket descriptor called distributional sphericity coefficient (DISC), which indicates to which extent the protein atoms of a given pocket lie on the surface of a sphere. The DISC values were computed with the freeware PCI. The pocket descriptors and their high correspondences with ligand descriptors are crucial for polypharmacology prediction. We found that the protein heavy atoms lining the urokinases binding pockets are either located on the surface of their convex hull or lie close to this surface. We also found that the radii of the urokinases binding pockets and the radii of their ligands are highly correlated (r = 0.9).

Ligand-dependent exciton dynamics and photovoltaic properties of PbS quantum dot heterojunction solar cells.

Science.gov (United States)

Chang, Jin; Ogomi, Yuhei; Ding, Chao; Zhang, Yao Hong; Toyoda, Taro; Hayase, Shuzi; Katayama, Kenji; Shen, Qing

2017-03-01

The surface chemistry of colloidal quantum dots (QDs) plays an important role in determining the photoelectric properties of QD films and the corresponding quantum dot heterojunction solar cells (QDHSCs). To investigate the effects of the ligand structure on the photovoltaic performance and exciton dynamics of QDHSCs, PbS QDHSCs were fabricated by the solid state ligand exchange method with mercaptoalkanoic acid as the cross-linking ligand. Temperature-dependent photoluminescence and ultrafast transient absorption spectra show that the electronic coupling and charge transfer rate within QD ensembles were monotonically enhanced as the ligand length decreased. However, in practical QDHSCs, the second shortest ligand 3-mercaptopropionic acid (MPA) showed higher power conversion efficiency than the shortest ligand thioglycolic acid (TGA). This could be attributed to the difference in their surface trap states, supported by thermally stimulated current measurements. Moreover, compared with the non-conjugated ligand MPA, the conjugated ligand 4-mercaptobenzoic acid (MBA) introduces less trap states and has a similar charge transfer rate in QD ensembles, but has poor photovoltaic properties. This unexpected result could be contributed by the QD-ligand orbital mixing, leading to the charge transfer from QDs to ligands instead of charge transfer between adjacent QDs. This work highlights the significant effects of ligand structures on the photovoltaic properties and exciton dynamics of QDHSCs, which would shed light on the further development of QD-based photoelectric devices.

Surface anisotropy of iron oxide nanoparticles and slabs from first principles: Influence of coatings and ligands as a test of the Heisenberg model

Energy Technology Data Exchange (ETDEWEB)

Brymora, Katarzyna; Calvayrac, Florent, E-mail: Florent.Calvayrac@univ-lemans.fr

2017-07-15

Highlights: • A new method is given to extract surface anisotropies from ab initio calculations. • Heisenberg model for magnetic clusters and surfaces is validated in simple cases. • Ligands, metallic clusters, or coatings degrade the validity of the Heisenberg model. • Values for surface anisotropies, volume anisotropies, exchange constants are computed. • Results are in agreement with experimental data, previous theoretical findings. - Abstract: We performed ab initio computations of the magnetic properties of simple iron oxide clusters and slabs. We considered an iron oxide cluster functionalized by a molecule or glued to a gold cluster of the same size. We also considered a magnetite slab coated by cobalt oxide or a mixture of iron oxide and cobalt oxide. The changes in magnetic behavior were explored using constrained magnetic calculations. A possible value for the surface anisotropy was estimated from the fit of a classical Heisenberg model on ab initio results. The value was found to be compatible with estimations obtained by other means, or inferred from experimental results. The addition of a ligand, coating, or of a metallic nanoparticle to the systems degraded the quality of the description by the Heisenberg Hamiltonian. Proposing a change in the anisotropies allowing for the proportion of each transition atom we could get a much better description of the magnetism of series of hybrid cobalt and iron oxide systems.

Ligand mobility modulates immunological synapse formation and T cell activation.

Directory of Open Access Journals (Sweden)

Chih-Jung Hsu

Full Text Available T cell receptor (TCR engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70 and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76. This molecular rearrangement results in formation of the immunological synapse (IS, a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca(2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses.

Exploring the composition of protein-ligand binding sites on a large scale.

Directory of Open Access Journals (Sweden)

Nickolay A Khazanov

Full Text Available The residue composition of a ligand binding site determines the interactions available for diffusion-mediated ligand binding, and understanding general composition of these sites is of great importance if we are to gain insight into the functional diversity of the proteome. Many structure-based drug design methods utilize such heuristic information for improving prediction or characterization of ligand-binding sites in proteins of unknown function. The Binding MOAD database if one of the largest curated sets of protein-ligand complexes, and provides a source of diverse, high-quality data for establishing general trends of residue composition from currently available protein structures. We present an analysis of 3,295 non-redundant proteins with 9,114 non-redundant binding sites to identify residues over-represented in binding regions versus the rest of the protein surface. The Binding MOAD database delineates biologically-relevant "valid" ligands from "invalid" small-molecule ligands bound to the protein. Invalids are present in the crystallization medium and serve no known biological function. Contacts are found to differ between these classes of ligands, indicating that residue composition of biologically relevant binding sites is distinct not only from the rest of the protein surface, but also from surface regions capable of opportunistic binding of non-functional small molecules. To confirm these trends, we perform a rigorous analysis of the variation of residue propensity with respect to the size of the dataset and the content bias inherent in structure sets obtained from a large protein structure database. The optimal size of the dataset for establishing general trends of residue propensities, as well as strategies for assessing the significance of such trends, are suggested for future studies of binding-site composition.

Gut microbiota regulates NKG2D ligand expression on intestinal epithelial cells

DEFF Research Database (Denmark)

Hansen, Camilla Hartmann Friis; Holm, Thomas L.; Krych, Lukasz

2013-01-01

Intestinal epithelial cells (IECs) are one of a few cell types in the body with constitutive surface expression of natural killer group 2 member D (NKG2D) ligands, although the magnitude of ligand expression by IECs varies. Here, we investigated whether the gut microbiota regulates the NKG2D ligand...... expression is kept in check by an intestinal regulatory immune milieu induced by members of the gut microbiota, for example A. muciniphila....

Organic ligand-induced dissolution kinetics of antimony trioxide

Institute of Scientific and Technical Information of China (English)

Xingyun Hu; Mengchang He

2017-01-01

The influence of low-molecular-weight dissolved organic matter (LMWDOM) on the dissolution rate of Sb2O3 was investigated.Some representative LMWDOMs with carboxyl,hydroxyl,hydrosulfuryl and amidogen groups occurring naturally in the solution were chosen,namely oxalic acid,citric acid,tartaric acid,EDTA,salicylic acid,phthalandione,glycine,thiolactic acid,xylitol,glucose and catechol.These LMWDOMs were dissolved in inert buffers at pH =3.7,6.6 and 8.6 and added to powdered Sb2O3 in a stirred,thermostatted reactor (25℃).The addition of EDTA,tartaric acid,thiolactic acid,citric acid and oxalic acid solutions at pH 3.7 and catechol at pH 8.6 increased the rate of release of antimony.In the 10 mmol/L thiolactic acid solution,up to 97％ by mass of the antimony was released after 120 min reaction.There was no effect on the dissolution of Sb2O3 for the other ligands.A weak correlation between dissolution rate with the dissociation constant of ligands and the stability of the dissolved complex was also found.All the results showed that the extent of the promoting effect of ligands on the dissolution of Sb2O3 was not determined by the stability of the dissolved complex,but by the dissociation constant of ligands and detachment rate of surface chelates from the mineral surface.This study can not only help in further understanding the effect of individual low-molecular-weight organic ligands,but also provides a reference to deduce the effect of natural organic matters with oxygen-bearing functional groups on the dissolution of antimony oxide minerals.

Phenanthroline-2,9-bistriazoles as selective G-quadruplex ligands

DEFF Research Database (Denmark)

Nielsen, Mads Corvinius; Larsen, Anders Foller; Abdikadir, Faisal Hussein

2014-01-01

G-quadruplex (G4) ligands are currently receiving considerable attention as potential anticancer therapeutics. A series of phenanthroline-2,9-bistriazoles carrying tethered positive end groups has been synthesized and evaluated as G4 stabilizers. The compounds were efficiently assembled by copper......(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in CH2Cl2 and water in the presence of a complexing agent. Characterization of the target compounds on telomeric and c-KIT G4 sequences led to the identification of guanidinium-substituted compounds as potent G4 DNA ligands with high selectivity over duplex DNA....... The diisopropylguanidium ligands exhibited high selectivity for the proto-oncogenic sequence c-KIT over the human telomeric sequence in the surface plasmon resonance (SPR) assay, whereas the compounds appeared potent on both G4 structures in the FRET melting temperature assay. The phenanthroline-2,9-bistriazole ligands...

Assessing potential peptide targeting ligands by quantification of cellular adhesion of model nanoparticles under flow conditions.

Science.gov (United States)

Broda, Ellen; Mickler, Frauke Martina; Lächelt, Ulrich; Morys, Stephan; Wagner, Ernst; Bräuchle, Christoph

2015-09-10

Sophisticated drug delivery systems are coated with targeting ligands to improve the specific adhesion to surface receptors on diseased cells. In our study, we developed a method with which we assessed the potential of peptide ligands to specifically bind to receptor overexpressing target cells. Therefore, a microfluidic setup was used where the cellular adhesion of nanoparticles with ligand and of control nanoparticles was observed in parallel under the same experimental conditions. The effect of the ligand on cellular binding was quantified by counting the number of adhered nanoparticles with ligand and differently labeled control nanoparticles on single cells after incubation under flow conditions. To provide easy-to-synthesize, stable and reproducible nanoparticles which mimic the surface characteristics of drug delivery systems and meet the requirements for quantitative analysis, latex beads based on amine-modified polystyrene were used as model nanoparticles. Two short peptides were tested to serve as targeting ligand on the beads by increasing the specific binding to HuH7 cells. The c-Met binding peptide cMBP2 was used for hepatocyte growth factor receptor (c-Met) targeting and the peptide B6 for transferrin receptor (TfR) targeting. The impact of the targeting peptide on binding was investigated by comparing the beads with ligand to different internal control beads: 1) without ligand and tailored surface charge (electrostatic control) and 2) with scrambled peptide and similar surface charge, but a different amino acid sequence (specificity control). Our results demonstrate that the method is very useful to select suitable targeting ligands for specific nanoparticle binding to receptor overexpressing tumor cells. We show that the cMBP2 ligand specifically enhances nanoparticle adhesion to target cells, whereas the B6 peptide mediates binding to tumor cells mainly by nonspecific interactions. All together, we suggest that cMBP2 is a suitable choice for

Covalent attachment of pyridine-type molecules to glassy carbon surfaces by electrochemical reduction of in situ generated diazonium salts. Formation of ruthenium complexes on ligand-modified surfaces

Energy Technology Data Exchange (ETDEWEB)

Yesildag, Ali [Department of Chemistry, Faculty of Sciences, Atatuerk University, 25240 Erzurum (Turkey); Ekinci, Duygu, E-mail: dekin@atauni.edu.t [Department of Chemistry, Faculty of Sciences, Atatuerk University, 25240 Erzurum (Turkey)

2010-09-30

In this study, pyridine, quinoline and phenanthroline molecules were covalently bonded to glassy carbon (GC) electrode surfaces for the first time using the diazonium modification method. Then, the complexation ability of the modified films with ruthenium metal cations was investigated. The derivatization of GC surfaces with heteroaromatic molecules was achieved by electrochemical reduction of the corresponding in situ generated diazonium salts. X-ray photoelectron spectroscopy (XPS) was used to confirm the attachment of heteroaromatic molecules to the GC surfaces and to determine the surface concentration of the films. The barrier properties of the modified GC electrodes were studied in the presence of redox probes such as Fe(CN){sub 6}{sup 3-} and Ru(NH{sub 3}){sub 6}{sup 3+} by cyclic voltammetry. Additionally, the presence of the resulting organometallic films on the surfaces was verified by XPS after the chemical transformation of the characterized ligand films to the ruthenium complex films. The electrochemical behavior of these films in acetonitrile solution was investigated using voltammetric methods, and the surface coverage of the organometallic films was determined from the reversible metal-based Ru(II)/Ru(III) oxidation waves.

Electrical and Plasmonic Properties of Ligand-Free Sn(4+) -Doped In2 O3 (ITO) Nanocrystals.

Science.gov (United States)

Jagadeeswararao, Metikoti; Pal, Somnath; Nag, Angshuman; Sarma, D D

2016-03-03

Sn(4+) -doped In2 O3 (ITO) is a benchmark transparent conducting oxide material. We prepared ligand-free but colloidal ITO (8 nm, 10 % Sn(4+) ) nanocrystals (NCs) by using a post-synthesis surface-modification reaction. (CH3 )3 OBF4 removes the native oleylamine ligand from NC surfaces to give ligand-free, positively charged NCs that form a colloidal dispersion in polar solvents. Both oleylamine-capped and ligand-free ITO NCs exhibit intense absorption peaks, due to localized surface plasmon resonance (LSPR) at around λ=1950 nm. Compared with oleylamine-capped NCs, the electrical resistivity of ligand-free ITO NCs is lower by an order of magnitude (≈35 mΩ cm(-1) ). Resistivity over a wide range of temperatures can be consistently described as a composite of metallic ITO grains embedded in an insulating matrix by using a simple equivalent circuit, which provides an insight into the conduction mechanism in these systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Measuring the Valence of Nanocrystal Surfaces

Energy Technology Data Exchange (ETDEWEB)

Owen, Jonathan Scharle [Columbia Univ., New York, NY (United States)

2016-11-30

The goal of this project is to understand and control the interplay between nanocrystal stoichiometry, surface ligand binding and exchange, and the optoelectronic properties of semiconductor nanocrystals in solution and in thin solid films. We pursued three research directions with this goal in mind: 1) We characterized nanocrystal stoichiometry and its influence on the binding of L-type and X-type ligands, including the thermodynamics of binding and the kinetics of ligand exchange. 2) We developed a quantitative understanding of the relationship between surface ligand passivation and photoluminescence quantum yield. 3) We developed methods to replace the organic ligands on the nanocrystal with halide ligands and controllably deposit these nanocrystals into thin films, where electrical measurements were used to investigate the electrical transport and internanocrystal electronic coupling.

Micro+nanotexturing of substrates to enhance ligand-assisted cancer cell isolation

International Nuclear Information System (INIS)

Mahmood, Mohammed Arif I; Islam, Muhymin; Ali, Waqas; Hanif, Madiha; Iqbal, Samir M; Wan, Yuan; Kim, Young-tae

2014-01-01

This paper presents a simple approach to create a two-tiered surface for superior cancer cell isolation. The idea is inspired by the interactions of cells with a nanotextured basement membrane. The texture mimicked the extracellular matrix and basement membrane for superior target cell adhesion. Prepared micro+nanotextured surfaces showed enhanced cell capture. Preparation of the two-tiered surface was done using micro- and nanotexturing and was easily reproducible. It has been shown before that the larger surface area of a nanotextured surface assists the cell’s attachment through surface-anchored ligands. Taking it a step further, ligand functionalized two-level micro+nanotextured surfaces improved the sensitivity of the cancer cell isolation over simple flat nanotexturing. The isolation efficiency increased by 208% compared to the surface with a single-level nanotexture. The two-tiered surface was compatible with previously reported nanotextured devices used for cancer cell isolation. Micro-texture on the glass surface was created using simple sand gritting, followed by reactive ion etching (RIE) of the entire surface. The approach could create large surface areas within a short time while maintaining superior cell isolation efficiency. (paper)

A conserved WW domain-like motif regulates invariant chain-dependent cell-surface transport of the NKG2D ligand ULBP2

DEFF Research Database (Denmark)

Uhlenbrock, Franziska Katharina; van Andel, Esther; Andresen, Lars

2015-01-01

that the NKG2D ligand ULBP2 traffics over an invariant chain (Ii)-dependent pathway to the cell surface. This study set out to elucidate how Ii regulates ULBP2 cell-surface transport: We discovered conserved tryptophan (Trp) residues in the primary protein sequence of ULBP1-6 but not in the related MICA....../B. Substitution of Trp to alanine resulted in cell-surface inhibition of ULBP2 in different cancer cell lines. Moreover, the mutated ULBP2 constructs were retained and not degraded inside the cell, indicating a crucial role of this conserved Trp-motif in trafficking. Finally, overexpression of Ii increased...... surface expression of wt ULBP2 while Trp-mutants could not be expressed, proposing that this Trp-motif is required for an Ii-dependent cell-surface transport of ULBP2. Aberrant soluble ULBP2 is immunosuppressive. Thus, targeting a distinct protein module on the ULBP2 sequence could counteract...

Ligand-tailored single-site silica supported titanium catalysts: Synthesis, characterization and towards cyanosilylation reaction

International Nuclear Information System (INIS)

Xu, Wei; Li, Yani; Yu, Bo; Yang, Jindou; Zhang, Ying; Chen, Xi; Zhang, Guofang; Gao, Ziwei

2015-01-01

A successive anchoring of Ti(NMe 2 ) 4 , cyclopentadiene and a O-donor ligand, 1-hydroxyethylbenzene (PEA), 1,1′-bi-2-naphthol (Binol) or 2,3-dihydroxybutanedioic acid diethyl ester (Tartrate), on silica was conducted by SOMC strategy in moderate conditions. The silica, monitored by in-situ Fourier transform infrared spectroscopy (in-situ FT-IR), was pretreated at different temperatures (200, 500 and 800 °C). The ligand tailored silica-supported titanium complexes were characterized by in-situ FT-IR, 13 C CP MAS-NMR, X-ray photoelectron spectroscopy (XPS), X-ray absorption near edge structure (XANES) and elemental analysis in detail, verifying that the surface titanium species are single sited. The catalytic activity of the ligand tailored single-site silica supported titanium complexes was evaluated by a cyanosilylation of benzaldehyde. The results showed that the catalytic activity is dependent strongly on the dehydroxylation temperatures of silica and the configuration of the ligands. - Graphical abstract: The ligand-tailored silica supported “single site” titanium complexes were synthesized by SOMC strategy and fully characterized. Their catalytic activity were evaluated by benzaldehyde silylcyanation. - Highlights: • Single-site silica supported Ti active species was prepared by SOMC technique. • O-donor ligand tailored Ti surface species was synthesized. • The surface species was characterized by XPS, 13 C CP-MAS NMR, XANES etc. • Catalytic activity of the Ti active species in silylcyanation reaction was evaluated

Ligand-tailored single-site silica supported titanium catalysts: Synthesis, characterization and towards cyanosilylation reaction

Energy Technology Data Exchange (ETDEWEB)

Xu, Wei; Li, Yani; Yu, Bo; Yang, Jindou; Zhang, Ying; Chen, Xi; Zhang, Guofang, E-mail: gfzhang@snnu.edu.cn; Gao, Ziwei, E-mail: zwgao@snnu.edu.cn

2015-01-15

A successive anchoring of Ti(NMe{sub 2}){sub 4}, cyclopentadiene and a O-donor ligand, 1-hydroxyethylbenzene (PEA), 1,1′-bi-2-naphthol (Binol) or 2,3-dihydroxybutanedioic acid diethyl ester (Tartrate), on silica was conducted by SOMC strategy in moderate conditions. The silica, monitored by in-situ Fourier transform infrared spectroscopy (in-situ FT-IR), was pretreated at different temperatures (200, 500 and 800 °C). The ligand tailored silica-supported titanium complexes were characterized by in-situ FT-IR, {sup 13}C CP MAS-NMR, X-ray photoelectron spectroscopy (XPS), X-ray absorption near edge structure (XANES) and elemental analysis in detail, verifying that the surface titanium species are single sited. The catalytic activity of the ligand tailored single-site silica supported titanium complexes was evaluated by a cyanosilylation of benzaldehyde. The results showed that the catalytic activity is dependent strongly on the dehydroxylation temperatures of silica and the configuration of the ligands. - Graphical abstract: The ligand-tailored silica supported “single site” titanium complexes were synthesized by SOMC strategy and fully characterized. Their catalytic activity were evaluated by benzaldehyde silylcyanation. - Highlights: • Single-site silica supported Ti active species was prepared by SOMC technique. • O-donor ligand tailored Ti surface species was synthesized. • The surface species was characterized by XPS, {sup 13}C CP-MAS NMR, XANES etc. • Catalytic activity of the Ti active species in silylcyanation reaction was evaluated.

Two novel mixed-ligand complexes containing organosulfonate ligands.

Science.gov (United States)

Li, Mingtian; Huang, Jun; Zhou, Xuan; Fang, Hua; Ding, Liyun

2008-07-01

The structures reported herein, viz. bis(4-aminonaphthalene-1-sulfonato-kappaO)bis(4,5-diazafluoren-9-one-kappa(2)N,N')copper(II), [Cu(C(10)H(8)NO(3)S)(2)(C(11)H(6)N(2)O)(2)], (I), and poly[[[diaquacadmium(II)]-bis(mu-4-aminonaphthalene-1-sulfonato)-kappa(2)O:N;kappa(2)N:O] dihydrate], {[Cd(C(10)H(8)NO(3)S)(2)(H(2)O)(2)].2H(2)O}(n), (II), are rare examples of sulfonate-containing complexes where the anion does not fulfill a passive charge-balancing role, but takes an active part in coordination as a monodentate and/or bridging ligand. Monomeric complex (I) possesses a crystallographic inversion center at the Cu(II) atom, and the asymmetric unit contains one-half of a Cu atom, one complete 4-aminonaphthalene-1-sulfonate (ans) ligand and one 4,5-diazafluoren-9-one (DAFO) ligand. The Cu(II) atom has an elongated distorted octahedral coordination geometry formed by two O atoms from two monodentate ans ligands and by four N atoms from two DAFO molecules. Complex (II) is polymeric and its crystal structure is built up by one-dimensional chains and solvent water molecules. Here also the cation (a Cd(II) atom) lies on a crystallographic inversion center and adopts a slightly distorted octahedral geometry. Each ans anion serves as a bridging ligand linking two Cd(II) atoms into one-dimensional infinite chains along the [010] direction, with each Cd(II) center coordinated by four ans ligands via O and N atoms and by two aqua ligands. In both structures, there are significant pi-pi stacking interactions between adjacent ligands and hydrogen bonds contribute to the formation of two- and three-dimensional networks.

Comparative metabolomics reveals endogenous ligands of DAF-12, a nuclear hormone receptor regulating C. elegans development and lifespan

Science.gov (United States)

Mahanti, Parag; Bose, Neelanjan; Bethke, Axel; Judkins, Joshua C.; Wollam, Joshua; Dumas, Kathleen J.; Zimmerman, Anna M.; Campbell, Sydney L.; Hu, Patrick J.; Antebi, Adam; Schroeder, Frank C.

2014-01-01

SUMMARY Small-molecule ligands of nuclear hormone receptors (NHRs) govern the transcriptional regulation of metazoan development, cell differentiation, and metabolism. However, the physiological ligands of many NHRs remain poorly characterized primarily due to lack of robust analytical techniques. Using comparative metabolomics, we identified endogenous steroids that act as ligands of the C. elegans NHR, DAF-12, a vitamin-D and liver-X receptor homolog regulating larval development, fat metabolism, and lifespan. The identified molecules feature unexpected chemical modifications and include only one of two DAF-12 ligands reported earlier, necessitating a revision of previously proposed ligand biosynthetic pathways. We further show that ligand profiles are regulated by a complex enzymatic network including the Rieske oxygenase DAF-36, the short-chain dehydrogenase DHS-16, and the hydroxysteroid dehydrogenase, HSD-1. Our results demonstrate the advantages of comparative metabolomics over traditional candidate-based approaches and provide a blueprint for the identification of ligands for other C. elegans and mammalian NHRs. PMID:24411940

Molecualr-scale multicoordinating ligands for coating luminescent QDs and gold nanoparticles

Science.gov (United States)

Zhan, Naiqian

Colloidal semiconductor quantum dots (QDs) are inorganic nanocrystals that possess several unique photophysical properties, including tunable narrow emission and remarkable photo- and chemical stability. They have large surface area, and thus can be decorated with large numbers and a variety of molecular vectors. These properties combined offer a potentially superior alternative to traditional organic fluorophore for advanced applications in bio-imaging and bio-sensing. Herein, our effort has centered on developing a series of metal coordinating ligands with controllable structures to modify the QD surfaces and construct biocompatible nanocrystals. The ligand architecture accounts for several factors: (i) variable coordination number, (ii) nature of the hydrophilic moiety, polyethylene glycol (PEG) or zwitterion, and (iii) versatility of end-reactive groups including amine, azide, carboxylic acid and aldehyde. The ligand design is combined with a newly developed photoligation strategy to promote the dispersion of luminescent QDs in buffer media. The dissertation is organized in six chapters: In chapter 1, we provide a brief introduction of the basic photophysical properties of QDs and the synthesis history for growing high quality semiconductor nanocrystals. We also present some of the most effective methods reported to date to prepare aqueous QD dispersions, discuss the effective chemical coupling strategies for conjugating biomolecules, and review the recent literatures that have used QD-bioconjugates for imaging and sensing purposes. In Chapter 2, we describe a novel photoligation strategy to promote the transfer of luminescent QDs from hydrophobic to hydrophilic media using lipic acid (LA)-based ligands. We also discusse the experimental conditions, mechanismfor in-situ ligand exchange and the generosity of the method towards the diverse functionality while maintaining the optical properties of the nanocrystals. In chapter 3, we present the design and synthesis

Organic ligand-induced dissolution kinetics of antimony trioxide.

Science.gov (United States)

Hu, Xingyun; He, Mengchang

2017-06-01

The influence of low-molecular-weight dissolved organic matter (LMWDOM) on the dissolution rate of Sb 2 O 3 was investigated. Some representative LMWDOMs with carboxyl, hydroxyl, hydrosulfuryl and amidogen groups occurring naturally in the solution were chosen, namely oxalic acid, citric acid, tartaric acid, EDTA, salicylic acid, phthalandione, glycine, thiolactic acid, xylitol, glucose and catechol. These LMWDOMs were dissolved in inert buffers at pH=3.7, 6.6 and 8.6 and added to powdered Sb 2 O 3 in a stirred, thermostatted reactor (25°C). The addition of EDTA, tartaric acid, thiolactic acid, citric acid and oxalic acid solutions at pH3.7 and catechol at pH8.6 increased the rate of release of antimony. In the 10mmol/L thiolactic acid solution, up to 97% by mass of the antimony was released after 120min reaction. There was no effect on the dissolution of Sb 2 O 3 for the other ligands. A weak correlation between dissolution rate with the dissociation constant of ligands and the stability of the dissolved complex was also found. All the results showed that the extent of the promoting effect of ligands on the dissolution of Sb 2 O 3 was not determined by the stability of the dissolved complex, but by the dissociation constant of ligands and detachment rate of surface chelates from the mineral surface. This study can not only help in further understanding the effect of individual low-molecular-weight organic ligands, but also provides a reference to deduce the effect of natural organic matters with oxygen-bearing functional groups on the dissolution of antimony oxide minerals. Copyright © 2016. Published by Elsevier B.V.

Anatase nanoparticles surface modified with fused ring salicylate-type ligands (1-hydroxy-2-naphthoic acids): A combined DFT and experimental study

Energy Technology Data Exchange (ETDEWEB)

Savić, Tatjana D.; Čomor, Mirjana I.; Abazović, Nadica D.; Šaponjić, Zoran V.; Marinović-Cincović, Milena T. [University of Belgrade, Vinča Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade (Serbia); Veljković, Dušan Ž.; Zarić, Snežana D. [Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11058 Belgrade (Serbia); Janković, Ivana A., E-mail: ivanaj@vinca.rs [University of Belgrade, Vinča Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade (Serbia)

2015-05-05

Highlights: • Formation of the charge-transfer complexes results in a red shift of the TiO{sub 2} absorption. • Extended aromatic ring systems reduce the effective bang gap. • For the CT complexes formed stability constants in the order 10{sup 3} M{sup −1} were determined. • Binding was found to be through bidentate binuclear-bridging complexes. • Ligands interact with different active sites on the TiO{sub 2} surface that express energetic heterogeneity. - Abstract: Sensitization of TiO{sub 2} crystals and nanoparticles with appropriately chosen organic molecules can lead to a significant shift of their absorption threshold from the UV to the visible, thus improving the absorption of the solar spectrum as well as the efficiency of photocatalytic and photovoltaic devices. Herein, the surface modification of nanocrystalline TiO{sub 2} particles (45 Å) with salicylate-type ligands consisting of an extended aromatic ring system, specifically 1-hydroxy-2-naphthoic acid and 1,4-dihydroxy-2-naphthoic acid, was found to alter the optical properties of nanoparticles in a similar way to salicylic acid. From both absorption measurements and steady-state quenching measurements of modifier fluorescence upon binding to TiO{sub 2} in methanol/water = 90/10 solutions, stability constants in the order of 10{sup 3} M{sup −1} have been determined at pH 2. Fluorescence lifetime measurements, in the presence and absence of colloidal TiO{sub 2} nanoparticles, indicated that the fluorescence quenching process is primarily static quenching, thus proving the formation of a nonfluorescent charge-transfer (CT) complex. The binding structures were investigated by using FTIR spectroscopy. Thermal stability of CT-complexes was investigated by using TPD analysis (TG/DTA/MS). Quantum chemical calculations on model systems using density functional theory (DFT) were performed to obtain the vibrational frequencies of charge transfer complexes, and the calculated values were compared

Ligand and membrane-binding behavior of the phosphatidylinositol transfer proteins PITPα and PITPβ.

Science.gov (United States)

Baptist, Matilda; Panagabko, Candace; Cockcroft, Shamshad; Atkinson, Jeffrey

2016-12-01

Phosphatidylinositol transfer proteins (PITPs) are believed to be lipid transfer proteins because of their ability to transfer either phosphatidylinositol (PI) or phosphatidylcholine (PC) between membrane compartments, in vitro. However, the detailed mechanism of this transfer process is not fully established. To further understand the transfer mechanism of PITPs we examined the interaction of PITPs with membranes using dual polarization interferometry (DPI), which measures protein binding affinity on a flat immobilized lipid surface. In addition, a fluorescence resonance energy transfer (FRET)-based assay was also employed to monitor how quickly PITPs transfer their ligands to lipid vesicles. DPI analysis revealed that PITPβ had a higher affinity to membranes compared with PITPα. Furthermore, the FRET-based transfer assay revealed that PITPβ has a higher ligand transfer rate compared with PITPα. However, both PITPα and PITPβ demonstrated a preference for highly curved membrane surfaces during ligand transfer. In other words, ligand transfer rate was higher when the accepting vesicles were highly curved.

Explicit all-atom modeling of realistically sized ligand-capped nanocrystals

KAUST Repository

Kaushik, Ananth P.

2012-01-01

We present a study of an explicit all-atom representation of nanocrystals of experimentally relevant sizes (up to 6 nm), capped with alkyl chain ligands, in vacuum. We employ all-atom molecular dynamics simulation methods in concert with a well-tested intermolecular potential model, MM3 (molecular mechanics 3), for the studies presented here. These studies include determining the preferred conformation of an isolated single nanocrystal (NC), pairs of isolated NCs, and (presaging studies of superlattice arrays) unit cells of NC superlattices. We observe that very small NCs (3 nm) behave differently in a superlattice as compared to larger NCs (6 nm and above) due to the conformations adopted by the capping ligands on the NC surface. Short ligands adopt a uniform distribution of orientational preferences, including some that lie against the face of the nanocrystal. In contrast, longer ligands prefer to interdigitate. We also study the effect of changing ligand length and ligand coverage on the NCs on the preferred ligand configurations. Since explicit all-atom modeling constrains the maximum system size that can be studied, we discuss issues related to coarse-graining the representation of the ligands, including a comparison of two commonly used coarse-grained models. We find that care has to be exercised in the choice of coarse-grained model. The data provided by these realistically sized ligand-capped NCs, determined using explicit all-atom models, should serve as a reference standard for future models of coarse-graining ligands using united atom models, especially for self-assembly processes. © 2012 American Institute of Physics.

AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms

Science.gov (United States)

Ravindranath, Pradeep Anand; Sanner, Michel F.

2016-01-01

Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: http://adfr.scripps.edu/AutoDockFR/autosite.html Contact: sanner@scripps.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

The relative importance of topography and RGD ligand density for endothelial cell adhesion.

Directory of Open Access Journals (Sweden)

Guillaume Le Saux

Full Text Available The morphology and function of endothelial cells depends on the physical and chemical characteristics of the extracellular environment. Here, we designed silicon surfaces on which topographical features and surface densities of the integrin binding peptide arginine-glycine-aspartic acid (RGD could be independently controlled. We used these surfaces to investigate the relative importance of the surface chemistry of ligand presentation versus surface topography in endothelial cell adhesion. We compared cell adhesion, spreading and migration on surfaces with nano- to micro-scaled pyramids and average densities of 6×10(2-6×10(11 RGD/mm(2. We found that fewer cells adhered onto rough than flat surfaces and that the optimal average RGD density for cell adhesion was 6×10(5 RGD/mm(2 on flat surfaces and substrata with nano-scaled roughness. Only on surfaces with micro-scaled pyramids did the topography hinder cell migration and a lower average RGD density was optimal for adhesion. In contrast, cell spreading was greatest on surfaces with 6×10(8 RGD/mm(2 irrespectively of presence of feature and their size. In summary, our data suggest that the size of pyramids predominately control the number of endothelial cells that adhere to the substratum but the average RGD density governs the degree of cell spreading and length of focal adhesion within adherent cells. The data points towards a two-step model of cell adhesion: the initial contact of cells with a substratum may be guided by the topography while the engagement of cell surface receptors is predominately controlled by the surface chemistry.

Ligand receptor dynamics at streptavidin-coated particle surfaces: A flow cytometric and spectrofluorimetric study

Energy Technology Data Exchange (ETDEWEB)

Buranda, T. [Univ. of New Mexico School of Medicine, Albuquerque, NM (United States)]|[Univ. of New Mexico, Albuquerque, NM (United States); Jones, G.M. [Univ. of New Mexico School of Medicine, Albuquerque, NM (United States); Nolan, J.P.; Keij, J. [Los Alamos National Labs., NM (United States); Lopez, G.P. [Univ. of New Mexico, Albuquerque, NM (United States); Sklar, L.A. [Univ. of New Mexico School of Medicine, Albuquerque, NM (United States)]|[Los Alamos National Lab., NM (United States)

1999-04-29

The authors have studied the binding of 5-((N-(5-(N-(6-(biotinoyl)amino)hexanoyl)amino)pentyl)thioureidyl)fluorescein (fluorescein biotin) to 6.2 {micro}m diameter, streptavidin-coated polystyrene beads using a combination of fluorimetric and flow cytometric methods. They have determined the average number of binding sites per bead, the extent of fluorescein quenching upon binding to the bead, and the association and dissociation kinetics. The authors estimate the site number to be {approx}1 million per bead. The binding of the fluorescein biotin ligand occurs in steps where the insertion of the biotin moiety into one receptor pocket is followed immediately by the capture of the fluorescein moiety by a neighboring binding pocket; fluorescence quenching is a consequence of this secondary binding. At high surface coverage, the dominant mechanism of quenching appears to be via the formation of nonfluorescent nearest-neighbor aggregates. At early times, the binding process is characterized by biphasic association and dissociation kinetics which are remarkably dependent on the initial concentration of the ligand. The rate constant for binding to the first receptor pocket of a streptavidin molecule is {approx}(1.3 {+-} 0.3) {times} 10{sup 7} 1{sup {minus}1} S{sup {minus}1}. The rate of binding of a second biotin may be reduced due to steric interference. The early time dissociative behavior is in sharp contrast to the typical stability associated with this system. The early time dissociative behavior is in sharp contrast to the typical stability associated with this system. The dissociation rate constant is as high as 0.05 s{sup {minus}1} shortly after binding, but decreases by 3 orders of magnitude after 3 h of binding. Potential sources for the time dependence of the dissociation rate constant are discussed.

Ligand Depot: a data warehouse for ligands bound to macromolecules.

Science.gov (United States)

Feng, Zukang; Chen, Li; Maddula, Himabindu; Akcan, Ozgur; Oughtred, Rose; Berman, Helen M; Westbrook, John

2004-09-01

Ligand Depot is an integrated data resource for finding information about small molecules bound to proteins and nucleic acids. The initial release (version 1.0, November, 2003) focuses on providing chemical and structural information for small molecules found as part of the structures deposited in the Protein Data Bank. Ligand Depot accepts keyword-based queries and also provides a graphical interface for performing chemical substructure searches. A wide variety of web resources that contain information on small molecules may also be accessed through Ligand Depot. Ligand Depot is available at http://ligand-depot.rutgers.edu/. Version 1.0 supports multiple operating systems including Windows, Unix, Linux and the Macintosh operating system. The current drawing tool works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.

Adsorption of hairy particles with mobile ligands: Molecular dynamics and density functional study

Science.gov (United States)

Borówko, M.; Sokołowski, S.; Staszewski, T.; Pizio, O.

2018-01-01

We study models of hairy nanoparticles in contact with a hard wall. Each particle is built of a spherical core with a number of ligands attached to it and each ligand is composed of several spherical, tangentially jointed segments. The number of segments is the same for all ligands. Particular models differ by the numbers of ligands and of segments per ligand, but the total number of segments is constant. Moreover, our model assumes that the ligands are tethered to the core in such a manner that they can "slide" over the core surface. Using molecular dynamics simulations we investigate the differences in the structure of a system close to the wall. In order to characterize the distribution of the ligands around the core, we have calculated the end-to-end distances of the ligands and the lengths and orientation of the mass dipoles. Additionally, we also employed a density functional approach to obtain the density profiles. We have found that if the number of ligands is not too high, the proposed version of the theory is capable to predict the structure of the system with a reasonable accuracy.

Impact of protein and ligand impurities on ITC-derived protein-ligand thermodynamics.

Science.gov (United States)

Grüner, Stefan; Neeb, Manuel; Barandun, Luzi Jakob; Sielaff, Frank; Hohn, Christoph; Kojima, Shun; Steinmetzer, Torsten; Diederich, François; Klebe, Gerhard

2014-09-01

The thermodynamic characterization of protein-ligand interactions by isothermal titration calorimetry (ITC) is a powerful tool in drug design, giving valuable insight into the interaction driving forces. ITC is thought to require protein and ligand solutions of high quality, meaning both the absence of contaminants as well as accurately determined concentrations. Ligands synthesized to deviating purity and protein of different pureness were titrated by ITC. Data curation was attempted also considering information from analytical techniques to correct stoichiometry. We used trypsin and tRNA-guanine transglycosylase (TGT), together with high affinity ligands to investigate the effect of errors in protein concentration as well as the impact of ligand impurities on the apparent thermodynamics. We found that errors in protein concentration did not change the thermodynamic properties obtained significantly. However, most ligand impurities led to pronounced changes in binding enthalpy. If protein binding of the respective impurity is not expected, the actual ligand concentration was corrected for and the thus revised data compared to thermodynamic properties obtained with the respective pure ligand. Even in these cases, we observed differences in binding enthalpy of about 4kJ⋅mol(-1), which is considered significant. Our results indicate that ligand purity is the critical parameter to monitor if accurate thermodynamic data of a protein-ligand complex are to be recorded. Furthermore, artificially changing fitting parameters to obtain a sound interaction stoichiometry in the presence of uncharacterized ligand impurities may lead to thermodynamic parameters significantly deviating from the accurate thermodynamic signature. Copyright © 2014 Elsevier B.V. All rights reserved.

A feasibility study of unconventional planar ligand spacers in chalcogenide nanocrystals.

Science.gov (United States)

Lukose, Binit; Clancy, Paulette

2016-05-18

The solar cell efficiency of chalcogenide nanocrystals (quantum dots) has been limited in the past by the insulation between neighboring quantum dots caused by intervening, often long-chain, aliphatic ligands. We have conducted a computationally based feasibility study to investigate the use of ultra-thin, planar, charge-conducting ligands as an alternative to traditional long passive ligands. Not only might these radically unconventional ligands decrease the mean distance between adjacent quantum dots, but, since they are charge-conducting, they have the potential to actively enhance charge migration. Our ab initio studies compare the binding energies, electronic energy gaps, and absorption characteristics for both conventional and unconventional ligands, such as phthalocyanines, porphyrins and coronene. This comparison identified these unconventional ligands with the exception of titanyl phthalocyanine, that bind to themselves more strongly than to the surface of the quantum dot, which is likely to be less desirable for enhancing charge transport. The distribution of finite energy levels of the bound system is sensitive to the ligand's binding site and the levels correspond to delocalized states. We also observed a trap state localized on a single Pb atom when a sulfur-containing phenyldithiocarbamate (PTC) ligand is attached to a slightly off-stoichiometric dot in a manner that the sulfur of the ligand completes stoichiometry of the bound system. Hence, this is indicative of the source of trap state when thio-based ligands are bound to chalcogenide nanocrystals. We also predict that titanyl phthalocyanine in a mix with chalcogenide dots of diameter ∼1.5 Å can form a donor-acceptor system.

Ligands in PSI structures

International Nuclear Information System (INIS)

Kumar, Abhinav; Chiu, Hsiu-Ju; Axelrod, Herbert L.; Morse, Andrew; Elsliger, Marc-André; Wilson, Ian A.; Deacon, Ashley

2010-01-01

A survey of the types and frequency of ligands that are bound to PSI structures is analyzed as well as their utility in functional annotation of previously uncharacterized proteins. Approximately 65% of PSI structures report some type of ligand(s) that is bound in the crystal structure. Here, a description is given of how such ligands are handled and analyzed at the JCSG and a survey of the types, variety and frequency of ligands that are observed in the PSI structures is also compiled and analyzed, including illustrations of how these bound ligands have provided functional clues for annotation of proteins with little or no previous experimental characterization. Furthermore, a web server was developed as a tool to mine and analyze the PSI structures for bound ligands and other identifying features

Ligand-Modified Human Serum Albumin Nanoparticles for Enhanced Gene Delivery.

Science.gov (United States)

Look, Jennifer; Wilhelm, Nadine; von Briesen, Hagen; Noske, Nadja; Günther, Christine; Langer, Klaus; Gorjup, Erwin

2015-09-08

The development of nonviral gene delivery systems is a great challenge to enable safe gene therapy. In this study, ligand-modified nanoparticles based on human serum albumin (HSA) were developed and optimized for an efficient gene therapy. Different glutaraldehyde cross-linking degrees were investigated to optimize the HSA nanoparticles for gene delivery. The peptide sequence arginine-glycine-aspartate (RGD) and the HIV-1 transactivator of transduction sequence (Tat) are well-known as promising targeting ligands. Plasmid DNA loaded HSA nanoparticles were covalently modified on their surface with these different ligands. The transfection potential of the obtained plasmid DNA loaded RGD- and Tat-modified nanoparticles was investigated in vitro, and optimal incubation conditions for these preparations were studied. It turned out that Tat-modified HSA nanoparticles with the lowest cross-linking degree of 20% showed the highest transfection potential. Taken together, ligand-functionalized HSA nanoparticles represent promising tools for efficient and safe gene therapy.

Evaluation of a focused virtual library of heterobifunctional ligands for Clostridium difficile toxins.

Science.gov (United States)

Sanhueza, Carlos A; Cartmell, Jonathan; El-Hawiet, Amr; Szpacenko, Adam; Kitova, Elena N; Daneshfar, Rambod; Klassen, John S; Lang, Dean E; Eugenio, Luiz; Ng, Kenneth K-S; Kitov, Pavel I; Bundle, David R

2015-01-07

A focused library of virtual heterobifunctional ligands was generated in silico and a set of ligands with recombined fragments was synthesized and evaluated for binding to Clostridium difficile toxins. The position of the trisaccharide fragment was used as a reference for filtering docked poses during virtual screening to match the trisaccharide ligand in a crystal structure. The peptoid, a diversity fragment probing the protein surface area adjacent to a known binding site, was generated by a multi-component Ugi reaction. Our approach combines modular fragment-based design with in silico screening of synthetically feasible compounds and lays the groundwork for future efforts in development of composite bifunctional ligands for large clostridial toxins.

Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

Directory of Open Access Journals (Sweden)

Tino Wolter

Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

Assessing the effect of dissolved organic ligands on mineral dissolution rates: An example from calcite dissolution

International Nuclear Information System (INIS)

DeMaio, T.; Grandstaff, D.E.

1997-01-01

Experiments suggest that dissolved organic ligands may primarily modify mineral dissolution rates by three mechanisms: (1) metal-ligand (M-L) complex formation in solution, which increases the degree of undersaturation, (2) formation of surface M-L complexes that attack the surface, and (3) formation of surface complexes which passivate or protect the surface. Mechanisms (1) and (2) increase the dissolution rate and the third decreases it compared with organic-free solutions. The types and importance of these mechanisms may be assessed from plots of dissolution rate versus degree of undersaturation. To illustrate this technique, calcite, a common repository cementing and vein-filling mineral, was dissolved at pH 7.8 and 22 C in Na-Ca-HCO 3 -Cl solutions with low concentrations of three organic ligands. Low citrate concentrations (50 microM) increased the dissolution rate consistent with mechanism (1). Oxalate decreased the rate, consistent with mechanism (3). Low phthalate concentration (<50 microM) decreased calcite dissolution rates; however, higher concentrations increased the dissolution rates, which became faster than in inorganic solutions. Thus, phthalate exhibits both mechanisms (2) and (3) at different concentrations. In such cases linear extrapolations of dissolution rates from high organic ligand concentrations may not be valid

Effect of Ligand Exchange on the Photoluminescence Properties of Cu-Doped Zn-In-Se Quantum Dots

Science.gov (United States)

Dong, Xiaofei; Xu, Jianping; Yang, Hui; Zhang, Xiaosong; Mo, Zhaojun; Shi, Shaobo; Li, Lan; Yin, Shougen

2018-04-01

The surface-bound ligands of a semiconductor nanocrystal can affect its electron transition behavior. We investigate the photoluminescence (PL) properties of Cu-doped Zn-In-Se quantum dots (QDs) through the exchange of oleylamine with 6-mercaptohexanol (MCH). Fourier transform infrared and 1H nuclear magnetic resonance spectroscopies, and mass spectrometry reveal that the short-chain MCH molecules are bound to the QD surface. The emission peaks remain unchanged after ligand exchange, and the PL quantum yield is reduced from 49% to 38%. The effects of particle size and defect type on the change in PL behavior upon ligand substitution are excluded through high-resolution transmission electron microscopy, UV-Vis absorption, and PL spectroscopies. The origin of the decreased PL intensity is associated with increased ligand density and the stronger ligand electron-donating abilities of MCH-capped QDs that induce an increase in the nonradiative transition probability. A lower PL quenching transition temperature is observed for MCH-capped QDs and is associated with increasing electron-acoustic phonon coupling due to the lower melting temperature of MCH.

Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

Directory of Open Access Journals (Sweden)

Stéphanie Pérot

Full Text Available Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely

Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

Science.gov (United States)

Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

2013-01-01

Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket

Fundamental Factors Impacting the Stability of Phosphonate-Derivatized Ruthenium Polypyridyl Sensitizers Adsorbed on Metal Oxide Surfaces.

Science.gov (United States)

Raber, McKenzie; Brady, Matthew David; Troian-Gautier, Ludovic; Dickenson, John; Marquard, Seth L; Hyde, Jacob; Lopez, Santiago; Meyer, Gerald J; Meyer, Thomas J; Harrison, Daniel P

2018-06-08

A series of 18 ruthenium(II) polypyridyl complexes were synthesized and evaluated under electrochemically oxidative conditions, which generates the Ru(III) oxidation state and mimics the harsh conditions experienced during the kinetically-limited regime that can occur in dye-sensitized solar cells (DSSCs) and dye-sensitized photoelectrosynthesis cells (DSPECs), to further develop fundamental insights into the factors governing molecular sensitizer surface stability in aqueous 0.1 M HClO4 (aq). Both desorption and oxidatively induced ligand substitution were observed on planar fluorine doped tin oxide, FTO, electrodes, with a dependence on the E1/2 Ru(III/II) redox potential dictating the comparative ratios of the processes. Complexes such as RuP4OMe (E1/2 = 0.91 vs Ag/AgCl) displayed virtually only desorption, while complexes such as RuPbpz (E1/2 > 1.62 V vs Ag/AgCl) displayed only chemical decomposition. Comparing isomers of 4,4'- and 5,5-disubstituted-2,2'-bipyridine ancillary polypyridyl ligands, a dramatic increase in the rate of desorption of the Ru(III) complexes was observed for the 5,5'-ligands. Nanoscopic indium doped tin oxide thin films, nanoITO, were also sensitized and analyzed with cyclic voltammetry, UV-Vis absorption spectroscopy, and XPS, allowing for further distinction of desorption versus ligand substitution processes. Desorption loss to bulk solution associated with the planar surface of FTO is essentially non-existent on nanoITO, where both desorption and ligand substitution are shut down with RuP4OMe. These results revealed that minimizing time spent in the oxidized form, incorporating electron donating groups, maximizing hydrophobicity, and minimizing molecular bulk near the adsorbed ligand are critical to optimizing the performance of ruthenium(II) polypyridyl complexes in dye-sensitized solar cell devices.

Role of ligand-ligand vs. core-core interactions in gold nanoclusters.

Science.gov (United States)

Milowska, Karolina Z; Stolarczyk, Jacek K

2016-05-14

The controlled assembly of ligand-coated gold nanoclusters (NCs) into larger structures paves the way for new applications ranging from electronics to nanomedicine. Here, we demonstrate through rigorous density functional theory (DFT) calculations employing novel functionals accounting for van der Waals forces that the ligand-ligand interactions determine whether stable assemblies can be formed. The study of NCs with different core sizes, symmetry forms, ligand lengths, mutual crystal orientations, and in the presence of a solvent suggests that core-to-core van der Waals interactions play a lesser role in the assembly. The dominant interactions originate from combination of steric effects, augmented by ligand bundling on NC facets, and related to them changes in electronic properties induced by neighbouring NCs. We also show that, in contrast to standard colloidal theory approach, DFT correctly reproduces the surprising experimental trends in the strength of the inter-particle interaction observed when varying the length of the ligands. The results underpin the importance of understanding NC interactions in designing gold NCs for a specific function.

Solution structure of the twelfth cysteine-rich ligand-binding repeat in rat megalin

International Nuclear Information System (INIS)

Wolf, Christian A.; Dancea, Felician; Shi Meichen; Bade-Noskova, Veronika; Rueterjans, Heinz; Kerjaschki, Dontscho; Luecke, Christian

2007-01-01

Megalin, an approx. 600 kDa transmembrane glycoprotein that acts as multi-ligand transporter, is a member of the low density lipoprotein receptor gene family. Several cysteine-rich repeats, each consisting of about 40 residues, are responsible for the multispecific binding of ligands. The solution structure of the twelfth cysteine-rich ligand-binding repeat with class A motif found in megalin features two short β-strands and two helical turns, yielding the typical fold with a I-III, II-V and IV-VI disulfide bridge connectivity pattern and a calcium coordination site at the C-terminal end. The resulting differences in electrostatic surface potential compared to other ligand-binding modules of this gene family, however, may be responsible for the functional divergence

Control of the interparticle spacing in superparamagnetic iron oxide nanoparticle clusters by surface ligand engineering

Science.gov (United States)

Dan, Wang; Bingbing, Lin; Taipeng, Shen; Jun, Wu; Fuhua, Hao; Chunchao, Xia; Qiyong, Gong; Huiru, Tang; Bin, Song; Hua, Ai

2016-07-01

Polymer-mediated self-assembly of superparamagnetic iron oxide (SPIO) nanoparticles allows modulation of the structure of SPIO nanocrystal cluster and their magnetic properties. In this study, dopamine-functionalized polyesters (DA-polyester) were used to directly control the magnetic nanoparticle spacing and its effect on magnetic resonance relaxation properties of these clusters was investigated. Monodisperse SPIO nanocrystals with different surface coating materials (poly(ɛ-caprolactone), poly(lactic acid)) of different molecular weights containing dopamine (DA) structure (DA-PCL2k, DA-PCL1k, DA-PLA1k)) were prepared via ligand exchange reaction, and these nanocrystals were encapsulated inside amphiphilic polymer micelles to modulate the SPIO nanocrystal interparticle spacing. Small-angle x-ray scattering (SAXS) was applied to quantify the interparticle spacing of SPIO clusters. The results demonstrated that the tailored magnetic nanoparticle clusters featured controllable interparticle spacing providing directly by the different surface coating of SPIO nanocrystals. Systematic modulation of SPIO nanocrystal interparticle spacing can regulate the saturation magnetization (M s) and T 2 relaxation of the aggregation, and lead to increased magnetic resonance (MR) relaxation properties with decreased interparticle spacing. Project supported by the National Key Basic Research Program of China (Grant No. 2013CB933903), the National Key Technology R&D Program of China (Grant No. 2012BAI23B08), and the National Natural Science Foundation of China (Grant Nos. 20974065, 51173117, and 50830107).

Ligand-protected gold clusters: the structure, synthesis and applications

Science.gov (United States)

Pichugina, D. A.; Kuz'menko, N. E.; Shestakov, A. F.

2015-11-01

Modern concepts of the structure and properties of atomic gold clusters protected by thiolate, selenolate, phosphine and phenylacetylene ligands are analyzed. Within the framework of the superatom theory, the 'divide and protect' approach and the structure rule, the stability and composition of a cluster are determined by the structure of the cluster core, the type of ligands and the total number of valence electrons. Methods of selective synthesis of gold clusters in solution and on the surface of inorganic composites based, in particular, on the reaction of Aun with RS, RSe, PhC≡C, Hal ligands or functional groups of proteins, on stabilization of clusters in cavities of the α-, β and γ-cyclodextrin molecules (Au15 and Au25) and on anchorage to a support surface (Au25/SiO2, Au20/C, Au10/FeOx) are reviewed. Problems in this field are also discussed. Among the methods for cluster structure prediction, particular attention is given to the theoretical approaches based on the density functional theory (DFT). The structures of a number of synthesized clusters are described using the results obtained by X-ray diffraction analysis and DFT calculations. A possible mechanism of formation of the SR(AuSR)n 'staple' units in the cluster shell is proposed. The structure and properties of bimetallic clusters MxAunLm (M=Pd, Pt, Ag, Cu) are discussed. The Pd or Pt atom is located at the centre of the cluster, whereas Ag and Cu atoms form bimetallic compounds in which the heteroatom is located on the surface of the cluster core or in the 'staple' units. The optical properties, fluorescence and luminescence of ligand-protected gold clusters originate from the quantum effects of the Au atoms in the cluster core and in the oligomeric SR(AuSR)x units in the cluster shell. Homogeneous and heterogeneous reactions catalyzed by atomic gold clusters are discussed in the context of the reaction mechanism and the nature of the active sites. The bibliography includes 345 references.

Phonon Raman spectra of colloidal CdTe nanocrystals: effect of size, non-stoichiometry and ligand exchange

Directory of Open Access Journals (Sweden)

Lokteva Irina

2011-01-01

Full Text Available Abstract Resonant Raman study reveals the noticeable effect of the ligand exchange on the nanocrystal (NC surface onto the phonon spectra of colloidal CdTe NC of different size and composition. The oleic acid ligand exchange for pyridine ones was found to change noticeably the position and width of the longitudinal optical (LO phonon mode, as well as its intensity ratio to overtones. The broad shoulder above the LO peak frequency was enhanced and sharpened after pyridine treatment, as well as with decreasing NC size. The low-frequency mode around 100 cm-1 which is commonly related with the disorder-activated acoustical phonons appears in smaller NCs but is not enhanced after pyridine treatment. Surprisingly, the feature at low-frequency shoulder of the LO peak, commonly assigned to the surface optical phonon mode, was not sensitive to ligand exchange and concomitant close packing of the NCs. An increased structural disorder on the NC surface, strain and modified electron-phonon coupling is discussed as the possible reason of the observed changes in the phonon spectrum of ligand-exchanged CdTe NCs. PACS: 63.20.-e, 78.30.-j, 78.67.-n, 78.67.Bf

Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

International Nuclear Information System (INIS)

Dietz, Marina S; Haße, Daniel; Ferraris, Davide M; Göhler, Antonia; Niemann, Hartmut H; Heilemann, Mike

2013-01-01

The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.

LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

KAUST Repository

Chen, Peng

2014-12-03

Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.

Overview of Stabilizing Ligands for Biocompatible Quantum Dot Nanocrystals

Directory of Open Access Journals (Sweden)

Aaron Clapp

2011-11-01

Full Text Available Luminescent colloidal quantum dots (QDs possess numerous advantages as fluorophores in biological applications. However, a principal challenge is how to retain the desirable optical properties of quantum dots in aqueous media while maintaining biocompatibility. Because QD photophysical properties are directly related to surface states, it is critical to control the surface chemistry that renders QDs biocompatible while maintaining electronic passivation. For more than a decade, investigators have used diverse strategies for altering the QD surface. This review summarizes the most successful approaches for preparing biocompatible QDs using various chemical ligands.

The impact of aminated surface ligands and silica shells on the stability, uptake, and toxicity of engineered silver nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Bonventre, Josephine A.; Pryor, Joseph B.; Harper, Bryan J.; Harper, Stacey L., E-mail: stacey.harper@oregonstate.edu [Oregon State University, Department of Environmental and Molecular Toxicology (United States)

2014-12-15

Inherent nanomaterial characteristics, composition, surface chemistry, and primary particle size, are known to impact particle stability, uptake, and toxicity. Nanocomposites challenge our ability to predict nanoparticle reactivity in biological systems if they are composed of materials with contrasting relative toxicities. We hypothesized that toxicity would be dominated by the nanoparticle surface (shell vs core), and that modulating the surface ligands would have a direct impact on uptake. We exposed developing zebrafish (Danio rerio) to a series of ∼70 nm amine-terminated silver nanoparticles with silica shells (AgSi NPs) to investigate the relative influence of surface amination, composition, and size on toxicity. Like-sized aminated AgSi and Si NPs were more toxic than paired hydroxyl-terminated nanoparticles; however, both AgSi NPs were more toxic than the Si NPs, indicating a significant contribution of the silver core to the toxicity. Incremental increases in surface amination did not linearly increase uptake and toxicity, but did have a marked impact on dispersion stability. Mass-based exposure metrics initially supported the hypothesis that smaller nanoparticles (20 nm) would be more toxic than larger particles (70 nm). However, surface area-based metrics revealed that toxicity was independent of size. Our studies suggest that nanoparticle surfaces play a critical role in the uptake and toxicity of AgSi NPs, while the impact of size may be a function of the exposure metric used. Overall, uptake and toxicity can be dramatically altered by small changes in surface functionalization or exposure media. Only after understanding the magnitude of these changes, can we begin to understand the biologically available dose following nanoparticle exposure.

50-Fold EQE Improvement up to 6.27% of Solution-Processed All-Inorganic Perovskite CsPbBr3 QLEDs via Surface Ligand Density Control.

Science.gov (United States)

Li, Jianhai; Xu, Leimeng; Wang, Tao; Song, Jizhong; Chen, Jiawei; Xue, Jie; Dong, Yuhui; Cai, Bo; Shan, Qingsong; Han, Boning; Zeng, Haibo

2017-02-01

Solution-processed CsPbBr 3 quantum-dot light-emitting diodes with a 50-fold external quantum efficiency improvement (up to 6.27%) are achieved through balancing surface passivation and carrier injection via ligand density control (treating with hexane/ethyl acetate mixed solvent), which induces the coexistence of high levels of ink stability, photoluminescence quantum yields, thin-film uniformity, and carrier-injection efficiency. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organic iron (III) complexing ligands during an iron enrichment experiment in the western subarctic North Pacific

Science.gov (United States)

Kondo, Yoshiko; Takeda, Shigenobu; Nishioka, Jun; Obata, Hajime; Furuya, Ken; Johnson, William Keith; Wong, C. S.

2008-06-01

Complexation of iron (III) with natural organic ligands was investigated during a mesoscale iron enrichment experiment in the western subarctic North Pacific (SEEDS II). After the iron infusions, ligand concentrations increased rapidly with subsequent decreases. While the increases of ligands might have been partly influenced by amorphous iron colloids formation (12-29%), most in-situ increases were attributable to the Dilution of the fertilized patch may have contributed to the rapid decreases of the ligands. During the bloom decline, ligand concentration increased again, and the high concentrations persisted for 10 days. The conditional stability constant was not different between inside and outside of the fertilized patch. These results suggest that the chemical speciation of the released iron was strongly affected by formation of the ligands; the production of ligands observed during the bloom decline will strongly impact the iron cycle and bioavailability in the surface water.

Synthesis and Optical Properties of Thiol Functionalized CdSe/ZnS (Core/Shell Quantum Dots by Ligand Exchange

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Huaping Zhu

2014-01-01

Full Text Available The colloidal photoluminescent quantum dots (QDs of CdSe (core and CdSe/ZnS (core/shell were synthesized at different temperatures with different growth periods. Optical properties (i.e., UV/Vis spectra and photoluminescent emission spectra of the resulting QDs were investigated. The shell-protected CdSe/ZnS QDs exhibited higher photoluminescent (PL efficiency and stability than their corresponding CdSe core QDs. Ligand exchange with various thiol molecules was performed to replace the initial surface passivation ligands, that is, trioctylphosphine oxide (TOPO and trioctylphosphine (TOP, and the optical properties of the surface-modified QDs were studied. The thiol ligand molecules in this study included 1,4-benzenedimethanethiol, 1,16-hexadecanedithiol, 1,11-undecanedithiol, biphenyl-4,4′-dithiol, 11-mercapto-1-undecanol, and 1,8-octanedithiol. After the thiol functionalization, the CdSe/ZnS QDs exhibited significantly enhanced PL efficiency and storage stability. Besides surface passivation effect, such enhanced performance of thiol-functionalized QDs could be due to cross-linked assembly formation of dimer/trimer clusters, in which QDs are linked by dithiol molecules. Furthermore, effects of ligand concentration, type of ligand, and heating on the thiol stabilization of QDs were also discussed.

NKG2D Ligands in Tumor Immunity: Two Sides of a Coin

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Jennifer eWu

2015-03-01

Full Text Available The activating/co-stimulatory receptor NKG2D (natural-killer group 2, member D is expressed on the surface of all human NK, NKT, CD8+ T and subsets of γδ+ T cells. The significance of NKG2D function in tumor immunity has been well demonstrated in experimental animal models. However, the role of human NKG2D ligands in regulating tumor immunity and cancer prognosis had been controversial in the literature. In this review, we summarize the latest advancement, discuss the controversies, and present evidence that membrane-bound and soluble NKG2D ligands oppositely regulate tumor immunity. We also discuss new perspectives of targeting NKG2D ligands for cancer immunotherapy.

Chemogenomic analysis of G-protein coupled receptors and their ligands deciphers locks and keys governing diverse aspects of signalling.

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Jörg D Wichard

Full Text Available Understanding the molecular mechanism of signalling in the important super-family of G-protein-coupled receptors (GPCRs is causally related to questions of how and where these receptors can be activated or inhibited. In this context, it is of great interest to unravel the common molecular features of GPCRs as well as those related to an active or inactive state or to subtype specific G-protein coupling. In our underlying chemogenomics study, we analyse for the first time the statistical link between the properties of G-protein-coupled receptors and GPCR ligands. The technique of mutual information (MI is able to reveal statistical inter-dependence between variations in amino acid residues on the one hand and variations in ligand molecular descriptors on the other. Although this MI analysis uses novel information that differs from the results of known site-directed mutagenesis studies or published GPCR crystal structures, the method is capable of identifying the well-known common ligand binding region of GPCRs between the upper part of the seven transmembrane helices and the second extracellular loop. The analysis shows amino acid positions that are sensitive to either stimulating (agonistic or inhibitory (antagonistic ligand effects or both. It appears that amino acid positions for antagonistic and agonistic effects are both concentrated around the extracellular region, but selective agonistic effects are cumulated between transmembrane helices (TMHs 2, 3, and ECL2, while selective residues for antagonistic effects are located at the top of helices 5 and 6. Above all, the MI analysis provides detailed indications about amino acids located in the transmembrane region of these receptors that determine G-protein signalling pathway preferences.

Nanoparticle-based receptors mimic protein-ligand recognition

OpenAIRE

Riccardi, Laura; Gabrielli, Luca; Sun, Xiaohuan; Biasi, Federico De; Rastrelli, Federico; Mancin, Fabrizio; De Vivo, Marco

2017-01-01

Summary The self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the...

Crystallization of protein–ligand complexes

International Nuclear Information System (INIS)

Hassell, Anne M.; An, Gang; Bledsoe, Randy K.; Bynum, Jane M.; Carter, H. Luke III; Deng, Su-Jun J.; Gampe, Robert T.; Grisard, Tamara E.; Madauss, Kevin P.; Nolte, Robert T.; Rocque, Warren J.; Wang, Liping; Weaver, Kurt L.; Williams, Shawn P.; Wisely, G. Bruce; Xu, Robert; Shewchuk, Lisa M.

2007-01-01

Methods presented for growing protein–ligand complexes fall into the categories of co-expression of the protein with the ligands of interest, use of the ligands during protein purification, cocrystallization and soaking the ligands into existing crystals. Obtaining diffraction-quality crystals has long been a bottleneck in solving the three-dimensional structures of proteins. Often proteins may be stabilized when they are complexed with a substrate, nucleic acid, cofactor or small molecule. These ligands, on the other hand, have the potential to induce significant conformational changes to the protein and ab initio screening may be required to find a new crystal form. This paper presents an overview of strategies in the following areas for obtaining crystals of protein–ligand complexes: (i) co-expression of the protein with the ligands of interest, (ii) use of the ligands during protein purification, (iii) cocrystallization and (iv) soaks

The structure and function of the urokinase receptor, a membrane protein governing plasminogen activation on the cell surface

DEFF Research Database (Denmark)

Behrendt, N; Rønne, E; Danø, K

1995-01-01

PA receptor, uPAR, is a cell-surface protein which plays an important role in the localization and regulation of these processes. In the present article a number of established conclusions concerning the structure and function of uPAR are presented, and in addition various models are discussed which might...... explain additional observations for which the mechanisms involved have not yet been clarified experimentally. uPAR is a highly glycosylated, 3-domain protein, anchored in the plasma membrane by a glycolipid moiety. The domain organization is important for efficient ligand-binding, and the NH2-terminal...

Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens

DEFF Research Database (Denmark)

Andersen, P S; Geisler, C; Buus, S

2001-01-01

Similar to native peptide/MHC ligands, bacterial superantigens have been found to bind with low affinity to the T cell receptor (TCR). It has been hypothesized that low ligand affinity is required to allow optimal TCR signaling. To test this, we generated variants of Staphylococcus enterotoxin C3...... (SEC3) with up to a 150-fold increase in TCR affinity. By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells. Thus, the potency...... correlation between ligand affinity and ligand potency indicating that it is the density of receptor-ligand complexes in the T cell contact area that determines TCR signaling strength....

Surface-environment effects in spin crossover solids

Energy Technology Data Exchange (ETDEWEB)

Gudyma, Iu., E-mail: yugudyma@gmail.com; Maksymov, A.

2017-06-15

Highlights: • The spin-crossover nanocrystals were described by modified Ising-like model. • The ligand field on the surface is a function of external fluctuations. • The thermal hysteresis with surface and bulk interactions of the lattice was studied. • The system behavior with fluctuating ligand field on the surface was examined. • The fluctuations enlarge the hysteresis, but smaller surface interaction narrows it. - Abstract: The impact of surface effects on thermal induced spin crossover phenomenon is a subject of a broad and current interest. Using the modified Ising-like model of spin crossover solids with the ligand field as function of the molecule’ positions and random component on surface by means of Metropolis Monte Carlo algorithm the thermal spin transition curves were calculated. The analysis of spin configuration during transition gives a general idea about contribution of molecules from the surface and inside the lattice into resulting magnetization of the systems. The behavior of hysteresis loop for various surface coupling and fluctuations strength has been described.

Force loading explains spatial sensing of ligands by cells

Science.gov (United States)

Oria, Roger; Wiegand, Tina; Escribano, Jorge; Elosegui-Artola, Alberto; Uriarte, Juan Jose; Moreno-Pulido, Cristian; Platzman, Ilia; Delcanale, Pietro; Albertazzi, Lorenzo; Navajas, Daniel; Trepat, Xavier; García-Aznar, José Manuel; Cavalcanti-Adam, Elisabetta Ada; Roca-Cusachs, Pere

2017-12-01

Cells can sense the density and distribution of extracellular matrix (ECM) molecules by means of individual integrin proteins and larger, integrin-containing adhesion complexes within the cell membrane. This spatial sensing drives cellular activity in a variety of normal and pathological contexts. Previous studies of cells on rigid glass surfaces have shown that spatial sensing of ECM ligands takes place at the nanometre scale, with integrin clustering and subsequent formation of focal adhesions impaired when single integrin-ligand bonds are separated by more than a few tens of nanometres. It has thus been suggested that a crosslinking ‘adaptor’ protein of this size might connect integrins to the actin cytoskeleton, acting as a molecular ruler that senses ligand spacing directly. Here, we develop gels whose rigidity and nanometre-scale distribution of ECM ligands can be controlled and altered. We find that increasing the spacing between ligands promotes the growth of focal adhesions on low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates. Furthermore, disordering the ligand distribution drastically increases adhesion growth, but reduces the rigidity threshold for adhesion collapse. The growth and collapse of focal adhesions are mirrored by, respectively, the nuclear or cytosolic localization of the transcriptional regulator protein YAP. We explain these findings not through direct sensing of ligand spacing, but by using an expanded computational molecular-clutch model, in which individual integrin-ECM bonds—the molecular clutches—respond to force loading by recruiting extra integrins, up to a maximum value. This generates more clutches, redistributing the overall force among them, and reducing the force loading per clutch. At high rigidity and high ligand spacing, maximum recruitment is reached, preventing further force redistribution and leading to adhesion collapse. Measurements of cellular traction forces and actin flow speeds

Secreted and transmembrane 1A is a novel co-stimulatory ligand.

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Duncan Howie

Full Text Available Most T cell responses to pathogens or self antigens are modulated through the action of regulatory T cells and tissue-specific inhibitory mechanisms. To this end, several receptor-ligand pairs have evolved which either augment or diminish T cell function. Here we describe the tissue ligand SECTM1A (Secreted and transmembrane1A as an alternative murine CD7 ligand. We show that SECTM1A, like SECTM1B, binds strongly to CD7, and that SECTM1B was able to compete with SECTM1A for CD7 binding. SECTM1A is ubiquitously expressed and has two major alternative transcripts which differ in expression between tissues. Both immobilised soluble forms of SECTM1A and SECTM1B and cell surface anchored forms demonstrated opposing effects on CD4+ T cell activation. Whereas SECTM1A acted as a co-stimulator of T cells, enhancing IL-2 production and proliferation, SECTM1B proved inhibitory to TCR mediated T cell activation. Surprisingly, both functional outcomes proved to be CD7-independent, indicating the existence of alternative receptors for both ligands. We used a SECTM1A-Fc fusion protein to immunoprecipitate potential alternative ligands from detergent lysates of CD7(-/- T cells and, using mass spectrometry, identified GITR as a SECTM1A binder. SECTM1A was found to bind to activated CD4+ and CD8+ T cells as well as to CHO cells expressing cell surface GITR. Binding of SECTM1A to activated primary T cells was inhibited by either GITRL-Fc or anti GITR antibodies. Thus SECTM1A and SECTM1B represent novel reciprocal alternative ligands which may function to modulate the activation of effector and regulatory T cells. The ability of SECTM1A to activate T cells may be explained by its ability to bind to GITR.

Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites.

Science.gov (United States)

Marsh, Lorraine

2015-01-01

Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorable ΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorable ΔG because of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total binding ΔG arising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein binding region. This metric is essentially a measure of dispersion in equilibrium ligand binding and depends on both the number of potential sites of interaction and the distribution of their individual predicted affinities. Analysis of test cases indicates that, for some ligand/protein pairs involving transporters and carrier proteins, diffuse binding contributes greatly to total affinity, whereas in other cases the influence is modest. This approach may be useful for studying situations where "nonspecific" interactions contribute to biological function.

Inflammation promotes oral squamous carcinoma immune evasion via induced programmed death ligand-1 surface expression.

Science.gov (United States)

Lu, Wanlu; Lu, Libing; Feng, Yun; Chen, Jiao; Li, Yan; Kong, Xiangli; Chen, Sixiu; Li, Xiaoyu; Chen, Qianming; Zhang, Ping

2013-05-01

The association between inflammation and cancer provides a new target for tumor biotherapy. The inflammatory cells and molecules within the tumor microenvironment have decisive dual roles in antitumor immunity and immune evasion. In the present study, phytohemagglutinin (PHA) was used to stimulate peripheral blood mononuclear cells (PBMCs) to simulate the tumor inflammatory microenvironment. The effect of immune cells and inflammatory cytokines on the surface expression of programmed cell death-1 ligand 1 (PD-L1) and tumor immune evasion was investigated using flow cytometry (FCM) and an in vivo xenotransplantation model. Based on the data, PHA-activated, but not resting, immune cells were able to promote the surface expression of PD-L1 in Tca8113 oral squamous carcinoma cells via the secretion of inflammatory cytokines, but not by cell-cell contact. The majority of the inflammatory cytokines had no significant effect on the proliferation, cell cycle progression and apoptosis of the Tca8113 cells, although they each induced the expression of PD-L1 in a dose-dependent manner. In total, 99% of the Tca8113 cells expressed PD-L1 following treatment with the supernatant of PHA-stimulated PBMCs. The PHA-supernatant pretreated Tca8113 cells unusually induced Tca8113 antigen-specific CD8 + T cell apoptosis in vitro and the evasion of antigen-specific T cell attraction in a nude mouse tumor-bearing model. These results indicate a new mechanism for the promotion of tumor immune evasion by the tumor inflammatory microenvironment.

Surface hydrophilicity of PLGA fibers governs in vitro mineralization and osteogenic differentiation

Energy Technology Data Exchange (ETDEWEB)

Thomas, Minnah; Arora, Aditya; Katti, Dhirendra S., E-mail: dsk@iitk.ac.in

2014-12-01

Interfacial properties of biomaterials play an important role in governing their interaction with biological microenvironments. This work investigates the role of surface hydrophilicity of electrospun poly(lactide-co-glycolide) (PLGA) fibers in determining their biological response. For this, PLGA is blended with varying amounts of Pluronic®F-108 and electrospun to fabricate microfibers with varying surface hydrophilicity. The results of mineralization study in simulated body fluid (SBF) demonstrate a significant enhancement in mineralization with an increase in surface hydrophilicity. While presence of serum proteins in SBF reduces absolute mineral content, mineralization continues to be higher on samples with higher surface hydrophilicity. The results from in vitro cell culture studies demonstrate a marked improvement in mesenchymal stem cell —adhesion, elongation, proliferation, infiltration, osteogenic differentiation and matrix mineralization on hydrophilized fibers. Therefore, hydrophilized PLGA fibers are advantageous both in terms of mineralization and elicitation of favorable cell response. Since most of the polymeric materials being used in orthopedics are hydrophobic in nature, the results from this study have strong implications in the future design of interfaces of such hydrophobic materials. In addition, the work proposes a facile method for the modification of electrospun fibers of hydrophobic polymers by blending with a poloxamer for improved bone tissue regeneration. - Highlights: • Surface hydrophilicity of PLGA modulated by blending with Pluronic F-108. • Hydrophilized fibers support better in vitro mineralization. • Mineralization trends retained in the presence of adsorbed serum proteins. • Hydrophilized fibers promote better cell adhesion and proliferation. • Hydrophilized fibers also enable better osteogenic differentiation.

Chiral ligand-protected gold nanoclusters: Considering the optical activity from a viewpoint of ligand dissymmetric field

Directory of Open Access Journals (Sweden)

Hiroshi Yao

2016-10-01

Full Text Available Chirality is a geometric property of a physical, chemical, or biological object, which is not superimposable on its mirror image. Its significant presence has led to a strong demand in the development of chiral drugs, sensors, catalysts, and photofunctional materials. In recent years, chirality of nanoscale organic/inorganic hybrids has received tremendous attention owing to potential applications in chiral nanotechnology. In particular, with the recent progress in the syntheses and characterizations of atomically precise gold nanoclusters protected by achiral thiolates, atomic level origins of their chirality have been unveiled. On the other hand, chirality or optical activity in metal nanoclusters can also be introduced via the surface chiral ligands, which should be universal for the nanosystems. This tutorial review presents some optically-active metal (gold nanoclusters protected by chiral thiolates or phosphines, and their chiroptical (or circular dichroism; CD properties are discussed mostly from a viewpoint of the ligand dissymmetric field scheme. The examples are the gold nanoclusters protected by (R-/(S-2-phenylpropane-1-thiol, (R-/(S-mercaptosuccinic acid, phenylboronate-D/L-fructose complexes, phosphine sulfonate-ephedrinium ion pairs, or glutathione. Some methodologies for versatile asymmetric transformation and chiroptical controls of the nanocluster compounds are also described. In the dissymmetric field model as the origin of optical activity, the chiroptical responses of the gold nanoclusters are strongly associated with coupled oscillator and/or CD stealing mechanisms based on the concept of induced CD (ICD derived from a perturbation theory, so on this basis, some characteristic features of the observed CD responses of chiral ligand-protected gold nanoclusters are presented in detail. We believe that various kinds of origins of chirality found in ligand-protected gold nanoclusters may provide models for understanding those of

LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

KAUST Repository

Chen, Peng; Huang, Jianhua Z; Gao, Xin

2014-01-01

Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction

Identification of ligand-selective peptidic ActRIIB-antagonists using phage display technology

Directory of Open Access Journals (Sweden)

Kotaro Sakamoto

2017-09-01

Full Text Available ActRIIB (activin receptor type-2B is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN, growth differentiation factor 11 (GDF11, and bone morphogenetic protein 9 (BMP9. Notably, the protein-protein interaction (PPI between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia. Here, we report the identification of ligand-selective peptidic ActRIIB-antagonists by phage display technology. Our peptides bound to the extracellular domain of ActRIIB, inhibited PPIs between ActRIIB expressed on the cell surface and its ligands, and subsequently suppressed activation of Smad that serves as the downstream signal of the ActRIIB pathway. Interestingly, these peptidic antagonists displayed different ligand selectivities; the AR2mini peptide inhibited multiple ligands (activin A, MSTN, GDF11, and BMP9, AR9 inhibited MSTN and GDF11, while AR8 selectively inhibited MSTN. This is the first report of artificial peptidic ActRIIB-antagonists possessing ligand-selectivity.

Surface ligand controls silver ion release of nanosilver and its antibacterial activity against Escherichia coli

Directory of Open Access Journals (Sweden)

Long Y

2017-04-01

Full Text Available Yan-Min Long,1,2 Li-Gang Hu,1,3 Xue-Ting Yan,1,3 Xing-Chen Zhao,1,3 Qun-Fang Zhou,1,3 Yong Cai,2,4 Gui-Bin Jiang1,3 1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Beijing, China; 2Institute of Environment and Health, Jianghan University, Wuhan, Hubei, China; 3College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, China; 4Department of Chemistry and Biochemistry, Southeast Environmental Research Center, Florida International University, Miami, FL, USA Abstract: Understanding the mechanism of nanosilver-dependent antibacterial activity against microorganisms helps optimize the design and usage of the related nanomaterials. In this study, we prepared four kinds of 10 nm-sized silver nanoparticles (AgNPs with dictated surface chemistry by capping different ligands, including citrate, mercaptopropionic acid, mercaptohexanoic acid, and mercaptopropionic sulfonic acid. Their surface-dependent chemistry and antibacterial activities were investigated. Owing to the weak bond to surface Ag, short carbon chain, and low silver ion attraction, citrate-coated AgNPs caused the highest silver ion release and the strongest antibacterial activity against Escherichia coli, when compared to the other tested AgNPs. The study on the underlying antibacterial mechanisms indicated that cellular membrane uptake of Ag, NAD+/NADH ratio increase, and intracellular reactive oxygen species (ROS generation were significantly induced in both AgNP and silver ion exposure groups. The released silver ions from AgNPs inside cells through a Trojan-horse-type mechanism were suggested to interact with respiratory chain proteins on the membrane, interrupt intracellular O2 reduction, and induce ROS production. The further oxidative damages of lipid peroxidation and membrane breakdown caused the lethal effect on E. coli. Altogether, this study demonstrated that AgNPs exerted

Adsorbate-induced lifting of substrate relaxation is a general mechanism governing titania surface chemistry.

Science.gov (United States)

Silber, David; Kowalski, Piotr M; Traeger, Franziska; Buchholz, Maria; Bebensee, Fabian; Meyer, Bernd; Wöll, Christof

2016-09-30

Under ambient conditions, almost all metals are coated by an oxide. These coatings, the result of a chemical reaction, are not passive. Many of them bind, activate and modify adsorbed molecules, processes that are exploited, for example, in heterogeneous catalysis and photochemistry. Here we report an effect of general importance that governs the bonding, structure formation and dissociation of molecules on oxidic substrates. For a specific example, methanol adsorbed on the rutile TiO 2 (110) single crystal surface, we demonstrate by using a combination of experimental and theoretical techniques that strongly bonding adsorbates can lift surface relaxations beyond their adsorption site, which leads to a significant substrate-mediated interaction between adsorbates. The result is a complex superstructure consisting of pairs of methanol molecules and unoccupied adsorption sites. Infrared spectroscopy reveals that the paired methanol molecules remain intact and do not deprotonate on the defect-free terraces of the rutile TiO 2 (110) surface.

Versatile gradients of chemistry, bound ligands and nanoparticles on alumina nanopore arrays

International Nuclear Information System (INIS)

Michelmore, Andrew; Poh, Zihan; Goreham, Renee V; Short, Robert D; Vasilev, Krasimir; Mierczynska, Agnieszka; Losic, Dusan

2011-01-01

Nanoporous alumina (PA) arrays produced by self-ordering growth, using electrochemical anodization, have been extensively explored for potential applications based upon the unique thermal, mechanical and structural properties, and high surface-to-volume ratio of these materials. However, the potential applications and functionality of these materials may be further extended by molecular-level engineering of the surface of the pore rims. In this paper we present a method for the generation of chemical gradients on the surface of PA arrays based upon plasma co-polymerization of two monomers. We further extend these chemical gradients, which are also gradients of surface charge, to those of bound ligands and number density gradients of nanoparticles. The latter represent a highly exotic new class of materials, comprising aligned PA, capped by gold nanoparticles around the rim of the pores. Gradients of chemistry, ligands and nanoparticles generated by our method retain the porous structure of the substrate, which is important in applications that take advantage of the inherent properties of these materials. This method can be readily extended to other porous materials.

Versatile gradients of chemistry, bound ligands and nanoparticles on alumina nanopore arrays

Energy Technology Data Exchange (ETDEWEB)

Michelmore, Andrew; Poh, Zihan; Goreham, Renee V; Short, Robert D; Vasilev, Krasimir [Mawson Institute, University of South Australia, Mawson Lakes, SA 5095, Adelaide (Australia); Mierczynska, Agnieszka; Losic, Dusan, E-mail: Krasimir.vasilev@unisa.edu.au [Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Adelaide (Australia)

2011-10-14

Nanoporous alumina (PA) arrays produced by self-ordering growth, using electrochemical anodization, have been extensively explored for potential applications based upon the unique thermal, mechanical and structural properties, and high surface-to-volume ratio of these materials. However, the potential applications and functionality of these materials may be further extended by molecular-level engineering of the surface of the pore rims. In this paper we present a method for the generation of chemical gradients on the surface of PA arrays based upon plasma co-polymerization of two monomers. We further extend these chemical gradients, which are also gradients of surface charge, to those of bound ligands and number density gradients of nanoparticles. The latter represent a highly exotic new class of materials, comprising aligned PA, capped by gold nanoparticles around the rim of the pores. Gradients of chemistry, ligands and nanoparticles generated by our method retain the porous structure of the substrate, which is important in applications that take advantage of the inherent properties of these materials. This method can be readily extended to other porous materials.

Dual-Ligand Modified Polymer-Lipid Hybrid Nanoparticles for Docetaxel Targeting Delivery to Her2/neu Overexpressed Human Breast Cancer Cells.

Science.gov (United States)

Yang, Zhe; Tang, Wenxin; Luo, Xingen; Zhang, Xiaofang; Zhang, Chao; Li, Hao; Gao, Di; Luo, Huiyan; Jiang, Qing; Liu, Jie

2015-08-01

In this study, a dual-ligand polymer-lipid hybrid nanoparticle drug delivery vehicle comprised of an anti-HER2/neu peptide (AHNP) mimic with a modified HIV-1 Tat (mTAT) was established for the targeted treatment of Her2/neu-overexpressing cells. The resultant dual-ligand hybrid nanoparticles (NPs) consisted of a poly(lactide-co-glycolide) core, a near 90% surface coverage of the lipid monolayer, and a 5.7 nm hydrated polyethylene glycol shell. Ligand density optimization study revealed that cellular uptake efficiency of the hybrid NPs could be manipulated by controlling the surface-ligand densities. Furthermore, the cell uptake kinetics and mechanism studies showed that the dual-ligand modifications of hybrid NPs altered the cellular uptake pathway from caveolae-mediated endocytosis (CvME) to the multiple endocytic pathways, which would significantly enhance the NP internalization. Upon the systemic investigation of the cellular uptake behavior of dual-ligand hybrid NPs, docetaxel (DTX), a hydrophobic anticancer drug, was successfully encapsulated into dual-ligand hybrid NPs with high drug loading for Her2/neu-overexpressing SK-BR-3 breast cancer cell treatment. The DTX-loaded dual-ligand hybrid NPs showed a decreased burst release and a more gradual sustained drug release property. Because of the synergistic effect of dual-ligand modification, DTX-loaded dual-ligand hybrid NPs exerted substantially better therapeutic potency against SK-BR-3 cancer cells than other NP formulations and free DTX drugs. These results demonstrate that the dual-ligand hybrid NPs could be a promising vehicle for targeted drug delivery to treat breast cancer.

Field-effect measurements of mobility and carrier concentration of Cu2S colloidal quantum dot thin films after ligand exchange

International Nuclear Information System (INIS)

Brewer, Adam S.; Arnold, Michael S.

2014-01-01

Colloidal quantum dots (CQDs) of copper sulfide (Cu 2 S), an earth-abundant semiconductor, have a number of intriguing applications that require knowledge of their electrical properties. Depending on stoichiometry, mobility, and surface treatment, applications include photoabsorbers for solar cells, tunable plasmonics, and counter-electrodes for polysulfate electrolytes. However, there have not been any direct measurements of electrical properties in Cu 2 S CQD thin films. Here, we exchange as synthesized dodecanethiol ligands with short ethanedithiol or ethylenediamine ligands to form thin films of coupled Cu 2 S CQDs. The mobility and carrier concentration were found to vary by ligand treatment from 10 −5 cm 2 /Vs and 10 19 holes/cm 3 for ethanedithiol ligands to 10 −3 cm 2 /Vs and 10 20 holes/cm 3 for ethylenediamine. These results are consistent with the carrier concentrations inferred from sub-bandgap surface-plasmon-resonances measured by infrared spectroscopy. These results will be useful when designing Cu 2 S materials for future applications. - Highlights: • Colloidal Cu2S quantum dots were synthesized and characterized. • Ligand exchange was performed to alter the Cu2S nanocrystal properties. • Ligand exchange was studied using photoluminescence and infrared spectroscopy. • Field effect mobility and carrier concentration were directly measured. • Carrier concentration was compared to estimates from surface plasmon resonances

Factors governing particulate corrosion product adhesion to surfaces in water reactor coolant circuits

International Nuclear Information System (INIS)

1979-03-01

Gravity, van der Waals, magnetic, electrical double layer and hydrodynamic forces are considered as potential contributors to the adhesion of particulate corrosion products to surfaces in water reactor coolant circuits. These forces are renewed and evaluated, and the following are amongst the conclusions drawn; adequate theories are available to estimate the forces governing corrosion product particle adhesion to surfaces in single phase flow in water reactor coolant circuits. Some uncertainty is introduced by the geometry of real particle-surface systems. The major uncertainties are due to inadequate data on the Hamaker constant and the zeta potential for the relevant materials, water chemistry and radiation chemistry at 300 0 C; van der Waals force is dominant over the effect of gravity for particles smaller than about 100 m; quite modest zeta potentials, approximately 50mV, are capable of inhibiting particle deposition throughout the size range relevant to water reactors; for surfaces exposed to typical water reactor flow conditions, particles smaller than approximately 1 m will be stable against resuspension in the absence of electrical double layer repulsion; and the magnitude of the electrical double layer repulsion for a given potential depends on whether the interaction is assumed to occur at constant potential or constant change. (author)

Water-soluble diphosphadiazacyclooctanes as ligands for aqueous organometallic catalysis

KAUST Repository

Boulanger, Jérôme

2012-12-01

Two new water-soluble diphosphacyclooctanes been synthesized and characterized by NMR and surface tension measurements. Both phosphanes proved to coordinate rhodium in a very selective way as well-defined bidentates were obtained. When used in Rh-catalyzed hydroformylation of terminal alkenes, both ligands positively impacted the reaction chemoselectivity. © 2012 Elsevier B.V.

Water-soluble diphosphadiazacyclooctanes as ligands for aqueous organometallic catalysis

KAUST Repository

Boulanger, Jé rô me; Bricout, Hervé ; Tilloy, Sé bastien; Fihri, Aziz; Len, Christophe; Hapiot, Fré dé ric; Monflier, É ric

2012-01-01

Two new water-soluble diphosphacyclooctanes been synthesized and characterized by NMR and surface tension measurements. Both phosphanes proved to coordinate rhodium in a very selective way as well-defined bidentates were obtained. When used in Rh-catalyzed hydroformylation of terminal alkenes, both ligands positively impacted the reaction chemoselectivity. © 2012 Elsevier B.V.

Bipodal surface organometallic complexes with surface N-donor ligands and application to the catalytic cleavage of C-H and C-C bonds in n -Butane

KAUST Repository

Bendjeriou-Sedjerari, Anissa

2013-11-27

We present a new generation of "true vicinal" functions well-distributed on the inner surface of SBA15: [(Sî - Si-NH 2)(≡Si-OH)] (1) and [(≡Si-NH2)2] (2). From these amine-modified SBA15s, two new well-defined surface organometallic species [(≡Si-NH-)(≡Si-O-)]Zr(CH2tBu) 2 (3) and [(≡Si-NH-)2]Zr(CH2tBu) 2 (4) have been obtained by reaction with Zr(CH2tBu) 4. The surfaces were characterized with 2D multiple-quantum 1H-1H NMR and infrared spectroscopies. Energy-filtered transmission electron microscopy (EFTEM), mass balance, and elemental analysis unambiguously proved that Zr(CH2tBu)4 reacts with these vicinal amine-modified surfaces to give mainly bipodal bis(neopentyl)zirconium complexes (3) and (4), uniformly distributed in the channels of SBA15. (3) and (4) react with hydrogen to give the homologous hydrides (5) and (6). Hydrogenolysis of n-butane catalyzed by these hydrides was carried out at low temperature (100 C) and low pressure (1 atm). While (6) exhibits a bis(silylamido)zirconium bishydride, [(≡Si-NH-)2]Zr(H) 2 (6a) (60%), and a bis(silylamido)silyloxozirconium monohydride, [(≡Si-NH-)2(≡Si-O-)]ZrH (6b) (40%), (5) displays a new surface organometallic complex characterized by an 1H NMR signal at 14.46 ppm. The latter is assigned to a (silylimido)(silyloxo)zirconium monohydride, [(≡Si-Nî)(≡Si-O-)]ZrH (5b) (30%), coexistent with a (silylamido)(silyloxo)zirconium bishydride, [(≡Si-NH-)(≡Si-O-)] Zr(H)2 (5a) (45%), and a silylamidobis(silyloxo)zirconium monohydride, [(≡Si-NH-)(≡Si-O-)2]ZrH (5c) (25%). Surprisingly, nitrogen surface ligands possess catalytic properties already encountered with silicon oxide surfaces, but interestingly, catalyst (5) with chelating [N,O] shows better activity than (6) with chelating [N,N]. © 2013 American Chemical Society.

Bipodal surface organometallic complexes with surface N-donor ligands and application to the catalytic cleavage of C-H and C-C bonds in n -Butane

KAUST Repository

Bendjeriou-Sedjerari, Anissa; Azzi, Joachim; Abou-Hamad, Edy; Anjum, Dalaver H.; Pasha, Fahran A.; Huang, Kuo-Wei; Emsley, Lyndon; Basset, Jean-Marie

2013-01-01

We present a new generation of "true vicinal" functions well-distributed on the inner surface of SBA15: [(Sî - Si-NH 2)(≡Si-OH)] (1) and [(≡Si-NH2)2] (2). From these amine-modified SBA15s, two new well-defined surface organometallic species [(≡Si-NH-)(≡Si-O-)]Zr(CH2tBu) 2 (3) and [(≡Si-NH-)2]Zr(CH2tBu) 2 (4) have been obtained by reaction with Zr(CH2tBu) 4. The surfaces were characterized with 2D multiple-quantum 1H-1H NMR and infrared spectroscopies. Energy-filtered transmission electron microscopy (EFTEM), mass balance, and elemental analysis unambiguously proved that Zr(CH2tBu)4 reacts with these vicinal amine-modified surfaces to give mainly bipodal bis(neopentyl)zirconium complexes (3) and (4), uniformly distributed in the channels of SBA15. (3) and (4) react with hydrogen to give the homologous hydrides (5) and (6). Hydrogenolysis of n-butane catalyzed by these hydrides was carried out at low temperature (100 C) and low pressure (1 atm). While (6) exhibits a bis(silylamido)zirconium bishydride, [(≡Si-NH-)2]Zr(H) 2 (6a) (60%), and a bis(silylamido)silyloxozirconium monohydride, [(≡Si-NH-)2(≡Si-O-)]ZrH (6b) (40%), (5) displays a new surface organometallic complex characterized by an 1H NMR signal at 14.46 ppm. The latter is assigned to a (silylimido)(silyloxo)zirconium monohydride, [(≡Si-Nî)(≡Si-O-)]ZrH (5b) (30%), coexistent with a (silylamido)(silyloxo)zirconium bishydride, [(≡Si-NH-)(≡Si-O-)] Zr(H)2 (5a) (45%), and a silylamidobis(silyloxo)zirconium monohydride, [(≡Si-NH-)(≡Si-O-)2]ZrH (5c) (25%). Surprisingly, nitrogen surface ligands possess catalytic properties already encountered with silicon oxide surfaces, but interestingly, catalyst (5) with chelating [N,O] shows better activity than (6) with chelating [N,N]. © 2013 American Chemical Society.

Ligand-protected gold clusters: the structure, synthesis and applications

International Nuclear Information System (INIS)

Pichugina, D A; Kuz'menko, N E; Shestakov, A F

2015-01-01

Modern concepts of the structure and properties of atomic gold clusters protected by thiolate, selenolate, phosphine and phenylacetylene ligands are analyzed. Within the framework of the superatom theory, the 'divide and protect' approach and the structure rule, the stability and composition of a cluster are determined by the structure of the cluster core, the type of ligands and the total number of valence electrons. Methods of selective synthesis of gold clusters in solution and on the surface of inorganic composites based, in particular, on the reaction of Au n with RS, RSe, PhC≡C, Hal ligands or functional groups of proteins, on stabilization of clusters in cavities of the α-, β and γ-cyclodextrin molecules (Au 15 and Au 25 ) and on anchorage to a support surface (Au 25 /SiO 2 , Au 20 /C, Au 10 /FeO x ) are reviewed. Problems in this field are also discussed. Among the methods for cluster structure prediction, particular attention is given to the theoretical approaches based on the density functional theory (DFT). The structures of a number of synthesized clusters are described using the results obtained by X-ray diffraction analysis and DFT calculations. A possible mechanism of formation of the SR(AuSR) n 'staple' units in the cluster shell is proposed. The structure and properties of bimetallic clusters M x Au n L m (M=Pd, Pt, Ag, Cu) are discussed. The Pd or Pt atom is located at the centre of the cluster, whereas Ag and Cu atoms form bimetallic compounds in which the heteroatom is located on the surface of the cluster core or in the 'staple' units. The optical properties, fluorescence and luminescence of ligand-protected gold clusters originate from the quantum effects of the Au atoms in the cluster core and in the oligomeric SR(AuSR) x units in the cluster shell. Homogeneous and heterogeneous reactions catalyzed by atomic gold clusters are discussed in the context of the reaction mechanism and the nature of the active

A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

KAUST Repository

Li, Huaifeng

2014-12-01

Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands\\' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

KAUST Repository

Li, Huaifeng; Zheng, Bin; Huang, Kuo-Wei

2014-01-01

Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

Light-Emitting Diodes Based on Colloidal Silicon Quantum Dots with Octyl and Phenylpropyl Ligands.

Science.gov (United States)

Liu, Xiangkai; Zhao, Shuangyi; Gu, Wei; Zhang, Yuting; Qiao, Xvsheng; Ni, Zhenyi; Pi, Xiaodong; Yang, Deren

2018-02-14

Colloidal silicon quantum dots (Si QDs) hold ever-growing promise for the development of novel optoelectronic devices such as light-emitting diodes (LEDs). Although it has been proposed that ligands at the surface of colloidal Si QDs may significantly impact the performance of LEDs based on colloidal Si QDs, little systematic work has been carried out to compare the performance of LEDs that are fabricated using colloidal Si QDs with different ligands. Here, colloidal Si QDs with rather short octyl ligands (Octyl-Si QDs) and phenylpropyl ligands (PhPr-Si QDs) are employed for the fabrication of LEDs. It is found that the optical power density of PhPr-Si QD LEDs is larger than that of Octyl-Si QD LEDs. This is due to the fact that the surface of PhPr-Si QDs is more oxidized and less defective than that of Octyl-Si QDs. Moreover, the benzene rings of phenylpropyl ligands significantly enhance the electron transport of QD LEDs. It is interesting that the external quantum efficiency (EQE) of PhPr-Si QD LEDs is lower than that of Octyl-Si QD LEDs because the benzene rings of phenylpropyl ligands suppress the hole transport of QD LEDs. The unbalance between the electron and hole injection in PhPr-Si QD LEDs is more serious than that in Octyl-Si QD LEDs. The currently obtained highest optical power density of ∼0.64 mW/cm 2 from PhPr-Si QD LEDs and highest EQE of ∼6.2% from Octyl-Si QD LEDs should encourage efforts to further advance the development of high-performance optoelectronic devices based on colloidal Si QDs.

Ligand deconstruction: Why some fragment binding positions are conserved and others are not

Science.gov (United States)

Kozakov, Dima; Hall, David R.; Jehle, Stefan; Luo, Lingqi; Ochiana, Stefan O.; Jones, Elizabeth V.; Pollastri, Michael; Allen, Karen N.; Whitty, Adrian; Vajda, Sandor

2015-01-01

Fragment-based drug discovery (FBDD) relies on the premise that the fragment binding mode will be conserved on subsequent expansion to a larger ligand. However, no general condition has been established to explain when fragment binding modes will be conserved. We show that a remarkably simple condition can be developed in terms of how fragments coincide with binding energy hot spots—regions of the protein where interactions with a ligand contribute substantial binding free energy—the locations of which can easily be determined computationally. Because a substantial fraction of the free energy of ligand binding comes from interacting with the residues in the energetically most important hot spot, a ligand moiety that sufficiently overlaps with this region will retain its location even when other parts of the ligand are removed. This hypothesis is supported by eight case studies. The condition helps identify whether a protein is suitable for FBDD, predicts the size of fragments required for screening, and determines whether a fragment hit can be extended into a higher affinity ligand. Our results show that ligand binding sites can usefully be thought of in terms of an anchor site, which is the top-ranked hot spot and dominates the free energy of binding, surrounded by a number of weaker satellite sites that confer improved affinity and selectivity for a particular ligand and that it is the intrinsic binding potential of the protein surface that determines whether it can serve as a robust binding site for a suitably optimized ligand. PMID:25918377

Ligand deconstruction: Why some fragment binding positions are conserved and others are not.

Science.gov (United States)

Kozakov, Dima; Hall, David R; Jehle, Stefan; Jehle, Sefan; Luo, Lingqi; Ochiana, Stefan O; Jones, Elizabeth V; Pollastri, Michael; Allen, Karen N; Whitty, Adrian; Vajda, Sandor

2015-05-19

Fragment-based drug discovery (FBDD) relies on the premise that the fragment binding mode will be conserved on subsequent expansion to a larger ligand. However, no general condition has been established to explain when fragment binding modes will be conserved. We show that a remarkably simple condition can be developed in terms of how fragments coincide with binding energy hot spots--regions of the protein where interactions with a ligand contribute substantial binding free energy--the locations of which can easily be determined computationally. Because a substantial fraction of the free energy of ligand binding comes from interacting with the residues in the energetically most important hot spot, a ligand moiety that sufficiently overlaps with this region will retain its location even when other parts of the ligand are removed. This hypothesis is supported by eight case studies. The condition helps identify whether a protein is suitable for FBDD, predicts the size of fragments required for screening, and determines whether a fragment hit can be extended into a higher affinity ligand. Our results show that ligand binding sites can usefully be thought of in terms of an anchor site, which is the top-ranked hot spot and dominates the free energy of binding, surrounded by a number of weaker satellite sites that confer improved affinity and selectivity for a particular ligand and that it is the intrinsic binding potential of the protein surface that determines whether it can serve as a robust binding site for a suitably optimized ligand.

Ammonia formation by metal-ligand cooperative hydrogenolysis of a nitrido ligand

Science.gov (United States)

Askevold, Bjorn; Nieto, Jorge Torres; Tussupbayev, Samat; Diefenbach, Martin; Herdtweck, Eberhardt; Holthausen, Max C.; Schneider, Sven

2011-07-01

Bioinspired hydrogenation of N2 to ammonia at ambient conditions by stepwise nitrogen protonation/reduction with metal complexes in solution has experienced remarkable progress. In contrast, the highly desirable direct hydrogenation with H2 remains difficult. In analogy to the heterogeneously catalysed Haber-Bosch process, such a reaction is conceivable via metal-centred N2 splitting and unprecedented hydrogenolysis of the nitrido ligands to ammonia. We report the synthesis of a ruthenium(IV) nitrido complex. The high nucleophilicity of the nitrido ligand is demonstrated by unusual N-C coupling with π-acidic CO. Furthermore, the terminal nitrido ligand undergoes facile hydrogenolysis with H2 at ambient conditions to produce ammonia in high yield. Kinetic and quantum chemical examinations of this reaction suggest cooperative behaviour of a phosphorus-nitrogen-phosphorus pincer ligand in rate-determining heterolytic hydrogen splitting.

Reduction of dinitrogen ligands

International Nuclear Information System (INIS)

Richards, R.L.

1983-01-01

Processes of dinitrogen ligand reduction in complexes of transition metals are considered. The basic character of the dinitrogen ligand is underlined. Data on X-ray photoelectronic spectroscopy and intensities of bands ν (N 2 ) in IR-spectra of nitrogen complexes are given. The mechanism of protonation of an edge dinitrogen ligand is discussed. Model systems and mechanism of nitrogenogenase are compared

Beyond the Matrix: The Many Non-ECM Ligands for Integrins

Directory of Open Access Journals (Sweden)

Bryce LaFoya

2018-02-01

Full Text Available The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM, and to a lesser degree, as coordinators of leukocyte adhesion to the endothelium. These canonical activities are indispensable; however, there is also a wide variety of integrin functions mediated by non-ECM ligands that transcend the traditional roles of integrins. Some of these unorthodox roles involve cell-cell interactions and are engaged to support immune functions such as leukocyte transmigration, recognition of opsonization factors, and stimulation of neutrophil extracellular traps. Other cell-cell interactions mediated by integrins include hematopoietic stem cell and tumor cell homing to target tissues. Integrins also serve as cell-surface receptors for various growth factors, hormones, and small molecules. Interestingly, integrins have also been exploited by a wide variety of organisms including viruses and bacteria to support infectious activities such as cellular adhesion and/or cellular internalization. Additionally, the disruption of integrin function through the use of soluble integrin ligands is a common strategy adopted by several parasites in order to inhibit blood clotting during hematophagy, or by venomous snakes to kill prey. In this review, we strive to go beyond the matrix and summarize non-ECM ligands that interact with integrins in order to highlight these non-traditional functions of integrins.

Functional glass slides for in vitro evaluation of interactions between osteosarcoma TE85 cells and mineral-binding ligands

Energy Technology Data Exchange (ETDEWEB)

Song, Jie; Chen, Julia; Klapperich, Catherine M.; Eng, Vincent; Bertozzi, Carolyn R.

2004-07-20

Primary amine-functionalized glass slides obtained through a multi-step plasma treatment were conjugated with anionic amino acids that are frequently found as mineral binding elements in acidic extracellular matrix components of natural bone. The modified glass surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. Human osteosarcoma TE85 cells were cultured on these functionalized slides and analyses on both protein and gene expression levels were performed to probe the ''biocompatibility'' of the surface ligands. Cell attachment and proliferation on anionic surfaces were either better than or comparable to those of cells cultured on tissue culture polystyrene (TCPS). The modified glass surfaces promoted the expression of osteocalcin, alkaline phosphatase activity and ECM proteins such as fibronectin and vitronectin under differentiation culture conditions. Transcript analysis using gene chip microarrays confirmed that culturing TE85 cells on anionic surfaces did not activate apoptotic pathways. Collectively, these results suggest that the potential mineral-binding anionic ligands examined here do not exert significant adverse effects on the expression of important osteogenic markers of TE85 cells. This work paves the way for the incorporation of these ligands into 3-dimensional artificial bone-like scaffolds.

Ligand induced shape transformation of thorium dioxide nanocrystals.

Science.gov (United States)

Wang, Gaoxue; Batista, Enrique R; Yang, Ping

2018-04-27

Nanocrystals (NCs) with size and shape dependent properties are a thriving research field. Remarkable progress has been made in the controlled synthesis of NCs of stable elements in the past two decades; however, the knowledge of the NCs of actinide compounds has been considerably limited due the difficulties in handling them both experimentally and theoretically. Actinide compounds, especially actinide oxides, play a critical role in many stages of the nuclear fuel cycle. Recently, a non-aqueous surfactant assisted approach has been developed for the synthesis of actinide oxide NCs with different morphologies, but an understanding of its control factors is still missing to date. Herein we present a comprehensive study on the low index surfaces of thorium dioxide (ThO2) and their interactions with relevant surfactant ligands using density functional calculations. A systematic picture on the thermodynamic stability of ThO2 NCs of different sizes and shapes is obtained employing empirical models based on the calculated surface energies. It is found that bare ThO2 NCs prefer the octahedral shape terminated by (111) surfaces. Oleic acid displays selective adsorption on the (110) surface, leading to the shape transformation from octahedrons to nanorods. Other ligands such as acetylacetone, oleylamine, and trioctylphosphine oxide do not modify the equilibrium shape of ThO2 NCs. This work provides atomic level insights into the anisotropic growth of ThO2 NCs that was recently observed in experiments, and thus may contribute to the controlled synthesis of actinide oxide NCs with well-defined size and shape for future applications.

Transition Metal Complexes Coordinated by Water Soluble Phosphane Ligands: How Cyclodextrins Can Alter the Coordination Sphere?

Directory of Open Access Journals (Sweden)

Michel Ferreira

2017-01-01

Full Text Available The behaviour of platinum(II and palladium(0 complexes coordinated by various hydrosoluble monodentate phosphane ligands has been investigated by 31P{1H} NMR spectroscopy in the presence of randomly methylated β-cyclodextrin (RAME-β-CD. This molecular receptor can have no impact on the organometallic complexes, induce the formation of phosphane low-coordinated complexes or form coordination second sphere species. These three behaviours are under thermodynamic control and are governed not only by the affinity of RAME-β-CD for the phosphane but also by the phosphane stereoelectronic properties. When observed, the low-coordinated complexes may be formed either via a preliminary decoordination of the phosphane followed by a complexation of the free ligand by the CD or via the generation of organometallic species complexed by CD which then lead to expulsion of ligands to decrease their internal steric hindrance.

Ab initio calculation of transport properties between PbSe quantum dots facets with iodide ligands

Science.gov (United States)

Wang, B.; Patterson, R.; Chen, W.; Zhang, Z.; Yang, J.; Huang, S.; Shrestha, S.; Conibeer, G.

2018-01-01

The transport properties between Lead Selenide (PbSe) quantum dots decorated with iodide ligands has been studied using density functional theory (DFT). Quantum conductance at each selected energy levels has been calculated along with total density of states and projected density of states. The DFT calculation is carried on using a grid-based planar augmented wave (GPAW) code incorporated with the linear combination of atomic orbital (LCAO) mode and Perdew Burke Ernzerhof (PBE) exchange-correlation functional. Three iodide ligand attached low index facets including (001), (011), (111) are investigated in this work. P-orbital of iodide ligand majorly contributes to density of state (DOS) at near top valence band resulting a significant quantum conductance, whereas DOS of Pb p-orbital shows minor influence. Various values of quantum conductance observed along different planes are possibly reasoned from a combined effect electrical field over topmost surface and total distance between adjacent facets. Ligands attached to (001) and (011) planes possess similar bond length whereas it is significantly shortened in (111) plane, whereas transport between (011) has an overall low value due to newly formed electric field. On the other hand, (111) plane with a net surface dipole perpendicular to surface layers leading to stronger electron coupling suggests an apparent increase of transport probability. Apart from previously mentioned, the maximum transport energy levels located several eVs (1 2 eVs) from the edge of valence band top.

Ligand modeling and design

Energy Technology Data Exchange (ETDEWEB)

Hay, B.P. [Pacific Northwest National Lab., Richland, WA (United States)

1997-10-01

The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

A structural view of ligand-dependent activation in thermoTRP channels

Directory of Open Access Journals (Sweden)

Ximena eSteinberg

2014-05-01

Full Text Available Transient Receptor Potential (TRP proteins are a large family of ion channels, grouped intoseven sub-families. Although great advances have been made regarding the activation andmodulation of TRP channel activity, detailed molecular mechanisms governing TRPchannel gating are still needed. Sensitive to electric, chemical, mechanical, and thermalcues, TRP channels are tightly associated with the detection and integration of sensoryinput, emerging as a model to study the polymodal activation of ion channel proteins.Among TRP channels, the temperature-activated kind constitute a subgroup by itself,formed by Vanilloid receptors 1-4, Melastatin receptors 2, 4, 5 and 8, TRPC5, and TRPA1.Some of the so-called thermoTRP channels participate in the detection of noxious stimulimaking them an interesting pharmacological target for the treatment of pain. However, thepoor specificity of the compounds available in the market represents an important obstacleto overcome. Understanding the molecular mechanics underlying ligand-dependentmodulation of TRP channels may help with the rational design of novel syntheticanalgesics. The present review focuses on the structural basis of ligand-dependentactivation of TRPV1 and TRPM8 channels. Special attention is drawn to the dissection ofligand-binding sites within TRPV1, PIP 2 -dependent modulation of TRP channels, and thestructure of natural and synthetic ligands.

Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity*

OpenAIRE

Marty, Caroline; Chaligné, Ronan; Lacout, Catherine; Constantinescu, Stefan N.; Vainchenker, William; Villeval, Jean-Luc

2009-01-01

The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia. MPL belongs to a subset of the cytokine receptor superfamily that requires the JAK2 kinase for signaling. We examined whether the ligand-independent MPLW515L mutant could signal intracellularly. Addition of the endoplasmic reticulum (ER) retention KDEL sequence to the receptor C terminus efficiently locked MPLW515L within its na...

The role of metalloproteinase ADAM17 in regulating ICOS ligand-mediated humoral immune responses

DEFF Research Database (Denmark)

Marczynska, Joanna; Ozga, Aleksandra; Wlodarczyk, Agnieszka

2014-01-01

results in spleen and lymph node enlargement, as well as increased levels of Ag-specific class-switched Ig production following immunization with OVA together with anti-CD40 mAbs and polyinosinic-polycytidylic acid. Moreover, we demonstrate that the costimulatory ligand ICOS ligand (ICOSL) is selectively...... downregulated on the surface of B cells in an ADAM17-specific manner, although it is not proteolitically processed by recombinant ADAM17 in vitro. Finally, we show that higher cell surface levels of ICOSL in ADAM17(ex/ex) mice may contribute to the development of excessive Ab responses. Therefore, our data...... suggest a functional link between ADAM17 and ICOSL in controlling adaptive immune responses....

Ligand identification using electron-density map correlations

International Nuclear Information System (INIS)

Terwilliger, Thomas C.; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

2007-01-01

An automated ligand-fitting procedure is applied to (F o − F c )exp(iϕ c ) difference density for 200 commonly found ligands from macromolecular structures in the Protein Data Bank to identify ligands from density maps. A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F o − F c )exp(iϕ c ) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule

The selenium metabolite methylselenol regulates the expression of ligands that trigger immune activation through the lymphocyte receptor NKG2D

DEFF Research Database (Denmark)

Hagemann-Jensen, Michael Henrik; Uhlenbrock, Franziska Katharina; Kehlet, Stephanie

2014-01-01

For decades Selenium (Se) research has been focused on the identification of active metabolites, which are crucial for Se chemoprevention of cancer. In this context, the metabolite methylselenol (CH3SeH) is known for its action to selectively kill transformed cells through mechanisms that include...... ligands. A balanced cell-surface expression of NKG2D ligands is considered as an innate barrier against tumor development. Our work therefore indicates that the application of selenium compounds, which are metabolized to CH3SeH, could improve NKG2D-based immune therapy.......: Increased formation of reactive oxygen species (ROS), induction of DNA damage, triggering of apoptosis and the inhibition of angiogenesis. Here, we revealed that CH3SeH modulates cell surface expression of NKG2D ligands. The expression of NKG2D ligands is induced by stress-associated pathways, which occur...

Schiff base ligand

Indian Academy of Sciences (India)

Unknown

Low-temperature stoichiometric Schiff base reaction in air in 3 : 1 mole ratio between benz- aldehyde and triethylenetetramine (trien) in methanol yields a novel tetraaza µ-bis(bidentate) acyclic ligand L. It was .... electrochemical work was performed as reported in ..... change in ligand shape through change in oxidation.

Nanoparticle-Based Receptors Mimic Protein-Ligand Recognition.

Science.gov (United States)

Riccardi, Laura; Gabrielli, Luca; Sun, Xiaohuan; De Biasi, Federico; Rastrelli, Federico; Mancin, Fabrizio; De Vivo, Marco

2017-07-13

The self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the monolayer itself and with the solvent. We further describe how the nature and plasticity of these interactions modulate nanoparticle-based chemosensing. Importantly, we found that self-organization of coating thiols can induce the formation of binding pockets in AuNPs. These transient cavities can accommodate small molecules, mimicking protein-ligand recognition, which could explain the selectivity and sensitivity observed for different organic analytes in NMR chemosensing experiments. Thus, our findings advocate for the rational design of tailored coating groups to form specific recognition binding sites on monolayer-protected AuNPs.

ProBiS-ligands: a web server for prediction of ligands by examination of protein binding sites.

Science.gov (United States)

Konc, Janez; Janežič, Dušanka

2014-07-01

The ProBiS-ligands web server predicts binding of ligands to a protein structure. Starting with a protein structure or binding site, ProBiS-ligands first identifies template proteins in the Protein Data Bank that share similar binding sites. Based on the superimpositions of the query protein and the similar binding sites found, the server then transposes the ligand structures from those sites to the query protein. Such ligand prediction supports many activities, e.g. drug repurposing. The ProBiS-ligands web server, an extension of the ProBiS web server, is open and free to all users at http://probis.cmm.ki.si/ligands. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Interaction of calreticulin with CD40 ligand, TRAIL and Fas ligand

DEFF Research Database (Denmark)

Duus, K; Pagh, R T; Holmskov, U

2007-01-01

is utilized by many other functionally diverse molecules and in this work the interaction of calreticulin with C1q and structurally similar molecules was investigated. In addition to C1q and MBL, CD40 ligand (CD40L), tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) were...... found to bind calreticulin strongly. A low level or no binding was observed for adiponectin, tumour necrosis factor-alpha (TNF-alpha), CD30L, surfactant protein-A and -D and collagen VIII. The interaction with calreticulin required a conformational change in CD40L, TRAIL and FasL and showed the same...

Redox Potentials of Ligands and Complexes – a DFT Approach

African Journals Online (AJOL)

NICO

A review of the limited literature concerned with theoretical ways to predict experimentally measured redox potentials of ligands and ... electrode surface, over-potentials and high solvent resistance, ... A correlation coefficient of 0.969 in the linear relation with ... of E0' were performed in two steps, i.e. calculation of the free.

Substituent-directed structural and physicochemical controls of diruthenium catecholate complexes with ligand-unsupported Ru-Ru bonds.

Science.gov (United States)

Chang, Ho-Chol; Mochizuki, Katsunori; Kitagawa, Susumu

2005-05-30

A family of diruthenium complexes with ligand-unsupported Ru-Ru bonds has been systematically synthesized, and their crystal structures and physical properties have been examined. A simple, useful reaction between Ru2(OAc)4Cl (OAc- = acetate) and catechol derivatives in the presence of bases afforded a variety of diruthenium complexes, generally formulated as [Na(n){Ru2(R4Cat)4}] (n = 2 or 3; R4 = -F4, -Cl4, -Br4, -H4, -3,5-di-t-Bu, and -3,6-di-t-Bu; Cat(2-) = catecholate). The most characteristic feature of the complexes is the formation of short ligand-unsupported Ru-Ru bonds (2.140-2.273 A). These comprehensive studies were carried out to evaluate the effects of the oxidation states and the substituents governing the molecular structures and physicochemical properties. The Ru-Ru bond distances, rotational conformations, and bending structures of the complexes were successfully varied. The results presented in this manuscript clearly demonstrate that the complexes with ligand-unsupported Ru-Ru bonds can sensitively respond to redox reactions and ligand substituents on the basis of the greater degree of freedom in their molecular structures.

Beyond Helper Phage: Using "Helper Cells" to Select Peptide Affinity Ligands.

Directory of Open Access Journals (Sweden)

M Lisa Phipps

Full Text Available Peptides are important affinity ligands for microscopy, biosensing, and targeted delivery. However, because they can have low affinity for their targets, their selection from large naïve libraries can be challenging. When selecting peptidic ligands from display libraries, it is important to: 1 ensure efficient display; 2 maximize the ability to select high affinity ligands; and 3 minimize the effect of the display context on binding. The "helper cell" packaging system has been described as a tool to produce filamentous phage particles based on phagemid constructs with varying display levels, while remaining free of helper phage contamination. Here we report on the first use of this system for peptide display, including the systematic characterization and optimization of helper cells, their inefficient use in antibody display and their use in creating and selecting from a set of phage display peptide libraries. Our libraries were analyzed with unprecedented precision by standard or deep sequencing, and shown to be superior in quality than commercial gold standards. Using our helper cell libraries, we have obtained ligands recognizing Yersinia pestis surface antigen F1V and L-glutamine-binding periplasmic protein QBP. In the latter case, unlike any of the peptide library selections described so far, we used a combination of phage and yeast display to select intriguing peptide ligands. Based on the success of our selections we believe that peptide libraries obtained with helper cells are not only suitable, but preferable to traditional phage display libraries for selection of peptidic ligands.

Ligand isotopic exchange of tris(acetylacetonato)germanium(IV) perchlorate in organic solvents

International Nuclear Information System (INIS)

Nagasawa, Akira; Saito, Kazuo

1978-01-01

The ligand isotopic exchange between tris(acetylacetonato)germanium(IV) perchlorate and acetylacetone[ 14 C] has been studied in 1,1,2,2-tetrachloroethane (TCE), nitromethane (NM), and acetonitrile (AN), at 100 - 120 0 C. In these solvents, the rate formula was R = k[H 2 O][complex]; the concentrations of the complex, free ligand, and water in solution were in the ranges from 0.01 to 0.1 mol dm -3 . The activation enthalpies and entropies for the k's are 105, 98, and 90 kJ mol -1 ; and -25, -53, and -69 JK -1 mol -1 , in TCE, NM, and AN, respectively. Influence of acid and base concentrations, and deuterium isotope effect on the rate in AN suggest that the rate controlling step of the exchange is governed by the ease of the proton transfer between the leaving and the incoming acac - in an intermediate. (auth.)

Surface Tension of Multi-phase Flow with Multiple Junctions Governed by the Variational Principle

International Nuclear Information System (INIS)

Matsutani, Shigeki; Nakano, Kota; Shinjo, Katsuhiko

2011-01-01

We explore a computational model of an incompressible fluid with a multi-phase field in three-dimensional Euclidean space. By investigating an incompressible fluid with a two-phase field geometrically, we reformulate the expression of the surface tension for the two-phase field found by Lafaurie et al. (J Comput Phys 113:134–147, 1994) as a variational problem related to an infinite dimensional Lie group, the volume-preserving diffeomorphism. The variational principle to the action integral with the surface energy reproduces their Euler equation of the two-phase field with the surface tension. Since the surface energy of multiple interfaces even with singularities is not difficult to be evaluated in general and the variational formulation works for every action integral, the new formulation enables us to extend their expression to that of a multi-phase (N-phase, N ≥ 2) flow and to obtain a novel Euler equation with the surface tension of the multi-phase field. The obtained Euler equation governs the equation for motion of the multi-phase field with different surface tension coefficients without any difficulties for the singularities at multiple junctions. In other words, we unify the theory of multi-phase fields which express low dimensional interface geometry and the theory of the incompressible fluid dynamics on the infinite dimensional geometry as a variational problem. We apply the equation to the contact angle problems at triple junctions. We computed the fluid dynamics for a two-phase field with a wall numerically and show the numerical computational results that for given surface tension coefficients, the contact angles are generated by the surface tension as results of balances of the kinematic energy and the surface energy.

Regulation of Epithelial Morphogenesis by the G-Protein Coupled Receptor Mist and its Ligand Fog*

Science.gov (United States)

Manning, Alyssa J.; Peters, Kimberly A.; Peifer, Mark; Rogers, Stephen L.

2014-01-01

Epithelial morphogenesis is essential for shaping organs and tissues and for establishment of the three embryonic germ layers during gastrulation. Studies of gastrulation in Drosophila have provided insight into how epithelial morphogenesis is governed by developmental patterning mechanisms. We developed an assay to recapitulate morphogenetic shape changes in individual cultured cells, and used RNAi-based screening to identify Mist, a Drosophila G protein-coupled receptor (GPCR) that transduces signals from the secreted ligand Folded gastrulation (Fog) in cultured cells. Mist functioned in Fog-dependent embryonic morphogenesis, and the transcription factor Snail regulated expression of mist in zygotes. Our data revealed how a cell fate transcriptional program acts through a ligand-GPCR pair to stimulate epithelial morphogenetic shape changes. PMID:24222713

Effect of selected ligands on the U(VI) immobilization by zerovalent iron

International Nuclear Information System (INIS)

Noubactep, C.

2006-01-01

The effect of Cl - , CO 3 2- , EDTA, NO 2 - , NO 3 - , PO 4 3- , SO 4 2- , and humic substances (HS) on the U(VI) co-precipitation from aqueous solutions by zerovalent iron (ZVI) was investigated in the neutral pH range.Batch experiments without shaking were conducted for 14 days mostly with five different ZVI materials (15 g/l), selected ligands (10mM) and an U(VI) solution (20 mg/l, 0.084mM). Apart from Cl - , all tested ligands induced a decrease of U(VI) coprecipitation. This decrease is attributed to the surface adsorption and complexation of the ligands at the reactive sites on the surface of ZVI and their corrosion products. The decrease of U(VI) removal was not uniform with the five ZVI materials. Generally, groundwater with elevated EDTA concentration could not be remediated with the ZVI barrier technology. The response of the system on the pre-treating by two ZVI materials in 250mM HCl indicated that in situ generated corrosion products favor an irreversible U(VI) uptake. Thus for the long term performance of ZVI barrier, the iron dissolution should continue in such a way that fresh iron oxide be always available for U(VI) coprecipitation. (author)

Bitopic Ligands and Metastable Binding Sites

DEFF Research Database (Denmark)

Fronik, Philipp; Gaiser, Birgit I; Sejer Pedersen, Daniel

2017-01-01

of orthosteric binding sites. Bitopic ligands have been employed to address the selectivity problem by combining (linking) an orthosteric ligand with an allosteric modulator, theoretically leading to high-affinity subtype selective ligands. However, it remains a challenge to identify suitable allosteric binding...... that have been reported to date, this type of bitopic ligands would be composed of two identical pharmacophores. Herein, we outline the concept of bitopic ligands, review metastable binding sites, and discuss their potential as a new source of allosteric binding sites....

Sub-20 nm Stable Micelles Based on a Mixture of Coiled-Coils: A Platform for Controlled Ligand Presentation.

Science.gov (United States)

Ang, JooChuan; Ma, Dan; Jung, Benson T; Keten, Sinan; Xu, Ting

2017-11-13

Ligand-functionalized, multivalent nanoparticles have been extensively studied for biomedical applications from imaging agents to drug delivery vehicles. However, the ligand cluster size is usually heterogeneous and the local valency is ill-defined. Here, we present a mixed micelle platform hierarchically self-assembled from a mixture of two amphiphilic 3-helix and 4-helix peptide-polyethylene glycol (PEG)-lipid hybrid conjugates. We demonstrate that the local multivalent ligand cluster size on the micelle surface can be controlled based on the coiled-coil oligomeric state. The oligomeric states of mixed peptide bundles were found to be in their individual native states. Similarly, mixed micelles indicate the orthogonal self-association of coiled-coil amphiphiles. Using differential scanning calorimetry, fluorescence recovery spectroscopy, and coarse-grained molecular dynamics simulation, we studied the distribution of coiled-coil bundles within the mixed micelles and observed migration of coiled-coils into nanodomains within the sub-20 nm mixed micelle. This report provides important insights into the assembly and formation of nanophase-separated micelles with precise control over the local multivalent state of ligands on the micelle surface.

The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator

DEFF Research Database (Denmark)

Behrendt, N; Ploug, M; Patthy, L

1991-01-01

with the internal repeats of u-PAR constitute the extracellular part of Ly-6 antigens and of the squid glycoprotein Sgp-2. Like u-PAR, these proteins are attached to the membrane by a glycosyl-phosphatidylinositol anchor. The hydrophilic, ligand-binding u-PAR domain identified in the present study has potential...

Large-scale binding ligand prediction by improved patch-based method Patch-Surfer2.0.

Science.gov (United States)

Zhu, Xiaolei; Xiong, Yi; Kihara, Daisuke

2015-03-01

Ligand binding is a key aspect of the function of many proteins. Thus, binding ligand prediction provides important insight in understanding the biological function of proteins. Binding ligand prediction is also useful for drug design and examining potential drug side effects. We present a computational method named Patch-Surfer2.0, which predicts binding ligands for a protein pocket. By representing and comparing pockets at the level of small local surface patches that characterize physicochemical properties of the local regions, the method can identify binding pockets of the same ligand even if they do not share globally similar shapes. Properties of local patches are represented by an efficient mathematical representation, 3D Zernike Descriptor. Patch-Surfer2.0 has significant technical improvements over our previous prototype, which includes a new feature that captures approximate patch position with a geodesic distance histogram. Moreover, we constructed a large comprehensive database of ligand binding pockets that will be searched against by a query. The benchmark shows better performance of Patch-Surfer2.0 over existing methods. http://kiharalab.org/patchsurfer2.0/ CONTACT: dkihara@purdue.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Coordination of N,O-donor appended Schiff base ligand (H2L1) towards Zinc(II) in presence of pseudohalides: Syntheses, crystal structures, photoluminescence, antimicrobial activities and Hirshfeld surfaces

Science.gov (United States)

Majumdar, Dhrubajyoti; Biswas, Jayanta Kumar; Mondal, Monojit; Surendra Babu, M. S.; Metre, Ramesh K.; Das, Sourav; Bankura, Kalipada; Mishra, Dipankar

2018-03-01

A series of dinuclear Zn(II) complexes [Zn2 (L1) (CH3OH)2(SCN) (OAc)](1), [Zn2 (L1) (CH3OH)2(N3)2](2) and [Zn2 (L1) (Cl)2(CH3OH)]·CH3OH (3) have been synthesized by the reaction of compartmental Schiff base ligand (H2L1) [N,N‧-Bis(3-ethoxysalicylidenimino)-1,3-diaminopropane] with Zn(OAc)2·2H2O in presence of coligand like KSCN, NaN3 and NaCl respectively. X-ray diffraction analysis revealed that all the complexes are neutral and possess a 4-membered Zn2 (μ2-O)2 ring fastened by the unified coordination action of a doubly deprotonated ligand. In addition, solid state structure of the complexes display extensive intermolecular interaction which has been supported theoretically by Hirshfeld surface analysis with 2D Fingerprint plots. The synthesized Zn(II) metal complexes observed enhancement of luminescence emission compared to the parent Schiff base due to emanating ligand based intraligand (π→π∗) fluorescence. Additionally, Zn(II) metal complexes exhibited considerable antimicrobial potency against some important Gram +ve and Gram -ve bacteria.

Organic-inorganic hybrid perovskite quantum dots with high PLQY and enhanced carrier mobility through crystallinity control by solvent engineering and solid-state ligand exchange.

Science.gov (United States)

Woo Choi, Jin; Woo, Hee Chul; Huang, Xiaoguang; Jung, Wan-Gil; Kim, Bong-Joong; Jeon, Sie-Wook; Yim, Sang-Youp; Lee, Jae-Suk; Lee, Chang-Lyoul

2018-05-22

The photoluminescence quantum yield (PLQY) and charge carrier mobility of organic-inorganic perovskite QDs were enhanced by the optimization of crystallinity and surface passivation as well as solid-state ligand exchange. The crystallinity of perovskite QDs was determined by the Effective solvent field (Esol) of various solvents for precipitation. The solvent with high Esol could more quickly countervail the localized field generated by the polar solvent, and it causes fast crystallization of the dissolved precursor, which results in poor crystallinity. The post-ligand adding process (PLAP) and post-ligand exchange process (PLEP) increase the PLQY of perovskite QDs by reducing non-radiative recombination and the density of surface defect states through surface passivation. Particularly, the post ligand exchange process (PLEP) in the solid-state improved the charge carrier mobility of perovskite QDs in addition to the PLQY enhancement. The ligand exchange with short alkyl chain length ligands could improve the packing density of perovskite QDs in films by reducing the inter-particle distance between perovskite QDs. The maximum hole mobility of 6.2 × 10-3 cm2 V-1 s-1, one order higher than that of pristine QDs without the PLEP, is obtained at perovskite QDs with hexyl ligands. By using PLEP treatment, compared to the pristine device, a 2.5 times higher current efficiency in perovskite QD-LEDs was achieved due to the improved charge carrier mobility and PLQY.

Effect of some environmental ligands and fertilizers on humic acid complexation with strontium. Vol. 4

Energy Technology Data Exchange (ETDEWEB)

Helal, A A; Iman, D M; Khalifa, S M; Aly, H F [Hot Laborities Center, Atomic Energy Authority, Cairo, (Egypt)

1996-03-01

Strontium-90 represents one of the main radionuclides produced in fission products. Migration of strontium in the environment in case of accidental release is governed by many factors, besides its interaction with the materials present in the environment. Both humic acid and fertilizers are present on agricultural lands or aqueous streams. Other ligands such as EDTA, citrates, and phosphates are present in the environment. The binding and exchange of cations by the soil organic fractions is of importance in soil fertility because the supply of Na{sup +}, K{sup +}, Ca{sup 2+}, Mg{sup 2+} and certain micro nutrients (Cu{sup 2+}, Mn{sup 2+}, Zn{sup 2+} and Fe{sup 3+}) to plant is strongly dependent on the cation exchange capacity of the soil which may be induced by organic matters. The effect of the presence of certain fertilizers and some environmental ligands on the Sr-humate complex was studied. In general, the fertilizers and the complexing ligands investigated are compared with humic acid in its complexation with strontium. 6 figs.

Ligand-tailored single-site silica supported titanium catalysts: Synthesis, characterization and towards cyanosilylation reaction

Science.gov (United States)

Xu, Wei; Li, Yani; Yu, Bo; Yang, Jindou; Zhang, Ying; Chen, Xi; Zhang, Guofang; Gao, Ziwei

2015-01-01

A successive anchoring of Ti(NMe2)4, cyclopentadiene and a O-donor ligand, 1-hydroxyethylbenzene (PEA), 1,1‧-bi-2-naphthol (Binol) or 2,3-dihydroxybutanedioic acid diethyl ester (Tartrate), on silica was conducted by SOMC strategy in moderate conditions. The silica, monitored by in-situ Fourier transform infrared spectroscopy (in-situ FT-IR), was pretreated at different temperatures (200, 500 and 800 °C). The ligand tailored silica-supported titanium complexes were characterized by in-situ FT-IR, 13C CP MAS-NMR, X-ray photoelectron spectroscopy (XPS), X-ray absorption near edge structure (XANES) and elemental analysis in detail, verifying that the surface titanium species are single sited. The catalytic activity of the ligand tailored single-site silica supported titanium complexes was evaluated by a cyanosilylation of benzaldehyde. The results showed that the catalytic activity is dependent strongly on the dehydroxylation temperatures of silica and the configuration of the ligands.

Improvement in luminance of light-emitting diode using InP/ZnS quantum dot with 1-dodecanethiol ligand

Science.gov (United States)

Fukuda, Takeshi; Sasaki, Hironao

2018-03-01

We present the synthesis protocol of a red emissive InP/ZnS quantum dot with a 1-dodecanthiol ligand and its application to a quantum dot light-emitting diode. The ligand change from oleylamine to 1-dodecanthiol, which were connected around the InP/ZnS quantum dot, was confirmed by Fourier-transform infrared spectroscopy and thermal analysis. The absorption peak was blue-shifted by changing 1-dodecanthiol ligands from oleylamine ligands to prevent the unexpected nucleation of the InP core. In addition, the luminance of the light-emitting device was improved by using the InP/ZnS quantum dot with 1-dodecanthiol ligands, and the maximum current efficiency of 7.2 × 10-3 cd/A was achieved. The 1-dodecanthiol ligand is often used for capping to reduce the number of surface defects and/or prevent unexpected core growth, resulting in reduced Auger recombination. This result indicates that 1-dodecanthiol ligands prevent the deactivation of excitons while injecting carriers by applying a voltage, resulting in a high luminance efficiency.

Spectrophotometric method for determination of bifunctional macrocyclic ligands in macrocyclic ligand-protein conjugates

International Nuclear Information System (INIS)

Dadachova, E.; Chappell, L.L.; Brechbiel, M.W.

1999-01-01

A simple spectrophotometric assay for determination of bifunctional polyazacarboxylate-macrocyclic ligands of different sizes that are conjugated to proteins has been developed for: 12-membered macrocycle DOTA (2-[4-nitrobenzyl]-1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) and analogs, the 15-membered PEPA macrocycle (2-[4-nitrobenzyl]-1,4,7,10,13-pentaazacyclopentadecane-N,N',N'',N''',N'''' -pentaacetic acid), and the large 18-membered macrocycle HEHA (1,4,7,10,13,16-hexaazacyclooctadecane-N,N',N'',N''',N''''-hexaacetic acid). The method is based on titration of the blue-colored 1:1 Pb(II)-Arsenazo III (AAIII) complex with the polyazacarboxylate macrocyclic ligand in the concentration range of 0-2.5 μM, wherein color change occurring upon transchelation of the Pb(II) from the AAIII to the polyazamacrocyclic ligand is monitored at 656 nm. The assay is performed at ambient temperature within 20 min without any interfering interaction between the protein and Pb(II)-AA(III) complex. Thus, this method also provides a ligand-to-protein ratio (L/P ratio) that reflects the effective number of ligands per protein molecule available to radiolabeling. The method is not suitable for 14-membered TETA macrocycle (2-[4-nitrobenzyl]-1, 4, 8, 11-tetraazacyclotetradecane N,N',N'',N'''-tetraacetic acid) because of low stability constant of Pb(II)-TETA complex. The method is rapid, simple and may be customized for other polyazacarboxylate macrocyclic ligands

Rosetta Ligand docking with flexible XML protocols.

Science.gov (United States)

Lemmon, Gordon; Meiler, Jens

2012-01-01

RosettaLigand is premiere software for predicting how a protein and a small molecule interact. Benchmark studies demonstrate that 70% of the top scoring RosettaLigand predicted interfaces are within 2Å RMSD from the crystal structure [1]. The latest release of Rosetta ligand software includes many new features, such as (1) docking of multiple ligands simultaneously, (2) representing ligands as fragments for greater flexibility, (3) redesign of the interface during docking, and (4) an XML script based interface that gives the user full control of the ligand docking protocol.

Tungsten(VI) Carbyne/Bis(carbene) Tautomerization Enabled by N-Donor SBA15 Surface Ligands: A Solid-State NMR and DFT Study

KAUST Repository

Bendjeriou-Sedjerari, Anissa

2016-08-11

Designing supported well-defined bis(carbene) complexes remains a key challenge in heterogeneous catalysis. The reaction of W(CtBu)(CH(2)tBu)(3) with amine-modified mesoporous SBA15 silica, which has vicinal silanol/silylamine pairs [(SiOH)(SiNH2)], leads to [(SiNH2-)(SiO-)W(CHtBu)(CH(2)tBu)(2)] and [(SiNH2-)(SiO-)W(=CHtBu)(2)(CH(2)tBu). Variable temperature, H-1-H-1 2D double-quantum, H-1-C-13 HETCOR, and HETCOR with spin diffusion solid-state NMR spectroscopy demonstrate tautomerization between the alkyl alkylidyne and the bis(alkylidene) on the SBA15 surface. Such equilibrium is possible through the coordination of W to the surface [(Si-OH)(Si-NH2)] groups, which act as a [N,O] pincer ligand. DFT calculations provide a rationalization for the surface-complex tautomerization and support the experimental results. This direct observation of such a process shows the strong similarity between molecular mechanisms in homogeneous and heterogeneous catalysis. In propane metathesis (at 150 degrees C), the tungsten bis(carbene) tautomer is favorable, with a turnover number (TON) of 262. It is the highest TON among all the tungsten alkyl-supported catalysts.

Tungsten(VI) Carbyne/Bis(carbene) Tautomerization Enabled by N-Donor SBA15 Surface Ligands: A Solid-State NMR and DFT Study

KAUST Repository

Bendjeriou-Sedjerari, Anissa; Sofack-Kreutzer, Julien; Minenkov, Yury; Abou-Hamad, Edy; Hamzaoui, Bilel; Werghi, Baraa; Anjum, Dalaver H.; Cavallo, Luigi; Huang, Kuo-Wei; Basset, Jean-Marie

2016-01-01

Designing supported well-defined bis(carbene) complexes remains a key challenge in heterogeneous catalysis. The reaction of W(CtBu)(CH(2)tBu)(3) with amine-modified mesoporous SBA15 silica, which has vicinal silanol/silylamine pairs [(SiOH)(SiNH2)], leads to [(SiNH2-)(SiO-)W(CHtBu)(CH(2)tBu)(2)] and [(SiNH2-)(SiO-)W(=CHtBu)(2)(CH(2)tBu). Variable temperature, H-1-H-1 2D double-quantum, H-1-C-13 HETCOR, and HETCOR with spin diffusion solid-state NMR spectroscopy demonstrate tautomerization between the alkyl alkylidyne and the bis(alkylidene) on the SBA15 surface. Such equilibrium is possible through the coordination of W to the surface [(Si-OH)(Si-NH2)] groups, which act as a [N,O] pincer ligand. DFT calculations provide a rationalization for the surface-complex tautomerization and support the experimental results. This direct observation of such a process shows the strong similarity between molecular mechanisms in homogeneous and heterogeneous catalysis. In propane metathesis (at 150 degrees C), the tungsten bis(carbene) tautomer is favorable, with a turnover number (TON) of 262. It is the highest TON among all the tungsten alkyl-supported catalysts.

Ligand-receptor Interactions by NMR Spectroscopy

Directory of Open Access Journals (Sweden)

Novak. P.

2008-04-01

Full Text Available Today NMR spectroscopy is a method of choice for elucidation of interactions between biomolecules and the potential ligands. Knowledge on these interactions is an essential prerequisite for the rational drug design. The most important contribution of NMR to drug design a few years ago was the 3D structure determination of proteins. Besides delivering the 3D structures of the free proteins as a raw material for the modeling studies on ligand binding, NMR can directly yield valuable experimental data on the biologically important protein-ligand complexes. In addition to X-ray diffraction, NMR spectroscopy can provide information on the internal protein dynamics ordynamics of intermolecular interactions. Changes in NMR parameters allow us to detect ("SAR by NMR" and quantitatively determine binding affinities (titration, diffusion NMR experiments, etc. of potential ligands. Also, it is possible to determine the binding site and conformations of ligands, receptors and receptor-ligand complexes with the help of NMR methods such as tr-NOESY. Epitopes or functional groups responsible for binding of ligands to the receptor can be identified by employing STD or WaterLOGSY experiments. In this review are described some of the most frequent NMR methods for the characterization of the interactions between biomolecules and ligands, together with their advantages and disadvantages.

Endocytosis via galactose receptors in vivo. Ligand size directs uptake by hepatocytes and/or liver macrophages

International Nuclear Information System (INIS)

Schlepper-Schaefer, J.; Huelsmann, D.; Djovkar, A.; Meyer, H.E.; Herbertz, L.; Kolb, H.; Kolb-Bachofen, V.

1986-01-01

The intrahepatic binding and uptake of variously sized ligands with terminal galactosyl residues is rat liver was followed. The ligands were administered to prefixed livers in binding studies and in vivo and in situ (serum-free perfused livers) in uptake studies. Gold sols with different particle diameters were prepared: 5 nm (Au 5 ), 17 nm (Au 17 ), 50 nm (Au 50 ) and coated with galactose exposing glycoproteins (asialofetuin (ASF) or lactosylated BSA (LacBSA)). Electron microscopy of mildly prefixed livers perfused with LacBSA-Au 5 in serum-free medium showed ligand binding to liver macrophages, hepatocytes and endothelial cells. Ligands bound to prefixed cell surfaces reflect the initial distribution of receptor activity: pre-aggregated clusters of ligands are found on liver macrophages, single particles statistically distributed on hepatocytes and pre-aggregated clusters of particles restricted to coated pits on endothelial cells. Ligand binding is prevented in the presence of 80 mM N-acetylgalactosamine (GalNAc), while N-acetylglucosamine (GlcNAc) is without effect. Electron microscopy of livers after ligand injection into the tail vein shows that in vivo uptake of electron-dense galactose particles by liver cells is size-dependent. In vivo uptake by liver macrophages is mediated by galactose-specific recognition as shown by inhibition with GalNAc

A Ferrocene-Based Catecholamide Ligand: the Consequences of Ligand Swivel for Directed Supramolecular Self-Assembly

Energy Technology Data Exchange (ETDEWEB)

Mugridge, Jeffrey; Fiedler, Dorothea; Raymond, Kenneth

2010-02-04

A ferrocene-based biscatecholamide ligand was prepared and investigated for the formation of metal-ligand supramolecular assemblies with different metals. Reaction with Ge(IV) resulted in the formation of a variety of Ge{sub n}L{sub m} coordination complexes, including [Ge{sub 2}L{sub 3}]{sup 4-} and [Ge{sub 2}L{sub 2}({mu}-OMe){sub 2}]{sup 2-}. The ligand's ability to swivel about the ferrocenyl linker and adopt different conformations accounts for formation of many different Ge{sub n}L{sub m} species. This study demonstrates why conformational ligand rigidity is essential in the rational design and directed self-assembly of supramolecular complexes.

Extracellular Polymeric Substances Govern the Surface Charge of Biogenic Elemental Selenium Nanoparticles

KAUST Repository

Jain, Rohan

2015-02-03

© 2014 American Chemical Society. The origin of the organic layer covering colloidal biogenic elemental selenium nanoparticles (BioSeNPs) is not known, particularly in the case when they are synthesized by complex microbial communities. This study investigated the presence of extracellular polymeric substances (EPS) on BioSeNPs. The role of EPS in capping the extracellularly available BioSeNPs was also examined. Fourier transform infrared (FT-IR) spectroscopy and colorimetric measurements confirmed the presence of functional groups characteristic of proteins and carbohydrates on the BioSeNPs, suggesting the presence of EPS. Chemical synthesis of elemental selenium nanoparticles in the presence of EPS, extracted from selenite fed anaerobic granular sludge, yielded stable colloidal spherical selenium nanoparticles. Furthermore, extracted EPS, BioSeNPs, and chemically synthesized EPS-capped selenium nanoparticles had similar surface properties, as shown by ζ-potential versus pH profiles and isoelectric point measurements. This study shows that the EPS of anaerobic granular sludge form the organic layer present on the BioSeNPs synthesized by these granules. The EPS also govern the surface charge of these BioSeNPs, thereby contributing to their colloidal properties, hence affecting their fate in the environment and the efficiency of bioremediation technologies.

Vesicular Stomatitis Virus Infection Promotes Immune Evasion by Preventing NKG2D-Ligand Surface Expression

DEFF Research Database (Denmark)

Jensen, Helle; Andresen, Lars; Nielsen, Jens

2011-01-01

Vesicular stomatitis virus (VSV) has recently gained attention for its oncolytic ability in cancer treatment. Initially, we hypothesized that VSV infection could increase immune recognition of cancer cells through induction of the immune stimulatory NKG2D-ligands. Here we show that VSV infection ...

Surface treatment of nanocrystal quantum dots after film deposition

Science.gov (United States)

Sykora, Milan; Koposov, Alexey; Fuke, Nobuhiro

2015-02-03

Provided are methods of surface treatment of nanocrystal quantum dots after film deposition so as to exchange the native ligands of the quantum dots for exchange ligands that result in improvement in charge extraction from the nanocrystals.

Macrocyclic G-quadruplex ligands

DEFF Research Database (Denmark)

Nielsen, M C; Ulven, Trond

2010-01-01

are macrocyclic structures which have been modeled after the natural product telomestatin or from porphyrin-based ligands discovered in the late 1990s. These two structural classes of G-quadruplex ligands are reviewed here with special attention to selectivity and structure-activity relationships, and with focus...

Heterobifunctional crosslinkers for tethering single ligand molecules to scanning probes

International Nuclear Information System (INIS)

Riener, Christian K.; Kienberger, Ferry; Hahn, Christoph D.; Buchinger, Gerhard M.; Egwim, Innocent O.C.; Haselgruebler, Thomas; Ebner, Andreas; Romanin, Christoph; Klampfl, Christian; Lackner, Bernd; Prinz, Heino; Blaas, Dieter; Hinterdorfer, Peter; Gruber, Hermann J.

2003-01-01

Single molecule recognition force microscopy (SMRFM) is a versatile atomic force microscopy (AFM) method to probe specific interactions of cognitive molecules on the single molecule level. It allows insights to be gained into interaction potentials and kinetic barriers and is capable of mapping interaction sites with nm positional accuracy. These applications require a ligand to be attached to the AFM tip, preferably by a distensible poly(ethylene glycol) (PEG) chain between the measuring tip and the ligand molecule. The PEG chain greatly facilitates specific binding of the ligand to immobile receptor sites on the sample surface. The present study contributes to tip-PEG-ligand tethering in three ways: (i) a convenient synthetic route was found to prepare NH 2 -PEG-COOH which is the key intermediate for long heterobifunctional crosslinkers; (ii) a variety of heterobifunctional PEG derivatives for tip-PEG-ligand linking were prepared from NH 2 -PEG-COOH; (iii) in particular, a new PEG crosslinker with one thiol-reactive end and one terminal nitrilotriacetic acid (NTA) group was synthesized and successfully used to tether His 6 -tagged protein molecules to AFM tips via noncovalent NTA-Ni 2+ -His 6 bridges. The new crosslinker was applied to link a recombinant His 6 -tagged fragment of the very-low density lipoprotein receptor to the AFM tip whereupon specific docking to the capsid of human rhinovirus particles was observed by force microscopy. In a parallel study, the specific interaction of the small GTPase Ran with the nuclear import receptor importin β1 was studied in detail by SMRFM, using the new crosslinker to link His 6 -tagged Ran to the measuring tip [Nat. Struct. Biol. (2003), 10, 553-557

Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

International Nuclear Information System (INIS)

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei

2015-01-01

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H_2ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H_2hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd_2(2,6-ndc)_2(bpp)(DMF)]·2DMF (1) and [Cd_3(hmdb)_3(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.

Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

Energy Technology Data Exchange (ETDEWEB)

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei, E-mail: hanlei@nbu.edu.cn

2015-12-15

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H{sub 2}ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H{sub 2}hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd{sub 2}(2,6-ndc){sub 2}(bpp)(DMF)]·2DMF (1) and [Cd{sub 3}(hmdb){sub 3}(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.

The connection between metal ion affinity and ligand affinity in integrin I domains

DEFF Research Database (Denmark)

Vorup-Jensen, Thomas; Waldron, TT; Astrof, N

2007-01-01

Integrins are cell-surface heterodimeric proteins that mediate cell-cell, cell-matrix, and cell-pathogen interactions. Half of the known integrin alpha subunits contain inserted domains (I domains) that coordinate ligand through a metal ion. Although the importance of conformational changes withi...

A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

Science.gov (United States)

Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

2014-01-01

Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

Structural properties of MHC class II ligands, implications for the prediction of MHC class II epitopes.

Directory of Open Access Journals (Sweden)

Kasper Winther Jørgensen

2010-12-01

Full Text Available Major Histocompatibility class II (MHC-II molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Prediction of MHC class II ligands is complicated by the open binding cleft of the MHC class II molecule, allowing binding of peptides extending out of the binding groove. Furthermore, only a few HLA-DR alleles have been characterized with a sufficient number of peptides (100-200 peptides per allele to derive accurate description of their binding motif. Little work has been performed characterizing structural properties of MHC class II ligands. Here, we perform one such large-scale analysis. A large set of SYFPEITHI MHC class II ligands covering more than 20 different HLA-DR molecules was analyzed in terms of their secondary structure and surface exposure characteristics in the context of the native structure of the corresponding source protein. We demonstrated that MHC class II ligands are significantly more exposed and have significantly more coil content than other peptides in the same protein with similar predicted binding affinity. We next exploited this observation to derive an improved prediction method for MHC class II ligands by integrating prediction of MHC- peptide binding with prediction of surface exposure and protein secondary structure. This combined prediction method was shown to significantly outperform the state-of-the-art MHC class II peptide binding prediction method when used to identify MHC class II ligands. We also tried to integrate N- and O-glycosylation in our prediction methods but this additional information was found not to improve prediction performance. In summary, these findings strongly suggest that local structural properties influence antigen processing and/or the accessibility of peptides to the MHC class II molecule.

Secondary ligand-directed assembly of Co(II) coordination polymers based on a pyridine carboxylate ligand

International Nuclear Information System (INIS)

Cao, Ke-Li; Zhang, Yi-Ping; Cai, Yi-Ni; Xu, Xiao-Wei; Feng, Yun-Long

2014-01-01

To investigate the influence of hydrogen bonds and secondary ligands on the structures and properties of the resulting frameworks, five new Co(II) compounds have been synthesized by the reactions of Co(II) salts and 3,5-bis(pyridin-4-ylmethoxy)benzoic acid (HL) with four rationally selected dicarboxylic acid ligands. Without secondary ligand, we got one compound [CoL 2 (H 2 O) 2 ] n ·2nH 2 O (1), which possesses a 1D chain structure. In the presence of ancillary ligands, namely, 1,3-adamantanedicarboxylic acid (H 2 adbc), terephthalic acid (H 2 tpa), thiophene-2,5-dicarboxylic acid (H 2 tdc) and 1,4-benzenedithioacetic acid (H 2 bdtc), four 3D structures [Co 2 L 2 (adbc)] n ·nH 2 O (2), [Co 2 L 2 (tpa)] n (3), [Co 2 L 2 (tdc)] n (4), [Co 2 L 2 (bdtc)(H 2 O)] n (5) were obtained, respectively. It can be observed from the architectures of 1–5 that hydrogen bonds and secondary ligands both have great effects on the spatial connective fashions, resulting in the formation of various dimensional compounds. The XRPD, TGA data of title polymers and the magnetic properties for 2 and 5 have also been investigated. - Graphical abstract: The structural differences show that the ancillary ligands have great effects on the spatial connective fashions, resulting in the formation of various dimensional compounds. - Highlights: • Five new Co(II) coordination polymers have been synthesized by solvothermal reactions based on 3,5-bis(pyridin-4-ylmethoxy)benzoic acid (HL). • The long-flexible ligand (HL) is a good candidate to produce interpenetrating architectures. • The secondary dicarboxylic acid ligands play important roles in the spatial connective fashions and the formation of various dimensional compounds. • The magnetism studies show that both 2 and 5 exhibit antiferromagnetic interactions

Room-Temperature Triple-Ligand Surface Engineering Synergistically Boosts Ink Stability, Recombination Dynamics, and Charge Injection toward EQE-11.6% Perovskite QLEDs.

Science.gov (United States)

Song, Jizhong; Li, Jinhang; Xu, Leimeng; Li, Jianhai; Zhang, Fengjuan; Han, Boning; Shan, Qingsong; Zeng, Haibo

2018-06-10

Developing low-cost and high-quality quantum dots (QDs) or nanocrystals (NCs) and their corresponding efficient light-emitting diodes (LEDs) is crucial for the next-generation ultra-high-definition flexible displays. Here, there is a report on a room-temperature triple-ligand surface engineering strategy to play the synergistic role of short ligands of tetraoctylammonium bromide (TOAB), didodecyldimethylammonium bromide (DDAB), and octanoic acid (OTAc) toward "ideal" perovskite QDs with a high photoluminescence quantum yield (PLQY) of >90%, unity radiative decay in its intrinsic channel, stable ink characteristics, and effective charge injection and transportation in QD films, resulting in the highly efficient QD-based LEDs (QLEDs). Furthermore, the QD films with less nonradiative recombination centers exhibit improved PL properties with a PLQY of 61% through dopant engineering in A-site. The robustness of such properties is demonstrated by the fabrication of green electroluminescent LEDs based on CsPbBr 3 QDs with the peak external quantum efficiency (EQE) of 11.6%, and the corresponding peak internal quantum efficiency (IQE) and power efficiency are 52.2% and 44.65 lm W -1 , respectively, which are the most-efficient perovskite QLEDs with colloidal CsPbBr 3 QDs as emitters up to now. These results demonstrate that the as-obtained QD inks have a wide range application in future high-definition QD displays and high-quality lightings. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Specific ability of sulfur-ligands on removal of 203Hg-labeled organomercury from hemoglobin in comparison with nitrogen-ligands

International Nuclear Information System (INIS)

Hojo, Yasuji; Sugiura, Yukio; Tanaka, Hisashi

1975-01-01

Removal of 203 Hg-labeled organomercurials, bound to sulfhydryl groups of hemoglobin, by various chelating agents was investigated by the use of equilibrium dialysis. Organomercurials employed were chlormerodrin, methylmercury, ethylmercury and phenylmercury compounds. Higher and more specific effects of the sulfur-ligands, such as penicillamine and glutathione, on removal of organomercurial were found as compared with those of the nitrogen-ligands such as EDTA, glycine and polymethylenediamines. Linear correlation was observed between the degree of organomercury elimination from hemoglobin and the stability constant (log K 1 ) of 1:1 organomercury complex in both the sulfur- and nitrogen-ligand systems and at the same value of log K 1 , the elimination-effect of sulfur-ligands was extremely greater than that of the nitrogen-ligands. The relationship between the average percentage of removal and the Taft's polar substituent constant of organic moiety of the metal was also linear among the organomercury compounds other than chlormerodrin. The average removal percentage by sulfur-ligands increased in the order, ethylmercury>methylmercury>phenylmercury, while that of the nitrogen-ligands was not different among the organomercurials investigated. In addition, direct ligand-exchange reaction between hemoglobin-SH and the ligand coordinating-atom (S or N) against organomercurials rather than Ssub(N2) reaction via the ternary complex, hemoglobin-S-RHg-ligand, is postulated. (auth.)

Ligand cluster-based protein network and ePlatton, a multi-target ligand finder.

Science.gov (United States)

Du, Yu; Shi, Tieliu

2016-01-01

Small molecules are information carriers that make cells aware of external changes and couple internal metabolic and signalling pathway systems with each other. In some specific physiological status, natural or artificial molecules are used to interact with selective biological targets to activate or inhibit their functions to achieve expected biological and physiological output. Millions of years of evolution have optimized biological processes and pathways and now the endocrine and immune system cannot work properly without some key small molecules. In the past thousands of years, the human race has managed to find many medicines against diseases by trail-and-error experience. In the recent decades, with the deepening understanding of life and the progress of molecular biology, researchers spare no effort to design molecules targeting one or two key enzymes and receptors related to corresponding diseases. But recent studies in pharmacogenomics have shown that polypharmacology may be necessary for the effects of drugs, which challenge the paradigm, 'one drug, one target, one disease'. Nowadays, cheminformatics and structural biology can help us reasonably take advantage of the polypharmacology to design next-generation promiscuous drugs and drug combination therapies. 234,591 protein-ligand interactions were extracted from ChEMBL. By the 2D structure similarity, 13,769 ligand emerged from 156,151 distinct ligands which were recognized by 1477 proteins. Ligand cluster- and sequence-based protein networks (LCBN, SBN) were constructed, compared and analysed. For assisting compound designing, exploring polypharmacology and finding possible drug combination, we integrated the pathway, disease, drug adverse reaction and the relationship of targets and ligand clusters into the web platform, ePlatton, which is available at http://www.megabionet.org/eplatton. Although there were some disagreements between the LCBN and SBN, communities in both networks were largely the same

Self-assembling triblock proteins for biofunctional surface modification

Science.gov (United States)

Fischer, Stephen E.

Despite the tremendous promise of cell/tissue engineering, significant challenges remain in engineering functional scaffolds to precisely regulate the complex processes of tissue growth and development. As the point of contact between the cells and the scaffold, the scaffold surface plays a major role in mediating cellular behaviors. In this dissertation, the development and utility of self-assembling, artificial protein hydrogels as biofunctional surface modifiers is described. The design of these recombinant proteins is based on a telechelic triblock motif, in which a disordered polyelectrolyte central domain containing embedded bioactive ligands is flanked by two leucine zipper domains. Under moderate conditions of temperature and pH, the leucine zipper end domains form amphiphilic alpha-helices that reversibly associate into homo-trimeric aggregates, driving hydrogel formation. Moreover, the amphiphilic nature of these helical domains enables surface adsorption to a variety of scaffold materials to form biofunctional protein coatings. The nature and stability of these coatings in various solution conditions, and their interaction with mammalian cells is the primary focus of this dissertation. In particular, triblock protein coatings functionalized with cell recognition sequences are shown to produce well-defined surfaces with precise control over ligand density. The impact of this is demonstrated in multiple cell types through ligand density-dependent cell-substrate interactions. To improve the stability of these physically self-assembled coatings, two covalent crosslinking strategies are described---one in which a zero-length chemical crosslinker (EDC) is utilized and a second in which disulfide bonds are engineered into the recombinant proteins. These targeted crosslinking approaches are shown to increase the stability of surface adsorbed protein layers with minimal effect on the presentation of many bioactive ligands. Finally, to demonstrate the versatility

Studies on ligand exchange reaction of functionalized mercaptothiadiazole compounds onto citrate capped gold nanoparticles

International Nuclear Information System (INIS)

Kalimuthu, Palraj; John, S. Abraham

2010-01-01

Mercaptothiadiazole ligands functionalized with thiol (2,5-dimercapto-1,3,4-thiadiazole (DMT)) and methyl (5-methyl-2-mercapto-1,3,4-thiadiazole (MMT)) groups capped onto citrate capped gold nanoparticles (C-AuNPs) by ligand exchange reaction was investigated by UV-vis spectroscopy, FT-IR spectroscopy and transmission electron microscopy (TEM) techniques. The surface plasmon resonance band at 522 nm for C-AuNPs was shifted to 530 nm after capping with DMT whereas an additional band was observed at 630 nm due to aggregation in addition to a shift in the band at 522 nm after capping of MMT onto C-AuNPs. Thus, capping of DMT onto C-AuNPs leads to the formation of stable AuNPs while capping of MMT leads to the formation of unstable AuNPs. FT-IR studies show that the citrate ions were completely replaced by both DMT and MMT ligands from the AuNPs. TEM images indicate that the size and shape of the AuNPs remain same after capping of these ligands.

Immobilisation of ligands by radio-derivatized polymers; Immobilisering av ligander med radioderiverte polymerer

Energy Technology Data Exchange (ETDEWEB)

Varga, J.M.; Fritsch, P.

1995-01-30

The invention relates to radio-derivatized polymers and a method of producing them by contacting non-polymerizable conjugands with radiolysable polymers in the presence of irradiation. The resulting radio-derivatized polymers can be further linked with ligand of organic or inorganic nature to immobilize such ligands. 2 figs., 5 tabs.

Functionalization of Block Copolymer Vesicle Surfaces

Directory of Open Access Journals (Sweden)

Wolfgang Meier

2011-01-01

Full Text Available In dilute aqueous solutions certain amphiphilic block copolymers self-assemble into vesicles that enclose a small pool of water with a membrane. Such polymersomes have promising applications ranging from targeted drug-delivery devices, to biosensors, and nanoreactors. Interactions between block copolymer membranes and their surroundings are important factors that determine their potential biomedical applications. Such interactions are influenced predominantly by the membrane surface. We review methods to functionalize block copolymer vesicle surfaces by chemical means with ligands such as antibodies, adhesion moieties, enzymes, carbohydrates and fluorophores. Furthermore, surface-functionalization can be achieved by self-assembly of polymers that carry ligands at their chain ends or in their hydrophilic blocks. While this review focuses on the strategies to functionalize vesicle surfaces, the applications realized by, and envisioned for, such functional polymersomes are also highlighted.

Ligand-accelerated non-directed C-H functionalization of arenes

Science.gov (United States)

Wang, Peng; Verma, Pritha; Xia, Guoqin; Shi, Jun; Qiao, Jennifer X.; Tao, Shiwei; Cheng, Peter T. W.; Poss, Michael A.; Farmer, Marcus E.; Yeung, Kap-Sun; Yu, Jin-Quan

2017-11-01

The directed activation of carbon-hydrogen bonds (C-H) is important in the development of synthetically useful reactions, owing to the proximity-induced reactivity and selectivity that is enabled by coordinating functional groups. Palladium-catalysed non-directed C-H activation could potentially enable further useful reactions, because it can reach more distant sites and be applied to substrates that do not contain appropriate directing groups; however, its development has faced substantial challenges associated with the lack of sufficiently active palladium catalysts. Currently used palladium catalysts are reactive only with electron-rich arenes, unless an excess of arene is used, which limits synthetic applications. Here we report a 2-pyridone ligand that binds to palladium and accelerates non-directed C-H functionalization with arene as the limiting reagent. This protocol is compatible with a broad range of aromatic substrates and we demonstrate direct functionalization of advanced synthetic intermediates, drug molecules and natural products that cannot be used in excessive quantities. We also developed C-H olefination and carboxylation protocols, demonstrating the applicability of our methodology to other transformations. The site selectivity in these transformations is governed by a combination of steric and electronic effects, with the pyridone ligand enhancing the influence of sterics on the selectivity, thus providing complementary selectivity to directed C-H functionalization.

Reactivity of halide and pseudohalide ligands

International Nuclear Information System (INIS)

Kukushkin, Yu.N.

1987-01-01

Reactivity of halide and pseudohalide (cyanide, azide, thiocyanate, cyanate) ligands tending to form bridge bonds in transition metal (Re, Mo, W) complexes is considered. Complexes where transition metal salts are ligands of other, complex-forming ion, are described. Transformation of innerspheric pseudohalide ligands is an important way of directed synthesis of these metal coordination compounds

Screening Effect of PEG on Avidin Binding to Liposome Surface Receptors

DEFF Research Database (Denmark)

Kaasgaard, Thomas; Mouritsen, Ole G.; Jørgensen, Kent

2000-01-01

This study investigates the screening effect of poly(ethylene glycol)-phospholipids (PE-PEG) on the interaction of avidin with PEGylated liposomes containing surface-bound biotin ligands. The influence of grafting density and lipopolymer chain length is examined. A simple fluorescence assay....... Furthermore. it is found that none of the lipopolymers completely prevents avidin from reaching the surface-bound biotin ligands....

Controlled adsorption of cytochrome c to nanostructured gold surfaces

International Nuclear Information System (INIS)

Gomes, Inês; Feio, Maria J.; Santos, Nuno C.; Eaton, Peter; Serro, Ana Paula; Saramago, Benilde; Pereira, Eulália; Franco, Ricardo

2012-01-01

Controlled electrostatic physisorption of horse heart cytochrome c (Cyt c) onto nanostructured gold surfaces was investigated using Quartz-Crystal Microbalance measurements in planar gold surfaces with or without functionalization using a self-assembled monolayer (SAM) of the alkanethiol mercaptoundecanoic acid (MUA). MUA is a useful functionalization ligand for gold surfaces, shedding adsorbed biomolecules from the excessive electron density of the metal. A parallel analysis was conducted in the corresponding curved surfaces of 15 nm gold nanoparticles (AuNPs), using zeta-potential and UV– visible spectroscopy. Atomic Force Microscopy of both types of functionalized gold surfaces with a MUA SAM, allowed for visualization of Cyt c deposits on the nanostructured gold surface. The amount of Cyt c adsorbed onto the gold surface could be controlled by the solution pH. For the assays conducted at pH 4.5, when MUA SAM- functionalized planar gold surfaces are positive or neutral, and Cyt c has a positive net charge, only 13 % of the planar gold surface area was coated with protein. In contrast, at pH 7.4, when MUA SAM-functionalized planar gold surfaces and Cyt c have opposite charges, a protein coverage of 28 % could be observed implying an adsorption process strongly governed by electrostatic forces. Cyt c adsorption on planar and curved gold surfaces are found to be greatly favored by the presence of a MUA-capping layer. In particular, on the AuNPs, the binding constant is three times larger than the binding constant obtained for the original citrate-capped AuNPs.

Controlled adsorption of cytochrome c to nanostructured gold surfaces

Energy Technology Data Exchange (ETDEWEB)

Gomes, Ines [Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, REQUIMTE, Departamento de Quimica (Portugal); Feio, Maria J. [Faculdade de Ciencias da Universidade do Porto, REQUIMTE, Departamento de Quimica e Bioquimica (Portugal); Santos, Nuno C. [Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular (Portugal); Eaton, Peter [Faculdade de Ciencias da Universidade do Porto, REQUIMTE, Departamento de Quimica e Bioquimica (Portugal); Serro, Ana Paula; Saramago, Benilde [Centro de Quimica Estrutural, Instituto Superior Tecnico (Portugal); Pereira, Eulalia [Faculdade de Ciencias da Universidade do Porto, REQUIMTE, Departamento de Quimica e Bioquimica (Portugal); Franco, Ricardo, E-mail: ricardo.franco@fct.unl.pt [Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, REQUIMTE, Departamento de Quimica (Portugal)

2012-12-15

Controlled electrostatic physisorption of horse heart cytochrome c (Cyt c) onto nanostructured gold surfaces was investigated using Quartz-Crystal Microbalance measurements in planar gold surfaces with or without functionalization using a self-assembled monolayer (SAM) of the alkanethiol mercaptoundecanoic acid (MUA). MUA is a useful functionalization ligand for gold surfaces, shedding adsorbed biomolecules from the excessive electron density of the metal. A parallel analysis was conducted in the corresponding curved surfaces of 15 nm gold nanoparticles (AuNPs), using zeta-potential and UV- visible spectroscopy. Atomic Force Microscopy of both types of functionalized gold surfaces with a MUA SAM, allowed for visualization of Cyt c deposits on the nanostructured gold surface. The amount of Cyt c adsorbed onto the gold surface could be controlled by the solution pH. For the assays conducted at pH 4.5, when MUA SAM- functionalized planar gold surfaces are positive or neutral, and Cyt c has a positive net charge, only 13 % of the planar gold surface area was coated with protein. In contrast, at pH 7.4, when MUA SAM-functionalized planar gold surfaces and Cyt c have opposite charges, a protein coverage of 28 % could be observed implying an adsorption process strongly governed by electrostatic forces. Cyt c adsorption on planar and curved gold surfaces are found to be greatly favored by the presence of a MUA-capping layer. In particular, on the AuNPs, the binding constant is three times larger than the binding constant obtained for the original citrate-capped AuNPs.

Metal-ligand cooperative activation of nitriles by a ruthenium complex with a de-aromatized PNN pincer ligand

NARCIS (Netherlands)

Eijsink, Linda E; Perdriau, Sébastien C P; de Vries, Johannes G; Otten, Edwin

2016-01-01

The pincer complex (PNN)RuH(CO), with a de-aromatized pyridine in the ligand backbone, is shown to react with nitriles in a metal-ligand cooperative manner. This leads to the formation of a series of complexes with new Ru-N(nitrile) and C(ligand)-C(nitrile) bonds. The initial nitrile cycloaddition

Study of the role of the ligands coordinated at the surface of pure Wuestite nanoparticles prepared following a room temperature organometallic method: Evidence of ferromagnetic - in shell- and antiferromagnetic - in core magnetic behaviors

Energy Technology Data Exchange (ETDEWEB)

Glaria, Arnaud [CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse (France); Universite de Toulouse, UPS, INPT, LCC, F-31077 Toulouse (France); Kahn, Myrtil L., E-mail: myrtil.kahn@lcc-toulouse.fr [CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse (France); Universite de Toulouse, UPS, INPT, LCC, F-31077 Toulouse (France); Chaudret, Bruno [CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse (France); Universite de Toulouse, UPS, INPT, LCC, F-31077 Toulouse (France); Lecante, Pierre; Casanove, Marie-Jose [CNRS, CEMES (Centre d' Elaboration des Materiaux et d' Etudes Structurales), 29 rue Jeanne Marvig, BP 4347, 31055 Toulouse Cedex (France); Barbara, Bernard, E-mail: bernard.barbara@grenoble.cnrs.fr [Institut Louis Neel, CNRS, 25 Av. des martyrs, BP 166, 38042 Grenoble Cedex 09 (France)

2011-09-15

Highlights: {yields} Pure Wuestite (Fe{sub 1-y}O) nanoparticles synthesized by organometallic chemistry. {yields} The influence of the surface ligands on the magnetic properties. {yields} Ferromagnetic core-antiferromagnetic shell magnetic nanoparticles. - Abstract: Wuestite particles (Fe{sub 1-y}O) are synthesized using controlled hydrolysis at room temperature of [Fe(N(SiMe{sub 3}){sub 2}){sub 2}] and stabilized by amine ligands. This method leads to 5 nm pure wuestite particles. This phase is clearly identified by transmission electron microscopy and wide angle X-ray scattering. Distortion in the crystallographic structure has been demonstrated. Particular attention is paid on the Fe(III) formation. Moreover, a combination of Moessbauer spectroscopy and SQuID measurements, revealed that the particles are composed of an antiferromagnetic core surrounded by a ferromagnetic shell. According to the Neel theory, the Fe(III) and Fe(II) ions present in the particles are ferromagnetically coupled and the proportion of Fe(III) ions varies from 3.9 to 7.1% as a function of the amine ligand.

A high pressure study of calmodulin-ligand interactions using small-angle X-ray and elastic incoherent neutron scattering.

Science.gov (United States)

Cinar, Süleyman; Al-Ayoubi, Samy; Sternemann, Christian; Peters, Judith; Winter, Roland; Czeslik, Claus

2018-01-31

Calmodulin (CaM) is a Ca 2+ sensor and mediates Ca 2+ signaling through binding of numerous target ligands. The binding of ligands by Ca 2+ -saturated CaM (holo-CaM) is governed by attractive hydrophobic and electrostatic interactions that are weakened under high pressure in aqueous solutions. Moreover, the potential formation of void volumes upon ligand binding creates a further source of pressure sensitivity. Hence, high pressure is a suitable thermodynamic variable to probe protein-ligand interactions. In this study, we compare the binding of two different ligands to holo-CaM as a function of pressure by using X-ray and neutron scattering techniques. The two ligands are the farnesylated hypervariable region (HVR) of the K-Ras4B protein, which is a natural binding partner of holo-CaM, and the antagonist trifluoperazine (TFP), which is known to inhibit holo-CaM activity. From small-angle X-ray scattering experiments performed up to 3000 bar, we observe a pressure-induced partial unfolding of the free holo-CaM in the absence of ligands, where the two lobes of the dumbbell-shaped protein are slightly swelled. In contrast, upon binding TFP, holo-CaM forms a closed globular conformation, which is pressure stable at least up to 3000 bar. The HVR of K-Ras4B shows a different binding behavior, and the data suggest the dissociation of the holo-CaM/HVR complex under high pressure, probably due to a less dense protein contact of the HVR as compared to TFP. The elastic incoherent neutron scattering experiments corroborate these findings. Below 2000 bar, pressure induces enhanced atomic fluctuations in both holo-CaM/ligand complexes, but those of the holo-CaM/HVR complex seem to be larger. Thus, the inhibition of holo-CaM by TFP is supported by a low-volume ligand binding, albeit this is not associated with a rigidification of the complex structure on the sub-ns Å-scale.

Multiscale Characterization of Bacterial Swarming Illuminates Principles Governing Directed Surface Motility

Science.gov (United States)

Strickland, Ben; Hoeger, Kentaro; Ursell, Tristan

In many systems, individual characteristics interact, leading to the spontaneous emergence of order and complexity. In biological settings like microbes, such collective behaviors can imbue a variety of benefits to constituent individuals, including increased spatial range, improved access to nutrients, and enhanced resistance to antibiotic threats. To untangle the biophysical underpinnings of collective motility, we use passive tracers and a curated genetic library of Bacillus subtilis, including motile, non-motile, biofilm-deficient, and non-chemotactic mutants. We characterize and connect individual behavior on the microscopic scale to macroscopic colony morphology and motility of dendritic swarming. We analyze the persistence and dynamics of coordinated movement on length scales up to 4 orders of magnitude larger than that of individual cells, revealing rapid and directed responses of microbial groups to external stimuli, such as avoidance dynamics across chemical gradients. Our observations uncover the biophysical interplay between individual motility, surface wetness, phenotypic diversity, and external physical forces that robustly precipitate coordinated group behavior in microbes, and suggest general principles that govern the transition from individual to group behavior.

Towards ligand docking including explicit interface water molecules.

Directory of Open Access Journals (Sweden)

Gordon Lemmon

Full Text Available Small molecule docking predicts the interaction of a small molecule ligand with a protein at atomic-detail accuracy including position and conformation the ligand but also conformational changes of the protein upon ligand binding. While successful in the majority of cases, docking algorithms including RosettaLigand fail in some cases to predict the correct protein/ligand complex structure. In this study we show that simultaneous docking of explicit interface water molecules greatly improves Rosetta's ability to distinguish correct from incorrect ligand poses. This result holds true for both protein-centric water docking wherein waters are located relative to the protein binding site and ligand-centric water docking wherein waters move with the ligand during docking. Protein-centric docking is used to model 99 HIV-1 protease/protease inhibitor structures. We find protease inhibitor placement improving at a ratio of 9:1 when one critical interface water molecule is included in the docking simulation. Ligand-centric docking is applied to 341 structures from the CSAR benchmark of diverse protein/ligand complexes [1]. Across this diverse dataset we see up to 56% recovery of failed docking studies, when waters are included in the docking simulation.

Effect of ligand self-assembly on nanostructure and carrier transport behaviour in CdSe quantum dots

Energy Technology Data Exchange (ETDEWEB)

Li, Kuiying, E-mail: kuiyingli@ysu.edu.cn; Xue, Zhenjie

2014-11-14

Adjustment of the nanostructure and carrier behaviour of CdSe quantum dots (QDs) by varying the ligands used during QD synthesis enables the design of specific quantum devices via a self-assembly process of the QD core–shell structure without additional technologies. Surface photovoltaic (SPV) technology supplemented by X-ray diffractometry and infrared absorption spectroscopy were used to probe the characteristics of these QDs. Our study reveals that while CdSe QDs synthesized in the presence of and capped by thioglycolic acid, 3-mercaptopropionic acid, mercaptoethanol or α-thioglycerol ligands display zinc blende nanocrystalline structures, CdSe QDs modified by L-cysteine possess wurtzite nanocrystalline structures, because different end groups in these ligands induce distinctive nucleation and growth mechanisms. Carboxyl end groups in the ligand served to increase the SPV response of the QDs, when illuminated by hν ≥ E{sub g,nano-CdSe}. Increased length of the alkyl chains and side-chain radicals in the ligands partially inhibit photo-generated free charge carrier (FCC) transfer transitions of CdSe QDs illuminated by photon energy of 4.13 to 2.14 eV. The terminal hydroxyl group might better accommodate energy released in the non-radiative de-excitation process of photo-generated FCCs in the ligand's lowest unoccupied molecular orbital in the 300–580 nm wavelength region, when compared with other ligand end groups. - Highlights: • CdSe QDs modified by L-cysteine possess wurtzite nanocrystalline structures. • Carboxyl end groups in the ligand serve to increase the SPV response of CdSe QDs. • Terminal hydroxyl group in the ligand might accommodate non-radiative de-excitation process in CdSe QDs. • Increased length of the alkyl chains and side-chain radicals in the ligands partially inhibit carriers transport of CdSe QDs.

Determination of the surface area and sizes of supported copper nanoparticles through organothiol adsorption—ñhemisorption

Energy Technology Data Exchange (ETDEWEB)

Ndolomingo, Matumuene Joe; Meijboom, Reinout, E-mail: rmeijboom@uj.ac.za

2016-12-30

Highlights: • Cu on γ-Al{sub 2}O{sub 3} catalysts were prepared and characterized. • The ligand sorption-based technique was used for the determination of specific surface area and particle sizes. • The ligand packing density on Cu nanoparticles was quantified. • A fair agreement was found between the Cu particle sizes obtained from ligand adsorption and TEM methods. • The oxidation of morin by hydrogen peroxide was used to evaluate the catalytic activities of the Cu supported catalysts. - Abstract: The mechanisms involving the nanoparticle surfaces in catalytic reactions are more difficult to elucidate due to the nanoparticle surface unevenness, size distributions, and morphological irregularity. True surface area and particle sizes determination are key aspects of the activity of metal nanoparticle catalysts. Here we report on the organothiol adsorption-based technique for the determination of specific surface area of Cu nanoparticles, and their resultant sizes on γ-Al{sub 2}O{sub 3} supports. Quantification of ligand packing density on copper nanoparticles is also reported. The concentration of the probe ligand, 2-mercaptobenzimidazole (2-MBI) before and after immersion of supported copper catalysts was determined by ultraviolet-visible spectrometry (UV–vis). The amount of ligand adsorbed was found to be proportional to the copper nanoparticles surface area. Atomic absorption spectrometry (AAS), N{sub 2}-physisorption (BET), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) were used for the characterization of the catalysts. A fair agreement was found between particle sizes obtained from ligand adsorption and TEM methods. The catalytic activity of the copper nanoparticles related to their inherent surface area was evaluated using the model reaction of the oxidation of morin by hydrogen peroxide.

Crystallization of bi-functional ligand protein complexes.

Science.gov (United States)

Antoni, Claudia; Vera, Laura; Devel, Laurent; Catalani, Maria Pia; Czarny, Bertrand; Cassar-Lajeunesse, Evelyn; Nuti, Elisa; Rossello, Armando; Dive, Vincent; Stura, Enrico Adriano

2013-06-01

Homodimerization is important in signal transduction and can play a crucial role in many other biological systems. To obtaining structural information for the design of molecules able to control the signalization pathways, the proteins involved will have to be crystallized in complex with ligands that induce dimerization. Bi-functional drugs have been generated by linking two ligands together chemically and the relative crystallizability of complexes with mono-functional and bi-functional ligands has been evaluated. There are problems associated with crystallization with such ligands, but overall, the advantages appear to be greater than the drawbacks. The study involves two matrix metalloproteinases, MMP-12 and MMP-9. Using flexible and rigid linkers we show that it is possible to control the crystal packing and that by changing the ligand-enzyme stoichiometric ratio, one can toggle between having one bi-functional ligand binding to two enzymes and having the same ligand bound to each enzyme. The nature of linker and its point of attachment on the ligand can be varied to aid crystallization, and such variations can also provide valuable structural information about the interactions made by the linker with the protein. We report here the crystallization and structure determination of seven ligand-dimerized complexes. These results suggest that the use of bi-functional drugs can be extended beyond the realm of protein dimerization to include all drug design projects. Copyright © 2013 Elsevier Inc. All rights reserved.

Structure and function of the selectin ligand PSGL-1

Directory of Open Access Journals (Sweden)

Cummings R.D.

1999-01-01

Full Text Available P-selectin glycoprotein ligand-1 (PSGL-1 is a dimeric mucin-like 120-kDa glycoprotein on leukocyte surfaces that binds to P- and L-selectin and promotes cell adhesion in the inflammatory response. The extreme amino terminal extracellular domain of PSGL-1 is critical for these interactions, based on site-directed mutagenesis, blocking monoclonal antibodies, and biochemical analyses. The current hypothesis is that for high affinity interactions with P-selectin, PSGL-1 must contain O-glycans with a core-2 branched motif containing the sialyl Lewis x antigen (NeuAca2®3Galß1®4[Fuca1®3]GlcNAcß1®R. In addition, high affinity interactions require the co-expression of tyrosine sulfate on tyrosine residues near the critical O-glycan structure. This review addresses the biochemical evidence for this hypothesis and the evidence that PSGL-1 is an important in vivo ligand for cell adhesion.

Surface Patterning and Nanowire Biosensor Construction

DEFF Research Database (Denmark)

Iversen, Lars

2008-01-01

surface. A central limitation to this biosensor principle is the screening of analyte charge by mobile ions in electrolytes with physiological ionic strength. To overcome this problem, we propose to use as capture agents proteins which undergo large conformational changes. Using structure based protein...... charge prediction, we show how ligand induced changes in conformation of two model proteins, both being ligand binding domains from glutamate receptors, can lead to changes in electrostatic potential predicted to be sufficient for NW sensing. Finally we, demonstrate how InAs nanowires can....... In part I - “Surface Patterning” - glass and gold surfaces serve as spatially encoded immobilization supports for patterning of recombinant proteins and organic monolayers. First, we combine micro-contact printing with a reactive SNAP-tag protein to establish a general platform for templated protein...

Mixed-ligand Pt(II) dithione-dithiolato complexes: influence of the dicyanobenzodithiolato ligand on the second-order NLO properties.

Science.gov (United States)

Espa, Davide; Pilia, Luca; Marchiò, Luciano; Artizzu, Flavia; Serpe, Angela; Mercuri, Maria Laura; Simão, Dulce; Almeida, Manuel; Pizzotti, Maddalena; Tessore, Francesca; Deplano, Paola

2012-03-28

The mixed-ligand dithiolene complex [Pt(Bz(2)pipdt)(dcbdt)] (1) bearing the two ligands Bz(2)pipdt = 1,4-dibenzyl-piperazine-3,2-dithione and dcbdt = dicyanobenzodithiolato, has been synthesized, characterized and studied to evaluate its second-order optical nonlinearity. The dithione/dithiolato character of the two ligands gives rise to an asymmetric distribution of the charge in the molecule. This is reflected by structural data showing that in the C(2)S(2)PtS(2)C(2) dithiolene core the four sulfur atoms define a square-planar coordination environment of the metal where the Pt-S bond distances involving the two ligands are similar, while the C-S bond distances in the C(2)S(2) units exhibit a significant difference in Bz(2)pipdt (dithione) and dcbdt (dithiolato). 1 shows a moderately strong absorption peak in the visible region, which can be related to a HOMO-LUMO transition, where the dcbdt ligand (dithiolato) contributes mostly to the HOMO, and the Bz(2)pipdt one (dithione) mostly to the LUMO. Thus this transition has ligand-to-ligand charge transfer (CT) character with some contribution of the metal and undergoes negative solvatochromism and molecular quadratic optical nonlinearity (μβ(0) = -1296 × 10(-48) esu), which was determined by the EFISH (electric-field-induced second-harmonic generation) technique and compared with the values of similar complexes on varying the dithiolato ligand (mnt = maleonitriledithiolato, dmit = 2-thioxo-1,3-dithiole-4,5-dithiolato). Theoretical calculations help to elucidate the role of the dithiolato ligands in affecting the molecular quadratic optical nonlinearity of these complexes.

The role of the State in new governance: reinventing government ... again?

NARCIS (Netherlands)

van der Heijden, J.

2013-01-01

New environmental governance (NEG) gains momentum in addressing complex environmental problems. One of its bedrock principles is collaboration between state and non-state actors. Yet, what exactly does this collaboration look like? In scratching a bit deeper under the surface of the NEG literature

Role of ligands in permanganate oxidation of organics.

Science.gov (United States)

Jiang, Jin; Pang, Su-Yan; Ma, Jun

2010-06-01

We previously demonstrated that several ligands such as phosphate, pyrophosphate, EDTA, and humic acid could significantly enhance permanganate oxidation of triclosan (one phenolic biocide), which was explained by the contribution of ligand-stabilized reactive manganese intermediates in situ formed upon permanganate reduction. To further understand the underlying mechanism, we comparatively investigated the influence of ligands on permanganate oxidation of bisphenol A (BPA, one phenolic endocrine-disrupting chemical), carbamazepine (CBZ, a pharmaceutical containing the olefinic group), and methyl p-tolyl sulfoxide (TMSO, a typical oxygen-atom acceptor). Selected ligands exerted oxidation enhancement for BPA but had negligible influence for CBZ and TMSO. This was mainly attributed to the effects of identified Mn(III) complexes, which would otherwise disproportionate spontaneously in the absence of ligands. The one-electron oxidant Mn(III) species exhibited no reactivity toward CBZ and TMSO for which the two-electron oxygen donation may be the primary oxidation mechanism but readily oxidized BPA. The latter case was a function of pH, the complexing ligand, and the molar [Mn(III)]:[ligand] ratio, generally consistent with the patterns of ligand-affected permanganate oxidation. Moreover, the combination of the one-electron reduction of Mn(III) (Mn(III) + e(-) -->Mn(II)) and the Mn(VII)/Mn(II) reaction in excess ligands (Mn(VII) + 4Mn(II) ----> (ligands) 5Mn(III)) suggested a catalytic role of the Mn(III)/Mn(II) pair in permanganate oxidation of some phenolics in the presence of ligands.

Spatio-temporal Characterization of Ligand-Receptor Interactions in Blood Stem-Cell Rolling

KAUST Repository

Al Alwan, Bader

2017-08-16

One of the most important issues in the research on hematopoietic stem/progenitor cells (HSPCs) is to understand the mechanism of the homing process of these cells to the bone marrow after being transplanted into patients and establish the production of various blood cell types. The HSPCs first come in contact with the endothelial cells. This contact is known as adhesion and occurs through a multi-step paradigm ending with transmigration to the bone marrow niche. The initial step of the homing, tethering and rolling of HSPCs is mediated by P- and E-Selectins expressed on the endothelial cell surface through their interactions with the ligands expressed by HSPCs. Here we developed a novel experimental method to unravel the molecular mechanisms of the selectin-ligands interactions in vitro at the single molecule level by combining microfluidics and single-molecule fluorescence imaging. Our method enables direct visualization of the nanoscale spatiotemporal dynamics of the E-selectin-ligand (PSGL-1) interactions under conditions of shear stress acting on the cells at the molecular level in real time.

Determination of ligand binding modes in weak protein–ligand complexes using sparse NMR data

Energy Technology Data Exchange (ETDEWEB)

Mohanty, Biswaranjan; Williams, Martin L.; Doak, Bradley C.; Vazirani, Mansha; Ilyichova, Olga [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); Wang, Geqing [La Trobe University, La Trobe Institute for Molecular Bioscience (Australia); Bermel, Wolfgang [Bruker Biospin GmbH (Germany); Simpson, Jamie S.; Chalmers, David K. [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); King, Glenn F. [The University of Queensland, Institute for Molecular Bioscience (Australia); Mobli, Mehdi, E-mail: m.mobli@uq.edu.au [The University of Queensland, Centre for Advanced Imaging (Australia); Scanlon, Martin J., E-mail: martin.scanlon@monash.edu [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia)

2016-11-15

We describe a general approach to determine the binding pose of small molecules in weakly bound protein–ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of Ile, Leu, Val, Ala and Thr methyl groups using triple resonance scalar correlation data. The same sample may be used to obtain Met {sup ε}CH{sub 3} assignments using NOESY-based methods, although the superior sensitivity of NOESY using [U-{sup 13}C,{sup 15}N]-labeled protein makes the use of this second sample more efficient. We describe a structural model for a weakly binding ligand bound to its target protein, DsbA, derived from intermolecular methyl-to-ligand nuclear Overhauser enhancements, and demonstrate that the ability to assign all methyl resonances in the spectrum is essential to derive an accurate model of the structure. Once the methyl assignments have been obtained, this approach provides a rapid means to generate structural models for weakly bound protein–ligand complexes. Such weak complexes are often found at the beginning of programs of fragment based drug design and can be challenging to characterize using X-ray crystallography.

Fabrication and characterisation of ligand-functionalised ultrapure monodispersed metal nanoparticle nanoassemblies employing advanced gas deposition technique

Science.gov (United States)

Geremariam Welearegay, Tesfalem; Cindemir, Umut; Österlund, Lars; Ionescu, Radu

2018-02-01

Here, we report for the first time the fabrication of ligand-functionalised ultrapure monodispersed metal nanoparticles (Au, Cu, and Pt) from their pure metal precursors using the advanced gas deposition technique. The experimental conditions during nanoparticle formation were adjusted in order to obtain ultrafine isolated nanoparticles on different substrates. The morphology and surface analysis of the as-deposited metal nanoparticles were investigated using scanning electron microscopy, x-ray diffraction and Fourier transform infra-red spectroscopy, which demonstrated the formation of highly ordered pure crystalline nanoparticles with a relatively uniform size distribution of ∼10 nm (Au), ∼4 nm (Cu) and ∼3 nm (Pt), respectively. A broad range of organic ligands containing thiol or amine functional groups were attached to the nanoparticles to form continuous networks of nanoparticle-ligand nanoassemblies, which were characterised by scanning electron microscopy and x-ray photoelectron spectroscopy. The electrical resistance of the functional nanoassemblies deposited in the gap spacing of two microfabricated parallel Au electrodes patterned on silicon substrates ranged between tens of kΩ and tens of MΩ, which is suitable for use in many applications including (bio)chemical sensors, surface-enhanced Raman spectroscopy and molecular electronic rectifiers.

Contribution of Adsorbed Protein Films to Nanoscopic Vibrations Exhibited by Bacteria Adhering through Ligand-Receptor Bonds.

Science.gov (United States)

Song, Lei; Sjollema, Jelmer; Norde, Willem; Busscher, Henk J; van der Mei, Henny C

2015-09-29

Bacteria adhering to surfaces exhibit nanoscopic vibrations that depend on the viscoelasticity of the bond. The quantification of the nanoscopic vibrations of bacteria adhering to surfaces provides new opportunities to better understand the properties of the bond through which bacteria adhere and the mechanisms by which they resist detachment. Often, however, bacteria do not adhere to bare surfaces but to adsorbed protein films, on which adhesion involves highly specific ligand-receptor binding next to nonspecific DLVO interaction forces. Here we determine the contribution of adsorbed salivary protein and fibronectin films to vibrations exhibited by adhering streptococci and staphylococci, respectively. The streptococcal strain used has the ability to adhere to adsorbed salivary proteins films through antigen I/II ligand-receptor binding, while the staphylococcal strain used adheres to adsorbed fibronectin films through a proteinaceous ligand-receptor bond. In the absence of ligand-receptor binding, electrostatic interactions had a large impact on vibration amplitudes of adhering bacteria on glass. On an adsorbed salivary protein film, vibration amplitudes of adhering streptococci depended on the film softness as determined by QCM-D and were reduced after film fixation using glutaraldehyde. On a relatively stiff fibronectin film, cross-linking the film in glutaraldehyde hardly reduced its softness, and accordingly fibronectin film softness did not contribute to vibration amplitudes of adhering staphylococci. However, fixation of the staphylococcus-fibronectin bond further decreased vibration amplitudes, while fixation of the streptococcus bond hardly impacted vibration amplitudes. Summarizing, this study shows that both the softness of adsorbed protein films and the properties of the bond between an adhering bacterium and an adsorbed protein film play an important role in bacterial vibration amplitudes. These nanoscopic vibrations reflect the viscoelasticity of the

Radiation induced ligand loss from cobalt complexes

International Nuclear Information System (INIS)

Funston, A. M.; McFadyen, W.D.; Tregloan, P.A.

2000-01-01

Full text: Due to the rapid nature of ligand dissociation from cobalt(II) complexes the study of the rate of ligand dissociation necessitates the use of a technique such as pulse radiolysis. This allows the rapid reduction of the corresponding cobalt(III) complex by a reducing radical, such as the aquated electron, to form the cobalt(II) complex. However, to date, no systematic study of either the mechanism of reduction or the influence of the electronic structure on the rate of ligand dissociation has been carried out. In order to understand these processes more fully the mechanism of reduction of a range of related cobalt(III) complexes by the aquated electron and the subsequent rate of ligand dissociation from the resulting cobalt(II) complexes is being investigated. It has been found that a number of processes are observed following the initial rapid reaction of the cobalt(III) complex with the aquated electron. Ultimately ligand loss is observed. Depending upon the complex, the initial processes observed may include the formation of coordinated radicals and electron transfer within the complex. For complexes containing aromatic ligands such as 2,2'-bipyridine, 1,10-phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine the formation of a coordinated radical is observed as the initial reduction step. The kinetics of ligand dissociation of these complexes has been determined. The loss of monodentate ligands is fast and has been indistinguishable from the reduction processes when aromatic ligands are also present in the complex. However, for diamine chelates and diimine chelates spectra of the transient species can be resolved

Regulation mechanisms of the FLT3-ligand after irradiation; Mecanismes de regulation du FLT3-ligand apres irradiation

Energy Technology Data Exchange (ETDEWEB)

Prat-Lepesant, M

2005-06-15

The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia. The results indicated that the concentration of Flt3 ligand in the blood reflects the bone marrow status, and that the follow-up of plasma Flt3 ligand concentration could give predictive information about the bone marrow function and the duration and severity of pancytopenia and thrombocytopenia. Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. We thus developed a study in the mouse model. The results indicated that the variations in plasma Flt3 ligand variations were not solely due to a balance between its production by lymphoid cells and its consumption by hematopoietic cells. Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. These results also suggest that the Flt3 ligand is a main systemic regulator of hematopoiesis

Synthesis and characterization of mixed ligand chiral nanoclusters

KAUST Repository

Guven, Zekiye P.; Ustbas, Burcin; Harkness, Kellen M.; Coskun, Hikmet; Joshi, Chakra Prasad; Besong, Tabot M.D.; Stellacci, Francesco; Bakr, Osman; Akbulut, Ozge

2016-01-01

Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

Synthesis and characterization of mixed ligand chiral nanoclusters

KAUST Repository

Guven, Zekiye P.

2016-06-22

Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

Identifying Marine Copper-Binding Ligands in Seawater

Science.gov (United States)

Whitby, H.; Hollibaugh, J. T.; Maldonado, M. T.; Ouchi, S.; van den Berg, S. M.

2016-02-01

Complexation reactions are important because they affect the bioavailability of trace metals such as copper and iron. For example, organic complexation can determine whether copper is a limiting or a toxic micronutrient at natural levels. Copper competes with iron for complexing ligands, and when iron is limiting, copper can also substitute for iron in some metabolic pathways. The speciation of copper can be measured using complexing capacity titrations, which provide the concentration of individual ligand classes (L1, L2 etc.) and the complex stabilities (log K). Using methods recently developed in our laboratory, we show that the ligands within these classes can be measured independently of titrations, thus confirming the titration method and simultaneously identifying the ligands within each class. Thiols were identified as the L1 ligand class and humic compounds as the weaker L2 class in samples from coastal Georgia, USA, collected monthly from April to December. Log K values of the ligand complexes were consistent with values expected for thiols and humic substances. Recent results from culture studies and from samples collected along Line P, a coastal - oceanic transect in the HNLC region of the NE subarctic Pacific, will be presented in comparison to the estuarine results. This comparison will help to broaden our perspective on copper complexation and the ligands responsible, furthering our understanding of ligand sources and life cycles.

Ensemble Architecture for Prediction of Enzyme-ligand Binding Residues Using Evolutionary Information.

Science.gov (United States)

Pai, Priyadarshini P; Dattatreya, Rohit Kadam; Mondal, Sukanta

2017-11-01

Enzyme interactions with ligands are crucial for various biochemical reactions governing life. Over many years attempts to identify these residues for biotechnological manipulations have been made using experimental and computational techniques. The computational approaches have gathered impetus with the accruing availability of sequence and structure information, broadly classified into template-based and de novo methods. One of the predominant de novo methods using sequence information involves application of biological properties for supervised machine learning. Here, we propose a support vector machines-based ensemble for prediction of protein-ligand interacting residues using one of the most important discriminative contributing properties in the interacting residue neighbourhood, i. e., evolutionary information in the form of position-specific- scoring matrix (PSSM). The study has been performed on a non-redundant dataset comprising of 9269 interacting and 91773 non-interacting residues for prediction model generation and further evaluation. Of the various PSSM-based models explored, the proposed method named ROBBY (pRediction Of Biologically relevant small molecule Binding residues on enzYmes) shows an accuracy of 84.0 %, Matthews Correlation Coefficient of 0.343 and F-measure of 39.0 % on 78 test enzymes. Further, scope of adding domain knowledge such as pocket information has also been investigated; results showed significant enhancement in method precision. Findings are hoped to boost the reliability of small-molecule ligand interaction prediction for enzyme applications and drug design. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Substrate coated with receptor and labelled ligand for assays

International Nuclear Information System (INIS)

1980-01-01

Improvements in the procedures for assaying ligands are described. The assay consists of a polystyrene tube on which receptors are present for both the ligand to be assayed and a radioactively labelled form of the ligand. The receptors on the bottom portion of the tube are also coated with labelled ligands, thus eliminating the necessity for separate addition of the labelled ligand and sample during an assay. Examples of ligands to which this method is applicable include polypeptides, nucleotides, nucleosides and proteins. Specific examples are given in which the ligand to be assayed is digoxin, the labelled form of the ligand is 3-0-succinyl digoxyigenin tyrosine ( 125 I) and the receptor is digoxin antibody. (U.K.)

Colloidal nanoparticle size control: experimental and kinetic modeling investigation of the ligand-metal binding role in controlling the nucleation and growth kinetics.

Science.gov (United States)

Mozaffari, Saeed; Li, Wenhui; Thompson, Coogan; Ivanov, Sergei; Seifert, Soenke; Lee, Byeongdu; Kovarik, Libor; Karim, Ayman M

2017-09-21

Despite the major advancements in colloidal metal nanoparticles synthesis, a quantitative mechanistic treatment of the ligand's role in controlling their size remains elusive. We report a methodology that combines in situ small angle X-ray scattering (SAXS) and kinetic modeling to quantitatively capture the role of ligand-metal binding (with the metal precursor and the nanoparticle surface) in controlling the synthesis kinetics. We demonstrate that accurate extraction of the kinetic rate constants requires using both, the size and number of particles obtained from in situ SAXS to decouple the contributions of particle nucleation and growth to the total metal reduction. Using Pd acetate and trioctylphosphine in different solvents, our results reveal that the binding of ligands with both the metal precursor and nanoparticle surface play a key role in controlling the rates of nucleation and growth and consequently the final size. We show that the solvent can affect the metal-ligand binding and consequently ligand coverage on the nanoparticles surface which has a strong effect on the growth rate and final size (1.4 nm in toluene and 4.3 nm in pyridine). The proposed kinetic model quantitatively predicts the effects of varying the metal concentration and ligand/metal ratio on nanoparticle size for our work and literature reports. More importantly, we demonstrate that the final size is exclusively determined by the nucleation and growth kinetics at early times and not how they change with time. Specifically, the nanoparticle size in this work and many literature reports can be predicted using a single, model independent kinetic descriptor, (growth-to-nucleation rate ratio) 1/3 , despite the different metals and synthetic conditions. The proposed model and kinetic descriptor could serve as powerful tools for the design of colloidal nanoparticles with specific sizes.

High photoreactivity in a non-fluorescent photocleavable ligands on gold

Science.gov (United States)

Robinson, Hans D.; Daengngam, Chalongrat; Stoianov, Stefan V.; Thorpe, Steven B.; Guo, Xi; Santos, Webster L.; Morris, John R.

2014-03-01

We report on the photo-patterning of a gold surface functionalized with a self-assembled monolayer of an o-nitrobenzyl-based photocleavable ligand bound to the gold surface with a thiol anchor. We find that the dose of UV light required to induce the photoreaction on gold is very similar to the dose in an alcohol solution, even though many optical phenomena are strongly suppressed on metal surfaces. We attribute this finding to a combination of the large skin depth in gold at UV wavelengths, the high speed of the photoreaction, and the spatially indirect nature of the lowest excited singlet. Any photoreactive compound where the quantum efficiency of fluorescence is sufficiently low, preferably no larger than about 10-5 in the case of gold surfaces, will show a similarly high photoreactivity in metal-surface monolayers. The implications of this result for optically driven self-assembly in plasmonic systems will be discussed. This work was supported by a grant from the National Science Foundation (DMR-106753).

Correcting binding parameters for interacting ligand-lattice systems

Science.gov (United States)

Hervy, Jordan; Bicout, Dominique J.

2017-07-01

Binding of ligands to macromolecules is central to many functional and regulatory biological processes. Key parameters characterizing ligand-macromolecule interactions are the stoichiometry, inducing the number of ligands per macromolecule binding site, and the dissociation constant, quantifying the ligand-binding site affinity. Both these parameters can be obtained from analyses of classical saturation experiments using the standard binding equation that offers the great advantage of mathematical simplicity but becomes an approximation for situations of interest when a ligand binds and covers more than one single binding site on the macromolecule. Using the framework of car-parking problem with latticelike macromolecules where each ligand can cover simultaneously several consecutive binding sites, we showed that employing the standard analysis leads to underestimation of binding parameters, i.e., ligands appear larger than they actually are and their affinity is also greater than it is. Therefore, we have derived expressions allowing to determine the ligand size and true binding parameters (stoichiometry and dissociation constant) as a function of apparent binding parameters retrieved from standard saturation experiments.

THERMODYNAMICS OF PROTEIN-LIGAND INTERACTIONS AND THEIR ANALYSIS

Directory of Open Access Journals (Sweden)

Rummi Devi Saini

2017-11-01

Full Text Available Physiological processes are controlled mainly by intermolecular recognition mechanisms which involve protein–protein and protein–ligand interactions with a high specificity and affinity to form a specific complex. Proteins being an important class of macromolecules in biological systems, it is important to understand their actions through binding to other molecules of proteins or ligands. In fact, the binding of low molecular weight ligands to proteins plays a significant role in regulating biological processes such as cellular metabolism and signal transmission. Therefore knowledge of the protein–ligand interactions and the knowledge of the mechanisms involved in the protein-ligand recognition and binding are key in understanding biology at molecular level which will facilitate the discovery, design, and development of drugs. In this review, the mechanisms involved in protein–ligand binding, the binding kinetics, thermodynamic concepts and binding driving forces are discussed. Thermodynamic mechanisms involved in a few important protein-ligand binding are described. Various spectroscopic, non-spectroscopic and computational method for analysis of protein–ligand binding are also discussed.

Lanthanides and actinides sorption on to alumina with simple organic ligands. Thermodynamic and spectroscopic approaches

International Nuclear Information System (INIS)

Alliot, C.

2003-01-01

This work comes within studies of nuclear waste disposal. The sorption of radionuclide onto mineral is very important to understand their migration. So this work deals with the influence of ligands like oxalic, acetic and carbonic acids on lanthanides and actinides sorption onto alumina. Two complementary approaches were carried out: thermodynamic (determination of chemical reactions and associated constants). So we obtain a thermodynamic database for the ternary systems metal/ligand/alumina which we use to define the experimental conditions to observe by spectroscopy sorbed species. Then the identification of surface complexes was carried out using two spectroscopies, XPS and TRLIFS. (author)

Development of immobilized ligands for actinide separations

International Nuclear Information System (INIS)

Paine, R.T.

1994-01-01

Primary goals during this grant period were to (1) synthesize new bifunctional chelating ligands, (2) characterize the structural features of the Ln and An coordination complexes formed by these ligands, (3) use structural data to iteratively design new classes of multifunctional ligands, and (4) explore additional routes for attachment of key ligands to solid supports that could be useful for chromatographic separations. Some highlights of recently published work as well as a summary of submitted, unpublished and/or still in progress research are outlined

Entangled zinc-ditetrazolate frameworks involving in situ ligand synthesis and topological modulation by various secondary N-donor ligands

International Nuclear Information System (INIS)

Li Yunwu; Chen Weilin; Wang Yonghui; Li Yangguang; Wang Enbo

2009-01-01

The introduction of various secondary N-donor ligands into an in situ ditetrazolate-ligand synthesis system of terephthalonitrile, NaN 3 and ZnCl 2 led to the formation of three new entangled frameworks Zn(pdtz)(4,4'-bipy).3H 2 O (1), [Zn(pdtz)(bpp)] 2 .3H 2 O (2) and Zn(pdtz) 0.5 (N 3 )(2,2'-bipy) (3) (4,4'-bipy=4,4'-bipyridine; bpp=1,3-bis(4-pyridyl)propane; 2,2'-bipy=2,2'-bipyridine; H 2 pdtz=5,5'-1,4-phenylene-ditetrazole). The formation of pdtz 2- ligand involves the Sharpless [2+3] cycloaddition reaction between terephthalonitrile and NaN 3 in the presence of Zn 2+ ion as a Lewis-acid catalyst under hydrothermal conditions. Compound 1 exhibits a fivefold interpenetrating 3D framework based on the diamondoid topology. Compound 2 displays a twofold parallel interpenetrating framework based on the wavelike individual network. Compound 3 possesses a 2D puckered network. These new Zn-ditetrazolate frameworks are highly dependent on the modulation of different secondary N-donor ligands. Their luminescent properties were investigated. - Graphical abstract: Three new entangled frameworks were prepared by an in situ ditetrazolate-ligand synthesis system assisted with various auxiliary N-donor ligands. The entangled structures can be modulated by different secondary ligands.

Selective extraction of trivalent actinides with hard-soft mixed donor ligands: role of intra-ligand synergism

International Nuclear Information System (INIS)

Ghanty, Tapan K.

2016-01-01

In recent years, considerable attention has been given to understand the coordination chemistry of trivalent lanthanide (Ln) and actinide (An) with various ligands because of its close link with the nuclear waste management processes. It is well known that lanthanide-actinide separation is a challenging and difficult task because of very similar chemical properties of these two series of ions, which are associated with similar ionic radii and coordination numbers. Recently, we have introduced a new concept, 'intra-ligand synergism', where hard donor atom, such as, oxygen preferentially binds to trivalent actinides (An(III)) as compared to the valence iso-electronic trivalent lanthanides (Ln(III)) in presence of another soft donor centre. In the present work, the conventional concept of selective complexation of actinides with soft donor ligands (either S or N donor) has been modified through exploiting this concept, and thereby the higher selectivity of 1,10-phenanthroline-2,9-dicarboxylamide (PDAM) based ligands, namely PDAM and its isobutyl and decyl derivatives towards Am(III) ion has been predicted theoretically through density functional calculations. Subsequently, several such amide derivatives have been synthesized to optimize the solubility of the ligands in organic phase. Finally, solvent extraction experiments have been carried out to validate the theoretical prediction on the selectivity of oxygen donor ligands towards Am(III) as compared to Eu(III), and a maximum separation factor of about 51 has been achieved experimentally using 2,9-bis(N-decylaminocarbonyl)-1,10-phenanthroline ligand. The separation factor is increased with the decrease in pH, which is very interesting since extraction of the Am 3+ ion is considered to be important under highly acidic conditions from the nuclear waste management point of view. (author)

Synthesis, spectral, thermal and biological studies of mixed ligand complexes with newly prepared Schiff base and 1,10-phenanthroline ligands

Science.gov (United States)

Abd El-Halim, Hanan F.; Mohamed, Gehad G.; Khalil, Eman A. M.

2017-10-01

A series of mixed ligand complexes were prepared from the Schiff base (L1) as a primary ligand, prepared by condensation of oxamide and furan-2-carbaldehyde, and 1,10-phenanthroline (1,10-phen) as a secondary ligand. The Schiff base ligand and its mixed ligand chelates were characterized based on elemental analysis, IR, 1H NMR, thermal analysis, UV-Visible, mass, molar conductance, magnetic moment. X-ray diffraction, solid reflectance and ESR also have been studied. The mixed ligand complexes were found to have the formulae of [M(L1) (1,10-phen)]Clm.nH2O (M = Cr(III) and Fe(III) (m = 3) (n = 0); M = Mn(II), Cu(II) and Cd(II) (m = 2) (n = 0); and M = Co(II) (m = 2) (n = 1), Ni(II) (m = 2) (n = 2) and Zn(II) (m = 2) (n = 3)) and that the geometrical structure of the complexes were octahedral. The parameters of thermodynamic using Coats-Redfern and Horowitz-Metzger equations were calculated. The synthesized Schiff base ligand, 1,10-phenanthroline ligand and Their mixed ligand complexes were also investigated for their antibacterial and antifungal activity against bacterial species (Gram-Ve bacteria: Pseudomonas aeruginosa and Escherichia coli) and (Gram + Ve bacteria: Bacillus subtilis and Streptococcus pneumonia) and fungi (Aspergillus fumigates and Candida albicans). The anticancer activity of the new compounds had been tested against breast (MFC7) and colon (HCT-116) cell lines. The results showed high activity for the synthesized compounds.

Dockomatic - automated ligand creation and docking.

Science.gov (United States)

Bullock, Casey W; Jacob, Reed B; McDougal, Owen M; Hampikian, Greg; Andersen, Tim

2010-11-08

The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI) application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

Dockomatic - automated ligand creation and docking

Directory of Open Access Journals (Sweden)

Hampikian Greg

2010-11-01

Full Text Available Abstract Background The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. Results DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. Conclusions DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

A simplified model for dynamics of cell rolling and cell-surface adhesion

International Nuclear Information System (INIS)

Cimrák, Ivan

2015-01-01

We propose a three dimensional model for the adhesion and rolling of biological cells on surfaces. We study cells moving in shear flow above a wall to which they can adhere via specific receptor-ligand bonds based on receptors from selectin as well as integrin family. The computational fluid dynamics are governed by the lattice-Boltzmann method. The movement and the deformation of the cells is described by the immersed boundary method. Both methods are fully coupled by implementing a two-way fluid-structure interaction. The adhesion mechanism is modelled by adhesive bonds including stochastic rules for their creation and rupture. We explore a simplified model with dissociation rate independent of the length of the bonds. We demonstrate that this model is able to resemble the mesoscopic properties, such as velocity of rolling cells

Surface enhanced Raman spectroscopy detection of biomolecules using EBL fabricated nanostructured substrates.

Science.gov (United States)

Peters, Robert F; Gutierrez-Rivera, Luis; Dew, Steven K; Stepanova, Maria

2015-03-20

Fabrication and characterization of conjugate nano-biological systems interfacing metallic nanostructures on solid supports with immobilized biomolecules is reported. The entire sequence of relevant experimental steps is described, involving the fabrication of nanostructured substrates using electron beam lithography, immobilization of biomolecules on the substrates, and their characterization utilizing surface-enhanced Raman spectroscopy (SERS). Three different designs of nano-biological systems are employed, including protein A, glucose binding protein, and a dopamine binding DNA aptamer. In the latter two cases, the binding of respective ligands, D-glucose and dopamine, is also included. The three kinds of biomolecules are immobilized on nanostructured substrates by different methods, and the results of SERS imaging are reported. The capabilities of SERS to detect vibrational modes from surface-immobilized proteins, as well as to capture the protein-ligand and aptamer-ligand binding are demonstrated. The results also illustrate the influence of the surface nanostructure geometry, biomolecules immobilization strategy, Raman activity of the molecules and presence or absence of the ligand binding on the SERS spectra acquired.

Post-colonial governance through securitization?

DEFF Research Database (Denmark)

Rasmussen, Rasmus Kjærgaard; Merkelsen, Henrik

2017-01-01

This article combines the securitization approach with theory of risk and narratological methodology in the analysis of the Danish-Greenlandic government debates about potential uranium exploitation. The authors conclude that the securitization controversy visible at the surface level of policy...... documents reflects an identity struggle at the deeper narrative level closely related to the understanding of national identity politics. These underlying stakes are brought to the fore when securitization is used as a governance technique....

Molecular Characterization of the Interactions between Vascular Selectins and Glycoprotein Ligands on Human Hematopoietic Stem/Progenitor Cells

KAUST Repository

Abusamra, Dina

2016-12-01

The human bone marrow vasculature constitutively expresses both E-selectin and P-selectin where they interact with the cell-surface glycan moiety, sialyl Lewis x, on circulating hematopoietic stem/progenitor cells (HSPCs) to mediate the essential tethering/rolling step. Although several E-selectin glycoprotein ligands (E-selLs) have been identified, the importance of each E-selL on human HSPCs is debatable and requires additional methodologies to advance their specific involvement. The first objective was to fill the knowledge gap in the in vitro characterization of the mechanisms used by selectins to mediate the initial step in the HSPCs homing by developing a real time immunoprecipitation-based assay on a surface plasmon resonance chip. This novel assay bypass the difficulties of purifying ligands, enables the use of natively glycosylated forms of selectin ligands from any model cell of interest and study its binding affinities under flow. We provide the first comprehensive quantitative binding kinetics of two well-documented ligands, CD44 and PSGL-1, with E-selectin. Both ligands bind monomeric E-selectin transiently with fast on- and off-rates while they bind dimeric E-selectin with remarkably slow on- and off-rates with the on-rate, but not the off-rate, is dependent on salt concentration. Thus, suggest a mechanism through which monomeric selectins mediate initial fast-on and -off binding to capture the circulating cells out of shear-flow; subsequently, tight binding by dimeric/oligomeric selectins is enabled to slow rolling significantly. The second objective is to fully identify and characterize E/P-selectin ligand candidates expressed on CD34+ HSPCs which cause enhanced migration after intravenous transplantation compared to their CD34- counterparts. CD34 is widely recognized marker of human HSPCs but its natural ligand and function on these cells remain elusive. Proteomics identified CD34 as an E-selL candidate on human HSPCs, whose binding to E

Effects of the capping ligands, linkers and oxide surface on the electron injection mechanism of copper sulfide quantum dot-sensitized solar cells.

Science.gov (United States)

Suárez, Javier Amaya; Plata, Jose J; Márquez, Antonio M; Sanz, Javier Fdez

2017-06-07

Quantum dot-sensitized solar cells, QDSCs, are a clean and effective alternative to fossil fuels to reduce CO 2 emissions. However, the different components that constitute the QDSCs and the difficulty of isolating experimentally their effects on the performance of the whole system slow down the development of more efficient devices. In this work, DFT calculations are combined with a bottom-up approach to differentiate the effect of each component on the electronic structure and absorption spectra. First, Cu 2 S QDs were built including a U parameter to effectively describe the localization of electrons. The effect of capping agents is addressed using ligands with different electron-donating/withdrawing groups. The role of linkers and their adsorption on the oxide surface are also examined. Finally, we propose a main indirect electron injection mechanism based on the position of the peaks of the spectra.

Determination of the surface density of polyethylene glycol on gold nanoparticles by use of microscale thermogravimetric analysis.

Science.gov (United States)

Sebby, K B; Mansfield, E

2015-04-01

The widespread integration of nanoparticle technologies into biomedicine will depend on the ability to repeatedly create particles with well-defined properties and predictable behaviors. For this to happen, fast, reliable, inexpensive, and widely available techniques to characterize nanomaterials are needed. Characterization of the surface molecules is particularly important since the surface, including the surface molecule density, plays a dominant role in determining how nanoparticles interact with their surroundings. Here, 10 and 30 nm gold nanoparticle NIST Standard Reference Materials were functionalized with fluorescently labeled polyethylene glycol (PEG) with either thiolate or lipoic acid anchoring groups to evaluate analytical techniques for determining surface coverage. The coating of the nanoparticles was confirmed with dynamic light scattering, microscale thermogravimetric analysis (μ-TGA), and ultraviolet-visible (UV-vis) spectroscopy. A UV-vis method for determining gold nanoparticle concentrations that takes into account spectral broadening upon functionalization was developed. The amount of bound PEG was quantified with μ-TGA, a technique analogous to thermogravimetric analysis that uses quartz crystal microbalances, and fluorescence spectroscopy of displaced ligands. It is shown that μ-TGA is a convenient technique for the quantification of ligands bound to inorganic particles while sacrificing a minimal amount of sample, and the treatment of the functionalized nanoparticle dispersions with dithiothreitol may be insufficient to achieve complete displacement of the surface ligands for quantification by fluorescence measurements. The μ-TGA and fluorescence results were used to determine ligand footprint sizes-average areas occupied by each ligand on the particles' surface. The lipoic acid bound ligands had footprint sizes of 0.21 and 0.25 nm(2) on 10 and 30 nm particles, respectively while the thiolate ligands had footprint sizes of 0.085 and 0

Synthesis of novel '4+1' Tc(III)/Re(III) mixed-ligand complexes with dendritically modified ligands

International Nuclear Information System (INIS)

Gniazdowska, E.; Kuenstler, J.U.; Stephan, H.; Pietzsch, H.J.

2006-01-01

Coordination chemistry of technetium and rhenium attracts a considerable interest due to the nuclear medicine applications of their radionuclides. Inert, so-called '3+1' or '4+1' technetium/rhenium mixed-ligand complexes open a new way to application of 99 mTc/ 188 Re labeled compounds in tumor diagnosis and therapy. In the presented paper, authors describe the synthesis and study of novel 99 mTc/ 188 Re complexes with dendritically functionalized tetradentate (tripodal chelator 2,2',2''-nitrilotris(ethanethiol), NS 3 and carboxyl group-bearing ligand, NS 3 (COOH) 3 ) and monodentate (dendritically modified isocyanide, CN-R(COOMe) 3 and isocyanide-modified peptide, CN-GGY) ligands. To verify the identity of the prepared n.c.a. complexes, non-radioactive analogous '4+1' Re compounds were synthesized. The experimental data show that a dendritic modification of the tetradentate/monodentate ligands changes the complex lipophilicity and does not influence its stability

Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain.

Science.gov (United States)

Runge, Steffen; Thøgersen, Henning; Madsen, Kjeld; Lau, Jesper; Rudolph, Rainer

2008-04-25

The glucagon-like peptide-1 receptor (GLP-1R) belongs to Family B1 of the seven-transmembrane G protein-coupled receptors, and its natural agonist ligand is the peptide hormone glucagon-like peptide-1 (GLP-1). GLP-1 is involved in glucose homeostasis, and activation of GLP-1R in the plasma membrane of pancreatic beta-cells potentiates glucose-dependent insulin secretion. The N-terminal extracellular domain (nGLP-1R) is an important ligand binding domain that binds GLP-1 and the homologous peptide Exendin-4 with differential affinity. Exendin-4 has a C-terminal extension of nine amino acid residues known as the "Trp cage", which is absent in GLP-1. The Trp cage was believed to interact with nGLP-1R and thereby explain the superior affinity of Exendin-4. However, the molecular details that govern ligand binding and specificity of nGLP-1R remain undefined. Here we report the crystal structure of human nGLP-1R in complex with the antagonist Exendin-4(9-39) solved by the multiwavelength anomalous dispersion method to 2.2A resolution. The structure reveals that Exendin-4(9-39) is an amphipathic alpha-helix forming both hydrophobic and hydrophilic interactions with nGLP-1R. The Trp cage of Exendin-4 is not involved in binding to nGLP-1R. The hydrophobic binding site of nGLP-1R is defined by discontinuous segments including primarily a well defined alpha-helix in the N terminus of nGLP-1R and a loop between two antiparallel beta-strands. The structure provides for the first time detailed molecular insight into ligand binding of the human GLP-1 receptor, an established target for treatment of type 2 diabetes.

Bexarotene ligand pharmaceuticals.

Science.gov (United States)

Hurst, R E

2000-12-01

Bexarotene (LGD-1069), from Ligand, was the first retinoid X receptor (RXR)-selective, antitumor retinoid to enter clinical trials. The company launched the drug for the treatment of cutaneous T-cell lymphoma (CTCL), as Targretin capsules, in the US in January 2000 [359023]. The company filed an NDA for Targretin capsules in June 1999, and for topical gel in December 1999 [329011], [349982] specifically for once-daily oral administration for the treatment of patients with early-stage CTCL who have not tolerated other therapies, patients with refractory or persistent early stage CTCL and patients with refractory advanced stage CTCL. The FDA approved Targretin capsules at the end of December 1999 for once-daily oral treatment of all stages of CTCL in patients refractory to at least one prior systemic therapy, at an initial dose of 300 mg/m2/day. After an NDA was submitted in December 1999 for Targretin gel, the drug received Priority Review status for use as a treatment of cutaneous lesions in patients with stage IA, IB or IIA CTCL [354836]. The FDA issued an approvable letter in June 2000, and granted marketing clearance for CTCL in the same month [370687], [372768], [372769], [373279]. Ligand had received Orphan Drug designation for this indication [329011]. At the request of the FDA, Ligand agreed to carry out certain post-approval phase IV and pharmacokinetic studies [351604]. The company filed an MAA with the EMEA for Targretin Capsules to treat lymphoma in November 1999 [348944]. The NDA for Targretin gel is based on a multicenter phase III trial that was conducted in the US, Canada, Europe and Australia involving 50 patients and a multicenter phase I/II clinical program involving 67 patients. Targretin gel was evaluated for the treatment of patients with early stage CTCL (IA-IIA) who were refractory to, intolerant to, or reached a response plateau for at least 6 months on at least two prior therapies. Efficacy results exceeded the protocol-defined response

Protein-scaffold Directed Nanoscale Assembly of T Cell Ligands: Artificial Antigen Presentation with Defined Valency, Density and Ratio.

Science.gov (United States)

Smith, Mason R; Tolbert, Stephanie V; Wen, Fei

2018-05-07

Tuning antigen presentation to T cells is a critical step in investigating key aspects of T cell activation. However, existing technologies have limited ability to control the spatial and stoichiometric organization of T cell ligands on 3D surfaces. Here, we developed an artificial antigen presentation platform based on protein-scaffold directed assembly that allows fine control over the spatial and stoichiometric organization of T cell ligands on a 3D yeast-cell surface. Using this system, we observed that the T cell activation threshold on a 3D surface is independent of peptide-major histocompatibility complex (pMHC) valency, but instead determined by the overall pMHC surface density. When intercellular adhesion molecule 1 (ICAM-1) was co-assembled with pMHC, it enhanced antigen recognition sensitivity by 6-fold. Further, T cells responded with different magnitudes to varying ratios of pMHC and ICAM-1 and exhibited a maximum response at a ratio of 15% pMHC and 85% ICAM-1, introducing an additional parameter for tuning T cell activation. This protein-scaffold directed assembly technology is readily transferrable to acellular surfaces for translational research as well as large-scale T-cell manufacturing.

Ligand exchange chromatography of free amino acids and proteins on porous microparticulate zirconium oxide

International Nuclear Information System (INIS)

Blackwell, J.A.; Carr, P.W.

1992-01-01

The Lewis acid sites present on the underlying zirconium oxide particles are responsible for the unusual elution sequence for amino acids on copper loaded, phosphated zirconium oxide supports reported in an earlier study. To more thoroughly examine the effect of these strong Lewis acid sites in this paper. The authors have studied ligand exchange chromatography on copper loaded zirconium oxide particles. It is shown here that carboxylate functional groups on amino acid solutes strongly interact with surface Lewis acid sites. Addition of competing hard Lewis bases to the eluent attenuates these specific interactions. The result is a chromatographic system with high selectivity which is also suitable for ligand exchange chromatography of proteins

Synthesis and characterization β-ketoamine ligands

Science.gov (United States)

Zaid, Nurzati Amani Mohamed; Hassan, Nur Hasyareeda; Karim, Nurul Huda Abd

2018-04-01

β-ketoamine ligands are important members of heterodonor ligand because of their ease of preparation and modification of both steric and/or electronic effects. Complexes with β-ketoamine has received much less attention and there has been no study about this complex with β-ketoamine in ionic liquid reported. Two type of β-ketoamine ligands which are 4-amino-3-pentene-2-onato (A) and 3-amino-2-butenoic acid methyl ester (B) have been synthesized in this work. The resulting compound formed was characterized using standard spectroscopic and structural techniques which includes 1H and 13C, NMR spectroscopy and FTIR spectroscopy. The 1H and 13C NMR spectrum displayed all the expected signals with correct integration and multiplicity. And it is proved that there are some differences between two ligands as observed in NMR and FTIR spectrum.

Expression Profiles of Ligands for Activating Natural Killer Cell Receptors on HIV Infected and Uninfected CD4⁺ T Cells.

Science.gov (United States)

Tremblay-McLean, Alexandra; Bruneau, Julie; Lebouché, Bertrand; Lisovsky, Irene; Song, Rujun; Bernard, Nicole F

2017-10-12

Natural Killer (NK) cell responses to HIV-infected CD4 T cells (iCD4) depend on the integration of signals received through inhibitory (iNKR) and activating NK receptors (aNKR). iCD4 activate NK cells to inhibit HIV replication. HIV infection-dependent changes in the human leukocyte antigen (HLA) ligands for iNKR on iCD4 are well documented. By contrast, less is known regarding the HIV infection related changes in ligands for aNKR on iCD4. We examined the aNKR ligand profiles HIV p24⁺ HIV iCD4s that maintained cell surface CD4 (iCD4⁺), did not maintain CD4 (iCD4 - ) and uninfected CD4 (unCD4) T cells for expression of unique long (UL)-16 binding proteins-1 (ULBP-1), ULBP-2/5/6, ULBP-3, major histocompatibility complex (MHC) class 1-related (MIC)-A, MIC-B, CD48, CD80, CD86, CD112, CD155, Intercellular adhesion molecule (ICAM)-1, ICAM-2, HLA-E, HLA-F, HLA-A2, HLA-C, and the ligands to NKp30, NKp44, NKp46, and killer immunoglobulin-like receptor 3DS1 (KIR3DS1) by flow cytometry on CD4 T cells from 17 HIV-1 seronegative donors activated and infected with HIV. iCD4⁺ cells had higher expression of aNKR ligands than did unCD4. However, the expression of aNKR ligands on iCD4 where CD4 was downregulated (iCD4 - ) was similar to (ULBP-1, ULBP-2/5/6, ULBP-3, MIC-A, CD48, CD80, CD86 and CD155) or significantly lower than (MIC-B, CD112 and ICAM-2) what was observed on unCD4. Thus, HIV infection can be associated with increased expression of aNKR ligands or either baseline or lower than baseline levels of aNKR ligands, concomitantly with the HIV-mediated downregulation of cell surface CD4 on infected cells.

A2A adenosine receptor ligand binding and signalling is allosterically modulated by adenosine deaminase.

Science.gov (United States)

Gracia, Eduard; Pérez-Capote, Kamil; Moreno, Estefanía; Barkešová, Jana; Mallol, Josefa; Lluís, Carme; Franco, Rafael; Cortés, Antoni; Casadó, Vicent; Canela, Enric I

2011-05-01

A2ARs (adenosine A2A receptors) are highly enriched in the striatum, which is the main motor control CNS (central nervous system) area. BRET (bioluminescence resonance energy transfer) assays showed that A2AR homomers may act as cell-surface ADA (adenosine deaminase; EC 3.5.4.4)-binding proteins. ADA binding affected the quaternary structure of A2ARs present on the cell surface. ADA binding to adenosine A2ARs increased both agonist and antagonist affinity on ligand binding to striatal membranes where these proteins are co-expressed. ADA also increased receptor-mediated ERK1/2 (extracellular-signal-regulated kinase 1/2) phosphorylation. Collectively, the results of the present study show that ADA, apart from regulating the concentration of extracellular adenosine, may behave as an allosteric modulator that markedly enhances ligand affinity and receptor function. This powerful regulation may have implications for the physiology and pharmacology of neuronal A2ARs.

Designer TGFβ superfamily ligands with diversified functionality.

Directory of Open Access Journals (Sweden)

George P Allendorph

Full Text Available Transforming Growth Factor--beta (TGFβ superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs, and Bone Morphogenetic Proteins (BMPs, are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer, to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFβ superfamily ligands through development of novel chimeric TGFβ ligands with diverse biological and clinical values.

Prediction of GPCR-Ligand Binding Using Machine Learning Algorithms

Directory of Open Access Journals (Sweden)

Sangmin Seo

2018-01-01

Full Text Available We propose a novel method that predicts binding of G-protein coupled receptors (GPCRs and ligands. The proposed method uses hub and cycle structures of ligands and amino acid motif sequences of GPCRs, rather than the 3D structure of a receptor or similarity of receptors or ligands. The experimental results show that these new features can be effective in predicting GPCR-ligand binding (average area under the curve [AUC] of 0.944, because they are thought to include hidden properties of good ligand-receptor binding. Using the proposed method, we were able to identify novel ligand-GPCR bindings, some of which are supported by several studies.

New pinene-derived pyridines as bidentate chiral ligands

Czech Academy of Sciences Publication Activity Database

Malkov, A. V.; Stewart-Liddon, A.; Teplý, Filip; Kobr, L.; Muir, K. W.; Haigh, D.; Kočovský, P.

2008-01-01

Roč. 64, č. 18 (2008), s. 4011-4025 ISSN 0040-4020 Institutional research plan: CEZ:AV0Z40550506 Keywords : chiral ligands * transition metal catalysis * asymmetric catalysis * pyridine ligands * oxazoline ligands Subject RIV: CC - Organic Chemistry Impact factor: 2.897, year: 2008

Fine-tuning the Wall Thickness of Ordered Mesoporous Graphene by Exploiting Ligand Exchange of Colloidal Nanocrystals

Science.gov (United States)

Han, Dandan; Yan, Yancui; Wei, Jishi; Wang, Biwei; Li, Tongtao; Guo, Guannan; Yang, Dong; Xie, Songhai; Dong, Angang

2017-12-01

Because of their unique physical properties, three-dimensional (3D) graphene has attracted enormous attention over the past years. However, it is still a challenge to precisely control the layer thickness of 3D graphene. Here, we report a novel strategy to rationally adjust the wall thickness of ordered mesoporous graphene (OMG). By taking advantage of ligand exchange capability of colloidal Fe3O4 nanocrystals, we are able to fine-tune the wall thickness of OMG from 2 to 6 layers of graphene by tailoring the hydrocarbon ligands attached to the nanocrystal surface. When evaluated as electrocatalyst for oxygen reduction reaction upon S and N doping, the 4-layer OMG is found to show better catalytic performance compared with its 2- and 6-layer counterparts, which we attribute to the enhanced exposure of active sites resulting from its ultrathin wall thickness and high surface area.

Glucagon-like peptide-1 receptor ligand interactions: structural cross talk between ligands and the extracellular domain.

Directory of Open Access Journals (Sweden)

Graham M West

Full Text Available Activation of the glucagon-like peptide-1 receptor (GLP-1R in pancreatic β-cells potentiates insulin production and is a current therapeutic target for the treatment of type 2 diabetes mellitus (T2DM. Like other class B G protein-coupled receptors (GPCRs, the GLP-1R contains an N-terminal extracellular ligand binding domain. N-terminal truncations on the peptide agonist generate antagonists capable of binding to the extracellular domain, but not capable of activating full length receptor. The main objective of this study was to use Hydrogen/deuterium exchange (HDX to identify how the amide hydrogen bonding network of peptide ligands and the extracellular domain of GLP-1R (nGLP-1R were altered by binding interactions and to then use this platform to validate direct binding events for putative GLP-1R small molecule ligands. The HDX studies presented here for two glucagon-like peptide-1 receptor (GLP-1R peptide ligands indicates that the antagonist exendin-4[9-39] is significantly destabilized in the presence of nonionic detergents as compared to the agonist exendin-4. Furthermore, HDX can detect stabilization of exendin-4 and exendin-4[9-39] hydrogen bonding networks at the N-terminal helix [Val19 to Lys27] upon binding to the N-terminal extracellular domain of GLP-1R (nGLP-1R. In addition we show hydrogen bonding network stabilization on nGLP-1R in response to ligand binding, and validate direct binding events with the extracellular domain of the receptor for putative GLP-1R small molecule ligands.

Mapping the surface of Escherichia coli peptide deformylase by NMR with organic solvents.

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Byerly, Douglas W; McElroy, Craig A; Foster, Mark P

2002-07-01

Identifying potential ligand binding sites on a protein surface is an important first step for targeted structure-based drug discovery. While performing control experiments with Escherichia coli peptide deformylase (PDF), we noted that the organic solvents used to solubilize some ligands perturbed many of the same resonances in PDF as the small molecule inhibitors. To further explore this observation, we recorded (15)N HSQC spectra of E. coli peptide deformylase (PDF) in the presence of trace quantities of several simple organic solvents (acetone, DMSO, ethanol, isopropanol) and identified their sites of interaction from local perturbation of amide chemical shifts. Analysis of the protein surface structure revealed that the ligand-induced shift perturbations map to the active site and one additional surface pocket. The correlation between sites of solvent and inhibitor binding highlights the utility of organic solvents to rapidly and effectively validate and characterize binding sites on proteins prior to designing a drug discovery screen. Further, the solvent-induced perturbations have implications for the use of organic solvents to dissolve candidate ligands in NMR-based screens.

EXAFS Studies of Some Copper(II) Mixed-Ligand Complexes

International Nuclear Information System (INIS)

Joshi, S. K.; Katare, R. K.; Shrivastava, B. D.

2007-01-01

X-ray K-absorption spectroscopic studies have been carried out on copper (II) mixed-ligand complexes with glutamic acid and aspartic acid as the primary ligands, where as water, pyridine, imidazole and benz-imidazole have been used as secondary ligands. Chemical shifts obtained from the X-ray absorption data have indicated that the glutamic acid complexes are more ionic as compared to their corresponding aspartic acid complexes having similar secondary ligands. Further, we have estimated the average metal-ligand bond distances from the from structure data. For the different complexes studied under the present investigation, the studies reveal that the bonding parameter α1 decreases with the increase in the percentage covalency of the metal-ligand bond. Thus, the bonding parameter α1 may be used for the estimation of percentage covalency of the metal-ligand bond in other similar complexes

Synthesis of Alkanethiolate-Capped Metal Nanoparticles Using Alkyl Thiosulfate Ligand Precursors: A Method to Generate Promising Reagents for Selective Catalysis

Directory of Open Access Journals (Sweden)

Khin Aye San

2018-05-01

Full Text Available Evaluation of metal nanoparticle catalysts functionalized with well-defined thiolate ligands can be potentially important because such systems can provide a spatial control in the reactivity and selectivity of catalysts. A synthetic method utilizing Bunte salts (sodium S-alkylthiosulfates allows the formation of metal nanoparticles (Au, Ag, Pd, Pt, and Ir capped with alkanethiolate ligands. The catalysis studies on Pd nanoparticles show a strong correlation between the surface ligand structure/composition and the catalytic activity and selectivity for the hydrogenation/isomerization of alkenes, dienes, trienes, and allylic alcohols. The high selectivity of Pd nanoparticles is driven by the controlled electronic properties of the Pd surface limiting the formation of Pd–alkene adducts (or intermediates necessary for (additional hydrogenation. The synthesis of water soluble Pd nanoparticles using ω-carboxylate-S-alkanethiosulfate salts is successfully achieved and these Pd nanoparticles are examined for the hydrogenation of various unsaturated compounds in both homogeneous and heterogeneous environments. Alkanethiolate-capped Pt nanoparticles are also successfully synthesized and further investigated for the hydrogenation of various alkynes to understand their geometric and electronic surface properties. The high catalytic activity of activated terminal alkynes, but the significantly low activity of internal alkynes and unactivated terminal alkynes, are observed for Pt nanoparticles.

Methods To Identify Aptamers against Cell Surface Biomarkers

Directory of Open Access Journals (Sweden)

Frédéric Ducongé

2011-09-01

Full Text Available Aptamers are nucleic acid-based ligands identified through a process of molecular evolution named SELEX (Systematic Evolution of Ligands by Exponential enrichment. During the last 10-15 years, numerous aptamers have been developed specifically against targets present on or associated with the surface of human cells or infectious pathogens such as viruses, bacteria, fungi or parasites. Several of the aptamers have been described as potent probes, rivalling antibodies, for use in flow cytometry or microscopy. Some have also been used as drugs by inhibiting or activating functions of their targets in a manner similar to neutralizing or agonistic antibodies. Additionally, it is straightforward to conjugate aptamers to other agents without losing their affinity and they have successfully been used in vitro and in vivo to deliver drugs, siRNA, nanoparticles or contrast agents to target cells. Hence, aptamers identified against cell surface biomarkers represent a promising class of ligands. This review presents the different strategies of SELEX that have been developed to identify aptamers for cell surface-associated proteins as well as some of the methods that are used to study their binding on living cells.

Interactions between alkaline earth cations and oxo ligands. DFT study of the affinity of the Mg²+ cation for phosphoryl ligands.

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da Costa, Leonardo Moreira; de Mesquita Carneiro, José Walkimar; Paes, Lilian Weitzel Coelho

2011-08-01

DFT (B3LYP/6-31+G(d)) calculations of Mg(2+) affinities for a set of phosphoryl ligands were performed. Two types of ligands were studied: a set of trivalent [O = P(R)] and a set of pentavalent phosphoryl ligands [O = P(R)(3)] (R = H, F, Cl, Br, OH, OCH(3), CH(3), CN, NH(2) and NO(2)), with R either bound directly to the phosphorus atom or to the para position of a phenyl ring. The affinity of the Mg(2+) cation for the ligands was quantified by means of the enthalpy for the substitution of one water molecule in the [Mg(H(2)O)(6)](2+) complex for a ligand. The enthalpy of substitution was correlated with electronic and geometric parameters. Electron-donor groups increase the interaction between the cation and the ligand, while electron-acceptor groups decrease the interaction enthalpy.

'Good Governance' dan 'Governability'

Directory of Open Access Journals (Sweden)

- Pratikno

2005-03-01

Full Text Available The article endeavors to trace the outset of governance concept, its dominant meanings and discourse, and its implication towards governability. The central role of government in the governing processes has predominantly been adopted. The concept of governance was emerged precisely in the context of the failure of government as key player in regulation, economic redistribution and political participation. Governance is therefore aimed to emphasize pattern of governing which are based both on democratic mechanism and sound development management. However, practices of such good governance concept –which are mainly adopted and promoted by donor states and agencies– tend to degrade state and/or government authority and legitimacy. Traditional function of the state as sole facilitator of equal societal, political and legal membership among citizens has been diminished. The logic of fair competition has been substituted almost completely by the logic of free competition in nearly all sectors of public life. The concept and practices of good governance have resulted in decayed state authority and failed state which in turn created a condition for "ungovernability". By promoting democratic and humane governance, the article accordingly encourages discourse to reinstall and bring the idea of accountable state back in.

Is governance, gross domestic product, inequality, population size or country surface area associated with coverage and equity of health interventions? Ecological analyses of cross-sectional surveys from 80 countries.

Science.gov (United States)

Wehrmeister, Fernando C; da Silva, Inácio Crochemore M; Barros, Aluisio J D; Victora, Cesar G

2017-01-01

To assess associations between national characteristics, including governance indicators, with a proxy for universal health coverage in reproductive, maternal, newborn and child health (RMNCH). Ecological analysis based on data from national standardised cross-sectional surveys. Low-income and middle-income countries with a Demographic and Health Survey or a Multiple Indicator Cluster Survey since 2005. 1 246 710 mothers and 2 129 212 children from 80 national surveys. Gross domestic product (GDP), country surface area, population, Gini index and six governance indicators (control of corruption, political stability and absence of violence, government effectiveness, regulatory quality, rule of law, and voice and accountability). Levels and inequality in the composite coverage index (CCI), a weighted average of eight RMNCH interventions. Relative and absolute inequalities were measured through the concentration index (CIX) and slope index of inequality (SII) for CCI, respectively. The average values of CCI (70.5% (SD=13.3)), CIX (5.3 (SD=5.1)) and mean slope index (19.8 (SD=14.7)) were calculated. In the unadjusted analysis, all governance variables and GDP were positively associated with the CCI and negatively with inequalities. Country surface showed inverse associations with both inequality indices. After adjustment, among the governance indicators, only political stability and absence of violence was directly related to CCI (β=6.3; 95% CI 3.6 to 9.1; p<0.001) and inversely associated with relative (CIX; β=-1.4; 95% CI -2.4 to -0.4; p=0.007) and absolute (SII; β=-5.3; 95% CI -8.9 to -1.7; p=0.005) inequalities. The strongest associations with governance indicators were found in the poorest wealth quintile. Similar patterns were observed for GDP. Country surface area was inversely related to inequalities on CCI. Levels and equity in RMNCH interventions are positively associated with political stability and absence of violence, and with GDP, and inversely

Electrostatically induced recruitment of membrane peptides into clusters requires ligand binding at both interfaces.

Directory of Open Access Journals (Sweden)

Yuri N Antonenko

Full Text Available Protein recruitment to specific membrane locations may be governed or facilitated by electrostatic attraction, which originates from a multivalent ligand. Here we explored the energetics of a model system in which this simple electrostatic recruitment mechanism failed. That is, basic poly-L-lysine binding to one leaflet of a planar lipid bilayer did not recruit the triply-charged peptide (O-Pyromellitylgramicidin. Clustering was only observed in cases where PLL was bound to both channel ends. Clustering was indicated (i by the decreased diffusional PLL mobility D(PLL and (ii by an increased lifetime τ(PLL of the clustered channels. In contrast, if PLL was bound to only one leaflet, neither D(PLL nor τ(P changed. Simple calculations suggest that electrostatic repulsion of the unbound ends prevented neighboring OPg dimers from approaching each other. We believe that a similar mechanism may also operate in cell signaling and that it may e.g. contribute to the controversial results obtained for the ligand driven dimerization of G protein-coupled receptors.

Semiconductor Quantum Dots with Photoresponsive Ligands.

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Sansalone, Lorenzo; Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Raymo, Françisco M; Garcia-Amorós, Jaume

2016-10-01

Photochromic or photocaged ligands can be anchored to the outer shell of semiconductor quantum dots in order to control the photophysical properties of these inorganic nanocrystals with optical stimulations. One of the two interconvertible states of the photoresponsive ligands can be designed to accept either an electron or energy from the excited quantum dots and quench their luminescence. Under these conditions, the reversible transformations of photochromic ligands or the irreversible cleavage of photocaged counterparts translates into the possibility to switch luminescence with external control. As an alternative to regulating the photophysics of a quantum dot via the photochemistry of its ligands, the photochemistry of the latter can be controlled by relying on the photophysics of the former. The transfer of excitation energy from a quantum dot to a photocaged ligand populates the excited state of the species adsorbed on the nanocrystal to induce a photochemical reaction. This mechanism, in conjunction with the large two-photon absorption cross section of quantum dots, can be exploited to release nitric oxide or to generate singlet oxygen under near-infrared irradiation. Thus, the combination of semiconductor quantum dots and photoresponsive ligands offers the opportunity to assemble nanostructured constructs with specific functions on the basis of electron or energy transfer processes. The photoswitchable luminescence and ability to photoinduce the release of reactive chemicals, associated with the resulting systems, can be particularly valuable in biomedical research and can, ultimately, lead to the realization of imaging probes for diagnostic applications as well as to therapeutic agents for the treatment of cancer.

Design of a multi-dopamine-modified polymer ligand optimally suited for interfacing magnetic nanoparticles with biological systems.

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Wang, Wentao; Ji, Xin; Na, Hyon Bin; Safi, Malak; Smith, Alexandra; Palui, Goutam; Perez, J Manuel; Mattoussi, Hedi

2014-06-03

We have designed a set of multifunctional and multicoordinating polymer ligands that are optimally suited for surface functionalizing iron oxide and potentially other magnetic nanoparticles (NPs) and promoting their integration into biological systems. The amphiphilic polymers are prepared by coupling (via nucleophilic addition) several amine-terminated dopamine anchoring groups, poly(ethylene glycol) moieties, and reactive groups onto a poly(isobutylene-alt-maleic anhydride) (PIMA) chain. This design greatly benefits from the highly efficient and reagent-free one-step reaction of maleic anhydride groups with amine-containing molecules. The availability of several dopamine groups in the same ligand greatly enhances the ligand affinity, via multiple coordination, to the magnetic NPs, while the hydrophilic and reactive groups promote colloidal stability in buffer media and allow subsequent conjugation with target biomolecules. Iron oxide nanoparticles ligand exchanged with these polymer ligands have a compact hydrodynamic size and exhibit enhanced long-term colloidal stability over the pH range of 4-12 and in the presence of excess electrolytes. Nanoparticles ligated with terminally reactive polymers have been easily coupled to target dyes and tested in live cell imaging with no measurable cytotoxicity. Finally, the resulting hydrophilic nanoparticles exhibit large and size-dependent r2 relaxivity values.

Discovering protein-ligand chalcogen bonding in the protein data bank using endocyclic sulfur-containing heterocycles as ligand search subsets.

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Mitchell, Miguel O

2017-09-24

The chalcogen bond, the noncovalent, electrostatic attraction between covalently bonded atoms in group 16 and Lewis bases, is present in protein-ligand interactions based on X-ray structures deposited in the Protein Data Bank (PDB). Discovering protein-ligand chalcogen bonding in the PDB employed a strategy that focused on searching the database for protein complexes of five-membered, heterocyclic ligands containing endocyclic sulfur with endo electron-withdrawing groups (isothiazoles; thiazoles; 1,2,3-, 1,2.4-, 1,2,5-, 1,3,4-thiadiazoles) and thiophenes with exo electron-withdrawing groups, e.g., 2-chloro, 2-bromo, 2-amino, 2-alkylthio. Out of 930 ligands investigated, 33 or 3.5% have protein-ligand S---O interactions of which 31 are chalcogen bonds and two appear to be S---HO hydrogen bonds. The bond angles for some of the chalcogen bonds found in the PDB are less than 90°, and an electrostatic model is proposed to explain this phenomenon.

Impacts of select organic ligands on the colloidal stability, dissolution dynamics, and toxicity of silver nanoparticles.

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Pokhrel, Lok R; Dubey, Brajesh; Scheuerman, Phillip R

2013-11-19

Key understanding of potential transformations that may occur on silver nanoparticle (AgNP) surface upon interaction with naturally ubiquitous organic ligands (e.g., -SH (thoil), humic acid, or -COO (carboxylate)) is limited. Herein we investigated how dissolved organic carbon (DOC), -SH (in cysteine, a well-known Ag(+) chelating agent), and -COO (in trolox, a well-known antioxidant) could alter the colloidal stability, dissolution rate, and toxicity of citrate-functionalized AgNPs (citrate-AgNPs) against a keystone crustacean Daphnia magna. Cysteine, DOC, or trolox amendment of citrate-AgNPs differentially modified particle size, surface properties (charge, plasmonic spectra), and ion release dynamics, thereby attenuating (with cysteine or trolox) or promoting (with DOC) AgNP toxicity. Except with DOC amendment, the combined toxicity of AgNPs and released Ag under cysteine or trolox amendment was lower than of AgNO3 alone. The results of this study show that citrate-AgNP toxicity can be associated with oxidative stress, ion release, and the organism biology. Our evidence suggests that specific organic ligands available in the receiving waters can differentially surface modify AgNPs and alter their environmental persistence (changing dissolution dynamics) and subsequently the toxicity; hence, we caveat to generalize that surface modified nanoparticles upon environmental release may not be toxic to receptor organisms.

Metal-Ligand Cooperative Reactivity in the (pseudo)-Dearomatized PNX(P) Systems: the Influence of the Zwitterionic Form in Dearomatized Pincer Complexes

KAUST Repository

Goncalves, Theo

2017-09-01

The concept of aromaticity in pincer ligands and complexes was discussed in order to provide insights into their metal-ligand cooperative activities. The aromatic PNx(P) and dearomatized PNx(P)* pincer ligands and the corresponding transition metal complexes were studied with the nucleus-independent chemical shift (NICSzz), anisotropy of the current (induced) density (ACID), isochemical shielding surfaces (ICSSzz), harmonic oscillator model of aromaticity (HOMA), MCBO, Shannon aromaticity, and natural bond order (NBO) analyses. The study on the model systems showed that for the dearomatized species the decrease of the NICS(1)zz value comes with the larger contribution of the aromatic zwitterionic mesomeric form. In all examples, the incorporation of the metal center into the pincer ligand decreases the NICS(1)zz values. The DFT calculations support the dearomatized pyridine ring in PNP* or PNN* ligand indeed being nonaromatic, in contrast to the PN3(P)* ligand which has partial aromatic character due to the larger contribution of the zwitterionic resonance structure. The difference in aromaticity between the rings contributes to the thermodynamic balance of the metal ligand cooperative reactions, changing the energetics of the process when different dearomatized pincer ligands are used. This was further exemplified by aromaticity analysis of the heterolytic hydrogen cleavage reaction of ruthenium PNN complexes of Milstein and the PN3 of Huang, with similar geometries but distinctive thermodynamic preference.

Metal-Ligand Cooperative Reactivity in the (pseudo)-Dearomatized PNX(P) Systems: the Influence of the Zwitterionic Form in Dearomatized Pincer Complexes

KAUST Repository

Goncalves, Theo; Huang, Kuo-Wei

2017-01-01

The concept of aromaticity in pincer ligands and complexes was discussed in order to provide insights into their metal-ligand cooperative activities. The aromatic PNx(P) and dearomatized PNx(P)* pincer ligands and the corresponding transition metal complexes were studied with the nucleus-independent chemical shift (NICSzz), anisotropy of the current (induced) density (ACID), isochemical shielding surfaces (ICSSzz), harmonic oscillator model of aromaticity (HOMA), MCBO, Shannon aromaticity, and natural bond order (NBO) analyses. The study on the model systems showed that for the dearomatized species the decrease of the NICS(1)zz value comes with the larger contribution of the aromatic zwitterionic mesomeric form. In all examples, the incorporation of the metal center into the pincer ligand decreases the NICS(1)zz values. The DFT calculations support the dearomatized pyridine ring in PNP* or PNN* ligand indeed being nonaromatic, in contrast to the PN3(P)* ligand which has partial aromatic character due to the larger contribution of the zwitterionic resonance structure. The difference in aromaticity between the rings contributes to the thermodynamic balance of the metal ligand cooperative reactions, changing the energetics of the process when different dearomatized pincer ligands are used. This was further exemplified by aromaticity analysis of the heterolytic hydrogen cleavage reaction of ruthenium PNN complexes of Milstein and the PN3 of Huang, with similar geometries but distinctive thermodynamic preference.

Precipitation kinetics of Mg-carbonates, influence of organic ligands and consequences for CO2 mineral sequestration

International Nuclear Information System (INIS)

Gautier, Q.

2012-01-01

Forming magnesium carbonate minerals through carbonation of magnesium silicates has been proposed as a safe and durable way to store carbon dioxide, with a possibly high potential to offset anthropogenic CO 2 emissions. To date however, chemical reactions involved in this process are facing strong kinetic limitations, which originate in the low reactivity of both Mg-silicates and Mg-carbonates. Numerous studies have focused on the dissolution of Mg-silicates, under the questionable hypothesis that this step limits the whole process. This thesis work focuses instead on the mechanisms and rates of formation of magnesium carbonates, which are the final products of carbonation reactions. The first part of the work is dedicated to studying the influence on magnesite precipitation kinetics of three organic ligands known to accelerate Mg-silicates dissolution rates: oxalate, citrate and EDTA. With help of mixed-flow reactor experiments performed between 100 and 150 C, we show that these ligands significantly reduce magnesite growth rates, through two combined mechanisms: (1) complexation of Mg 2+ cations in aqueous solution, which was rigorously estimated from a thermodynamic database established through a critical review of the literature, and (2) adsorption of ligands to a limited number of surface sites, leading to a decrease of the precipitation rate constant. The observed growth inhibition is maximal with citrate. We then used hydrothermal atomic force microscopy to probe the origin of the documented growth inhibition. Our observations show that citrate and oxalate interact with the crystal growth process on magnesite surface, modifying the shape of growth hillocks as well as the step generation frequency through spiral growth. We also show that the ligands adsorb preferentially on different kink-sites, which is probably related to their different structures and chemical properties. We propose that the stronger magnesite growth inhibition caused by citrate is related

Dextran as a Generally Applicable Multivalent Scaffold for Improving Immunoglobulin-Binding Affinities of Peptide and Peptidomimetic Ligands

Science.gov (United States)

2015-01-01

Molecules able to bind the antigen-binding sites of antibodies are of interest in medicine and immunology. Since most antibodies are bivalent, higher affinity recognition can be achieved through avidity effects in which a construct containing two or more copies of the ligand engages both arms of the immunoglobulin simultaneously. This can be achieved routinely by immobilizing antibody ligands at high density on solid surfaces, such as ELISA plates, but there is surprisingly little literature on scaffolds that routinely support bivalent binding of antibody ligands in solution, particularly for the important case of human IgG antibodies. Here we show that the simple strategy of linking two antigens with a polyethylene glycol (PEG) spacer long enough to span the two arms of an antibody results in higher affinity binding in some, but not all, cases. However, we found that the creation of multimeric constructs in which several antibody ligands are displayed on a dextran polymer reliably provides much higher affinity binding than is observed with the monomer in all cases tested. Since these dextran conjugates are simple to construct, they provide a general and convenient strategy to transform modest affinity antibody ligands into high affinity probes. An additional advantage is that the antibody ligands occupy only a small number of the reactive sites on the dextran, so that molecular cargo can be attached easily, creating molecules capable of delivering this cargo to cells displaying antigen-specific receptors. PMID:25073654

A tandem regression-outlier analysis of a ligand cellular system for key structural modifications around ligand binding.

Science.gov (United States)

Lin, Ying-Ting

2013-04-30

A tandem technique of hard equipment is often used for the chemical analysis of a single cell to first isolate and then detect the wanted identities. The first part is the separation of wanted chemicals from the bulk of a cell; the second part is the actual detection of the important identities. To identify the key structural modifications around ligand binding, the present study aims to develop a counterpart of tandem technique for cheminformatics. A statistical regression and its outliers act as a computational technique for separation. A PPARγ (peroxisome proliferator-activated receptor gamma) agonist cellular system was subjected to such an investigation. Results show that this tandem regression-outlier analysis, or the prioritization of the context equations tagged with features of the outliers, is an effective regression technique of cheminformatics to detect key structural modifications, as well as their tendency of impact to ligand binding. The key structural modifications around ligand binding are effectively extracted or characterized out of cellular reactions. This is because molecular binding is the paramount factor in such ligand cellular system and key structural modifications around ligand binding are expected to create outliers. Therefore, such outliers can be captured by this tandem regression-outlier analysis.

Synthesis and labelling of Df-DUPA-Pep with gallium-68 and zirconium-89 as new PSMA ligands

International Nuclear Information System (INIS)

Benjamin Baur; Ehab Al-Momani; Noeen Malik; Hans-Juergen Machulla; Reske, S.N.; Christoph Solbach; Elena Andreolli; University of Milano-Bicocca, Milan

2014-01-01

Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer. Due to the specificity of expression of PSMA, numerous urea-based ligands have been synthesized until now. In the current study, we describe the coupling of the chelator desferrioxamine to DUPA-Pep and the subsequent labelling with Ga-68 and Zr-89 as new PSMA ligands. The labelling step is performed at room temperature and pH 7.5. In both radiosyntheses, the RCYs were higher than 95 % within 10 min, making dispensable any further purification and providing the radiotracers directly applicable for further utilization. (author)

New Ru(II) complexes for dual photoreactivity: ligand exchange and (1)O2 generation.

Science.gov (United States)

Knoll, Jessica D; Albani, Bryan A; Turro, Claudia

2015-08-18

Uncovering the factors that govern the electronic structure of Ru(II)-polypyridyl complexes is critical in designing new compounds for desired photochemical reactions, and strategies to tune excited states for ligand dissociation and (1)O2 production are discussed herein. The generally accepted mechanism for photoinduced ligand dissociation proposes that population of the dissociative triplet ligand field ((3)LF) state proceeds through thermal population from the vibrationally cooled triplet metal-to-ligand charge transfer ((3)MLCT) state; however, temperature-dependent emission spectroscopy provides varied activation energies using the emission and ligand exchange quantum yields for [Ru(bpy)2(L)2](2+) (bpy = 2,2'-bipyridine; L = CH3CN or py). This suggests that population of the (3)LF state proceeds from the vibrationally excited (3)MLCT state. Because the quantum yield of ligand dissociation for nitriles is much more efficient than that for py, steric bulk was introduced into the ligand set to distort the pseudo-octahedral geometry and lower the energy of the (3)LF state. The py dissociation quantum yield with 500 nm irradiation in a series of [Ru(tpy)(NN)(py)](2+) complexes (tpy = 2,2':6',2″-terpyridine; NN = bpy, 6,6'-dimethyl-2,2'-bipyridine (Me2bpy), 2,2'-biquinoline (biq)) increases by 2-3 orders of magnitude with the sterically bulky Me2bpy and biq ligands relative to bpy. Ultrafast transient absorption spectroscopy reveals population of the (3)LF state within 3-7 ps when NN is bulky, and density functional theory calculations support stabilized (3)LF states. Dual activity via ligand dissociation and (1)O2 production can be achieved by careful selection of the ligand set to tune the excited-state dynamics. Incorporation of an extended π system in Ru(II) complexes such as [Ru(bpy)(dppn)(CH3CN)2](2+) (dppn = benzo[i]dipyrido[3,2-a:2',3'-c]phenazine) and [Ru(tpy)(Me2dppn)(py)](2+) (Me2dppn = 3,6-dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine) introduces

New Ru(II) Complexes for Dual Photoreactivity: Ligand Exchange and 1O2 Generation

Science.gov (United States)

Knoll, Jessica D.; Albani, Bryan A.; Turro, Claudia

2016-01-01

CONSPECTUS Uncovering the factors that govern the electronic structure of Ru(II)–polypyridyl complexes is critical in designing new compounds for desired photochemical reactions, and strategies to tune excited states for ligand dissociation and 1O2 production are discussed herein. The generally accepted mechanism for photoinduced ligand dissociation proposes that population of the dissociative triplet ligand field (3LF) state proceeds through thermal population from the vibrationally cooled triplet metal-to-ligand charge transfer (3MLCT) state; however, temperature-dependent emission spectroscopy provides varied activation energies using the emission and ligand exchange quantum yields for [Ru(bpy)2(L)2]2+ (bpy = 2,2′-bipyridine; L = CH3CN or py). This suggests that population of the 3LF state proceeds from the vibrationally excited 3MLCT state. Because the quantum yield of ligand dissociation for nitriles is much more efficient than that for py, steric bulk was introduced into the ligand set to distort the pseudo-octahedral geometry and lower the energy of the 3LF state. The py dissociation quantum yield with 500 nm irradiation in a series of [Ru(tpy)(NN)(py)]2+ complexes (tpy = 2,2′:6′,2″-terpyridine; NN = bpy, 6,6′-dimethyl-2,2′-bipyridine (Me2bpy), 2,2′-biquinoline (biq)) increases by 2–3 orders of magnitude with the sterically bulky Me2bpy and biq ligands relative to bpy. Ultrafast transient absorption spectroscopy reveals population of the 3LF state within 3–7 ps when NN is bulky, and density functional theory calculations support stabilized 3LF states. Dual activity via ligand dissociation and 1O2 production can be achieved by careful selection of the ligand set to tune the excited-state dynamics. Incorporation of an extended π system in Ru(II) complexes such as [Ru(bpy)(dppn)(CH3CN)2]2+ (dppn = benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(tpy)(Me2dppn)(py)]2+ (Me2dppn = 3,6-dimethylbenzo[i]dipyrido[3,2-a:2′,3�

Development and evaluation of targeting ligands surface modified paclitaxel nanocrystals

Energy Technology Data Exchange (ETDEWEB)

Sohn, Jeong Sun [Division of Undeclared Majors, Chosun University, Gwangju 501-759 (Korea, Republic of); Yoon, Doo-Soo; Sohn, Jun Youn [Department of Bioenvironmental & Chemical Engineering, Chosun College of Science & Technology, Gwangju 501-744 (Korea, Republic of); Park, Jeong-Sook, E-mail: eicosa@cnu.ac.kr [College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Choi, Jin-Seok, E-mail: c34281@gmail.com [College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of)

2017-03-01

To overcome the toxicity of excipient or blank nanoparticles for drug delivery nano-system, the surface modified paclitaxel nanocrystals (PTX-NC) have been developed. PTX-NCs were prepared by nano-precipitation method. The surface of PTX-NCs were modified by grafting with apo-transferrin (Tf) or hyaluronic acid (HA). The physical properties of PTX-NCs were evaluated by field emission scanning electron microscope (FE-SEM), zeta-sizer, zeta-potential, differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectrometry. In vitro drug release study was performed in phosphate buffered saline (PBS) with or without 0.5% (w/v) Tween 80 for 24 h. Cellular uptake was studied at time intervals of 0.5, 1, and 2 h in MCF-7 cells, and cell growth inhibition study was performed for 24 h using MCF-7 cells (cancer cells), and HaCaT cells (normal cells). Three different types of PTX-NCs with a mean size of 236.0 ± 100.6 nm (PTX-NC), 302.0 ± 152.0 nm (Tf-PTX-NC) and 339 ± 180.6 nm (HA-PTX-NC) were successfully prepared. The drug release profiles showed 29.1%/6.9% (PTX (pure)), 40.7%/23.9% (PTX-NC), 50.5%/25.1% (Tf-PTX-NC) and 46.8/24.8% (HA-PTX-NC) in PBS with/without 0.5% (w/v) Tween 80 for 24 h, respectively. As per the results, the drug release of PTX-NCs showed the faster release as compared to that of PTX (pure). Surface modified PTX-NCs exhibited higher values for cell permeability than unmodified PTX-NC in the cellular uptake study. Surface modified PTX-NCs inhibited the cell growth approximately to 60% in MCF-7 cells, however effect of surface modified PTX-NCs on normal cell line was lower than the PTX-NC and PTX (pure). In conclusion, biological macromolecules (Tf or HA) surface modified PTX-NC enhanced the cellular uptake and the cell growth inhibition. - Highlights: • Surface modified PTX-NCs with HA and Tf are successfully prepared by adsorption method. • Enhanced cellular uptake of modified PTX-NCs compared to unmodified PTX-NC • Improved

Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor.

Science.gov (United States)

Yin, Donghua; He, Yali; Perera, Minoli A; Hong, Seoung Soo; Marhefka, Craig; Stourman, Nina; Kirkovsky, Leonid; Miller, Duane D; Dalton, James T

2003-01-01

The purposes of the present studies were to examine the androgen receptor (AR) binding ability and in vitro functional activity of multiple series of nonsteroidal compounds derived from known antiandrogen pharmacophores and to investigate the structure-activity relationships (SARs) of these nonsteroidal compounds. The AR binding properties of sixty-five nonsteroidal compounds were assessed by a radioligand competitive binding assay with the use of cytosolic AR prepared from rat prostates. The AR agonist and antagonist activities of high-affinity ligands were determined by the ability of the ligand to regulate AR-mediated transcriptional activation in cultured CV-1 cells, using a cotransfection assay. Nonsteroidal compounds with diverse structural features demonstrated a wide range of binding affinity for the AR. Ten compounds, mainly from the bicalutamide-related series, showed a binding affinity superior to the structural pharmacophore from which they were derived. Several SARs regarding nonsteroidal AR binding were revealed from the binding data, including stereoisomeric conformation, steric effect, and electronic effect. The functional activity of high-affinity ligands ranged from antagonist to full agonist for the AR. Several structural features were found to be determinative of agonist and antagonist activities. The nonsteroidal AR agonists identified from the present studies provided a pool of candidates for further development of selective androgen receptor modulators (SARMs) for androgen therapy. Also, these studies uncovered or confirmed numerous important SARs governing AR binding and functional properties by nonsteroidal molecules, which would be valuable in the future structural optimization of SARMs.

Elimination of a ligand gating site generates a supersensitive olfactory receptor.

Science.gov (United States)

Sharma, Kanika; Ahuja, Gaurav; Hussain, Ashiq; Balfanz, Sabine; Baumann, Arnd; Korsching, Sigrun I

2016-06-21

Olfaction poses one of the most complex ligand-receptor matching problems in biology due to the unparalleled multitude of odor molecules facing a large number of cognate olfactory receptors. We have recently deorphanized an olfactory receptor, TAAR13c, as a specific receptor for the death-associated odor cadaverine. Here we have modeled the cadaverine/TAAR13c interaction, exchanged predicted binding residues by site-directed mutagenesis, and measured the activity of the mutant receptors. Unexpectedly we observed a binding site for cadaverine at the external surface of the receptor, in addition to an internal binding site, whose mutation resulted in complete loss of activity. In stark contrast, elimination of the external binding site generated supersensitive receptors. Modeling suggests this site to act as a gate, limiting access of the ligand to the internal binding site and thereby downregulating the affinity of the native receptor. This constitutes a novel mechanism to fine-tune physiological sensitivity to socially relevant odors.

-Pincer Ligand Family through Ligand Post-Modification

KAUST Repository

Huang, Mei-Hui; Hu, Jinsong; Huang, Kuo-Wei

2017-01-01

A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

-Pincer Ligand Family through Ligand Post-Modification

KAUST Repository

Huang, Mei-Hui

2017-10-02

A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

Database of ligand-induced domain movements in enzymes

Directory of Open Access Journals (Sweden)

Hayward Steven

2009-03-01

Full Text Available Abstract Background Conformational change induced by the binding of a substrate or coenzyme is a poorly understood stage in the process of enzyme catalysed reactions. For enzymes that exhibit a domain movement, the conformational change can be clearly characterized and therefore the opportunity exists to gain an understanding of the mechanisms involved. The development of the non-redundant database of protein domain movements contains examples of ligand-induced domain movements in enzymes, but this valuable data has remained unexploited. Description The domain movements in the non-redundant database of protein domain movements are those found by applying the DynDom program to pairs of crystallographic structures contained in Protein Data Bank files. For each pair of structures cross-checking ligands in their Protein Data Bank files with the KEGG-LIGAND database and using methods that search for ligands that contact the enzyme in one conformation but not the other, the non-redundant database of protein domain movements was refined down to a set of 203 enzymes where a domain movement is apparently triggered by the binding of a functional ligand. For these cases, ligand binding information, including hydrogen bonds and salt-bridges between the ligand and specific residues on the enzyme is presented in the context of dynamical information such as the regions that form the dynamic domains, the hinge bending residues, and the hinge axes. Conclusion The presentation at a single website of data on interactions between a ligand and specific residues on the enzyme alongside data on the movement that these interactions induce, should lead to new insights into the mechanisms of these enzymes in particular, and help in trying to understand the general process of ligand-induced domain closure in enzymes. The website can be found at: http://www.cmp.uea.ac.uk/dyndom/enzymeList.do

Receptor-ligand binding sites and virtual screening.

Science.gov (United States)

Hattotuwagama, Channa K; Davies, Matthew N; Flower, Darren R

2006-01-01

Within the pharmaceutical industry, the ultimate source of continuing profitability is the unremitting process of drug discovery. To be profitable, drugs must be marketable: legally novel, safe and relatively free of side effects, efficacious, and ideally inexpensive to produce. While drug discovery was once typified by a haphazard and empirical process, it is now increasingly driven by both knowledge of the receptor-mediated basis of disease and how drug molecules interact with receptors and the wider physiome. Medicinal chemistry postulates that to understand a congeneric ligand series, or set thereof, is to understand the nature and requirements of a ligand binding site. Likewise, structural molecular biology posits that to understand a binding site is to understand the nature of ligands bound therein. Reality sits somewhere between these extremes, yet subsumes them both. Complementary to rules of ligand design, arising through decades of medicinal chemistry, structural biology and computational chemistry are able to elucidate the nature of binding site-ligand interactions, facilitating, at both pragmatic and conceptual levels, the drug discovery process.

Influence of chelating ligands on arsenic uptake by hydroponically grown rice seedlings (Oryza sativa L.): a preliminary study

Energy Technology Data Exchange (ETDEWEB)

Rahman, Mohammad A.; Hasegawa, Hiroshi; Ueda, Kazumasa; Maki, Teruya [Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa (Japan); Rahman, M.M. [Department of Botany, Faculty of Biological Sciences, Jahangirnagar University, Savar, Dhaka (Bangladesh)

2008-06-15

Ferric (oxyhydro-)oxides (FeO{sub x}) precipitate in the rhizosphere at neutral or alkaline pH and are adsorbed on the plant root surfaces. Consequently, the higher binding affinity of arsenate to FeO{sub x} and the low iron phytoavailability of the precipitated FeO{sub x} make the phytoremediation of arsenic difficult. In the present study, the influence of chelating ligands on arsenic and iron uptake by hydroponically grown rice seedlings (Oryza sativa L.) was investigated. When chelating ligands were not treated to the growth medium, about 63 and 71% of the total arsenic and iron were distributed in the root extract (outer root surfaces) of rice, respectively. On the other hand, ethylenediaminetetraacetic acid (EDTA), ethylenediaminedisuccinic acid (EDDS) and hydroxyiminodisuccinic acid (HIDS) desorbed a significant amount of arsenic from FeO{sub x} of the outer root surfaces. Therefore, the uptake of arsenic and iron into the roots and their subsequent translocation to the shoots of the rice seedlings increased significantly. The order of increasing arsenic uptake by chelating ligands was HIDS > EDTA > EDDS. Methylglycinediacetic acid (MGDA) and iminodisuccinic acid (IDS) might not be effective in arsenic solubilization from FeO{sub x}. The results suggest that EDDS and HIDS would be a good and environmentally safe choice to accelerate arsenic phytoavailability in the phytoremediation process because of their biodegradability and would be a competent alternative to the widely used non-biodegradable and environmentally persistent EDTA. (Abstract Copyright [2008], Wiley Periodicals, Inc.)

The affinity plutonium(IV) for nitrogen donor ligands

International Nuclear Information System (INIS)

Jarvis, N.V.; Hancock, R.D.

1994-01-01

Established ligand design principles are used to predict the solution chemistry of Pu(IV) with nitrogen donor ligands which do not contain carboxylate donors. pK a 's of the nitrogen donors are lowered by addition of hydroxyalkyl groups causing Pu(IV) to have a greater affinity for these ligands than for hydroxide. Potentiometric studies using the ligands N,N,N'N',N''-pentakis(2-hydroxypropyl)-1,4,7-triazaheptane; N,N,N',N',N''-pentakis(2-hydroxyethyl)-1,4,7-triazaheptane; N,N,N',N',N'-tetrakis(2-hydroxyethyl)-1,2-diaminoethane; N,N,N',N'-tetrakis(2-hydroxyethyl)-trans-1,2-diaminocyclohexane; 1,4,8,11-tetrakis(2-hydroxyethyl)-1,4,8,11-tetraazacyclotetradecane and N,N-bis(2-hydroxyethyl)glycine with Pu(IV) showed that Pu(IV) has a considerable aqueous solution chemistry with these ligands. Data were processed by the ESTA library of programs and stability constants for all the systems are reported. Implications for selective ligand design for Pu(IV) are discussed. (orig.)

Mixed ligand chelates of rare earths in aqueous solution

International Nuclear Information System (INIS)

Lakhani, S.U.; Thakur, G.S.; Sangal, S.P.

1981-01-01

Mixed ligand chelates of the 1:1 trivalent lanthanoids-EDTA, HEDTA and NTA chelates-1, 2-Dihydroxybenzene (Pyrocatechol) have been investigated at 35degC and 0.2 M ionic strength maintained by NaC10 4 . The formation of mixed ligand chelates has been found in all cases. The formation of mixed ligand chelates with EDTA shows the coordination number of lanthanoids to be eight, while the mixed ligand chelates with HEDTA and NTA shows the coordination number to be seven and six respectively. The stability constants of mixed ligand chelates are smaller than the binary complexes. The order of stability constants with respect to primary ligands follows the order NTA>HEDTA>EDTA. With respect to metal ions the stability constants increases with the decrease in ionic radii such as Gd< Er< Yb. (author)

A theoretical investigation on the neutral Cu(I) phosphorescent complexes with azole-based and phosphine mixed ligand

Science.gov (United States)

Ding, Xiao-Li; Shen, Lu; Zou, Lu-Yi; Ma, Ming-Shuo; Ren, Ai-Min

2018-04-01

A theoretical study on a series of neutral heteroleptic Cu(I) complexes with different azole-pyridine-based N^N ligands has been presented to get insight into the effect of various nitrogen atoms in the azole ring on photophysical properties. The results reveal that the highest occupied molecular orbital (HOMO) levels and the emission wavelengths of these complexes are mainly governed by the nitrogen atom number in azole ring. With the increasing number of nitrogen atom , the electron density distribution of HOMO gradually extend from the N^N ligand to the whole molecule, meanwhile, the improved contribution from Cu(d) orbits in HOMO results in an effective mixing of various charge transfermodes, and hence, the fast radiative decay(kr) and the slow non-radiative decay rate(knr) are achieved. The photoluminescence quantum yield (PLQY) show an apparent dependence on the nitrogen atom number in the five-membered nitrogen heterocycles. However, the increasing number of nitrogen atoms is not necessary for increasing PLQY. The complex 3 with 1,2,4-triazole-pyridine-based N^N ligands is considered to be a potential emitter with high phosphorescence efficiency. Finally, we hope that our investigations will contribute to systematical understanding and guiding for material molecular engineering.

Calculating the mean time to capture for tethered ligands and its effect on the chemical equilibrium of bound ligand pairs.

Science.gov (United States)

Shen, Lu; Decker, Caitlin G; Maynard, Heather D; Levine, Alex J

2016-09-01

We present here the calculation of the mean time to capture of a tethered ligand to the receptor. This calculation is then used to determine the shift in the partitioning between (1) free, (2) singly bound, and (3) doubly bound ligands in chemical equilibrium as a function of the length of the tether. These calculations are used in the research article Fibroblast Growth Factor 2 Dimer with Superagonist in vitro Activity Improves Granulation Tissue Formation During Wound Healing (Decker et al., in press [1]) to explain quantitatively how changes in polymeric linker length in the ligand dimers modifies the efficacy of these molecules relative to that of free ligands.

Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity.

Science.gov (United States)

Labani-Motlagh, Alireza; Israelsson, Pernilla; Ottander, Ulrika; Lundin, Eva; Nagaev, Ivan; Nagaeva, Olga; Dehlin, Eva; Baranov, Vladimir; Mincheva-Nilsson, Lucia

2016-04-01

Cancers constitutively produce and secrete into the blood and other biofluids 30-150 nm-sized endosomal vehicles called exosomes. Cancer-derived exosomes exhibit powerful influence on a variety of biological mechanisms to the benefit of the tumors that produce them. We studied the immunosuppressive ability of epithelial ovarian cancer (EOC) exosomes on two cytotoxic pathways of importance for anticancer immunity-the NKG2D receptor-ligand pathway and the DNAM-1-PVR/nectin-2 pathway. Using exosomes, isolated from EOC tumor explant and EOC cell-line culture supernatants, and ascitic fluid from EOC patients, we studied the expression of NKG2D and DNAM-1 ligands on EOC exosomes and their ability to downregulate the cognate receptors. Our results show that EOC exosomes differentially and constitutively express NKG2D ligands from both MICA/B and ULBP families on their surface, while DNAM-1 ligands are more seldom expressed and not associated with the exosomal membrane surface. Consequently, the NKG2D ligand-bearing EOC exosomes significantly downregulated the NKG2D receptor expression on peripheral blood mononuclear cells (PBMC) while the DNAM-1 receptor was unaffected. The downregulation of NKG2D receptor expression was coupled to inhibition of NKG2D receptor-ligand-mediated degranulation and cytotoxicity measured in vitro with OVCAR-3 and K562 cells as targets. The EOC exosomes acted as a decoy impairing the NKG2D mediated cytotoxicity while the DNAM-1 receptor-ligand system remained unchanged. Taken together, our results support and explain the mechanism behind the recently reported finding that in EOC, NK-cell recognition and killing of tumor cells was mainly dependent on DNAM-1 signaling while the contribution of the NKG2D receptor-ligand pathway was complementary and uncertain.

Importance of the pharmacological profile of the bound ligand in enrichment on nuclear receptors: toward the use of experimentally validated decoy ligands.

Science.gov (United States)

Lagarde, Nathalie; Zagury, Jean-François; Montes, Matthieu

2014-10-27

The evaluation of virtual ligand screening methods is of major importance to ensure their reliability. Taking into account the agonist/antagonist pharmacological profile should improve the quality of the benchmarking data sets since ligand binding can induce conformational changes in the nuclear receptor structure and such changes may vary according to the agonist/antagonist ligand profile. We indeed found that splitting the agonist and antagonist ligands into two separate data sets for a given nuclear receptor target significantly enhances the quality of the evaluation. The pharmacological profile of the ligand bound in the binding site of the target structure was also found to be an additional critical parameter. We also illustrate that active compound data sets for a given pharmacological activity can be used as a set of experimentally validated decoy ligands for another pharmacological activity to ensure a reliable and challenging evaluation of virtual screening methods.

The cell surface expressed nucleolin is a glycoprotein that triggers calcium entry into mammalian cells

International Nuclear Information System (INIS)

Losfeld, Marie-Estelle; Khoury, Diala El; Mariot, Pascal; Carpentier, Mathieu; Krust, Bernard; Briand, Jean-Paul; Mazurier, Joel; Hovanessian, Ara G.; Legrand, Dominique

2009-01-01

Nucleolin is an ubiquitous nucleolar phosphoprotein involved in fundamental aspects of transcription regulation, cell proliferation and growth. It has also been described as a shuttling molecule between nucleus, cytosol and the cell surface. Several studies have demonstrated that surface nucleolin serves as a receptor for various extracellular ligands implicated in cell proliferation, differentiation, adhesion, mitogenesis and angiogenesis. Previously, we reported that nucleolin in the extranuclear cell compartment is a glycoprotein containing N- and O-glycans. In the present study, we show that glycosylation is an essential requirement for surface nucleolin expression, since it is prevented when cells are cultured in the presence of tunicamycin, an inhibitor of N-glycosylation. Accordingly, surface but not nuclear nucleolin is radioactively labeled upon metabolic labeling of cells with [ 3 H]glucosamine. Besides its well-demonstrated role in the internalization of specific ligands, here we show that ligand binding to surface nucleolin could also induce Ca 2+ entry into cells. Indeed, by flow cytometry, microscopy and patch-clamp experiments, we show that the HB-19 pseudopeptide, which binds specifically surface nucleolin, triggers rapid and intense membrane Ca 2+ fluxes in various types of cells. The use of several drugs then indicated that Store-Operated Ca 2+ Entry (SOCE)-like channels are involved in the generation of these fluxes. Taken together, our findings suggest that binding of an extracellular ligand to surface nucleolin could be involved in the activation of signaling pathways by promoting Ca 2+ entry into cells

Targeting nanoparticles to M cells with non-peptidic ligands for oral vaccination.

Science.gov (United States)

Fievez, Virginie; Plapied, Laurence; des Rieux, Anne; Pourcelle, Vincent; Freichels, Hélène; Wascotte, Valentine; Vanderhaeghen, Marie-Lyse; Jerôme, Christine; Vanderplasschen, Alain; Marchand-Brynaert, Jacqueline; Schneider, Yves-Jacques; Préat, Véronique

2009-09-01

The presence of RGD on nanoparticles allows the targeting of beta1 integrins at the apical surface of human M cells and the enhancement of an immune response after oral immunization. To check the hypothesis that non-peptidic ligands targeting intestinal M cells or APCs would be more efficient for oral immunization than RGD, novel non-peptidic and peptidic analogs (RGD peptidomimitic (RGDp), LDV derivative (LDVd) and LDV peptidomimetic (LDVp)) as well as mannose were grafted on the PEG chain of PCL-PEG and incorporated in PLGA-based nanoparticles. RGD and RGDp significantly increased the transport of nanoparticles across an in vitro model of human M cells as compared to enterocytes. RGD, LDVp, LDVd and mannose enhanced nanoparticle uptake by macrophages in vitro. The intraduodenal immunization with RGDp-, LDVd- or mannose-labeled nanoparticles elicited a higher production of IgG antibodies than the intramuscular injection of free ovalbumin or intraduodenal administration of either non-targeted or RGD-nanoparticles. Targeted formulations were also able to induce a cellular immune response. In conclusion, the in vitro transport of nanoparticles, uptake by macrophages and the immune response were positively influenced by the presence of ligands at the surface of nanoparticles. These targeted-nanoparticles could thus represent a promising delivery system for oral immunization.

Expression of nociceptive ligands in canine osteosarcoma.

Science.gov (United States)

Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

2015-01-01

Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

Natural HLA-B*2705 Protein Ligands with Glutamine as Anchor Motif

Science.gov (United States)

Infantes, Susana; Lorente, Elena; Barnea, Eilon; Beer, Ilan; Barriga, Alejandro; Lasala, Fátima; Jiménez, Mercedes; Admon, Arie; López, Daniel

2013-01-01

The presentation of short viral peptide antigens by human leukocyte antigen (HLA) class I molecules on cell surfaces is a key step in the activation of cytotoxic T lymphocytes, which mediate the killing of pathogen-infected cells or initiate autoimmune tissue damage. HLA-B27 is a well known class I molecule that is used to study both facets of the cellular immune response. Using mass spectrometry analysis of complex HLA-bound peptide pools isolated from large amounts of HLA-B*2705+ cells, we identified 200 naturally processed HLA-B*2705 ligands. Our analyses revealed that a change in the position (P) 2 anchor motif was detected in the 3% of HLA-B*2705 ligands identified. B*2705 class I molecules were able to bind these six GlnP2 peptides, which showed significant homology to pathogenic bacterial sequences, with a broad range of affinities. One of these ligands was able to bind with distinct conformations to HLA-B27 subtypes differentially associated with ankylosing spondylitis. These conformational differences could be sufficient to initiate autoimmune damage in patients with ankylosing spondylitis-associated subtypes. Therefore, these kinds of peptides (short, with GlnP2, and similar low affinity to all HLA-B27 subtypes tested but with unlike conformations in differentially ankylosing spondylitis-associated subtypes) must not be excluded from future researches involving potential arthritogenic peptides. PMID:23430249

A Versatile Dinucleating Ligand Containing Sulfonamide Groups

DEFF Research Database (Denmark)

Sundberg, Jonas; Witt, Hannes; Cameron, Lisa

2014-01-01

ligand can be prepared in aqueous solutions using only divalent metal ions. Two of the copper(II) complexes, [Cu2(psmp)(OH)] and [Cu2(psmp)(OAc)2]-, demonstrate the anticipated 1:2 ligand/metal stoichiometry and show that the dimetallic binding site created for exogenous ligands possesses high inherent...... of antiferromagnetic coupling. This is corroborated computationally by broken-symmetry density functional theory, which for isotropic modeling of the coupling predicts an antiferromagnetic coupling strength of J = 70.5 cm-1....

Cold pressure welding - the mechanisms governing bonding

DEFF Research Database (Denmark)

Bay, Niels

1979-01-01

Investigations of the bonding surface in scanning electron microscope after fracture confirm the mechanisms of bond formation in cold pressure welding to be: fracture of work-hardened surface layer, surface expansion increasing the area of virgin surface, extrusion of virgin material through cracks...... of the original surface layer, and establishment of real contact and bonding between virgin material. This implies that normal pressure as well as surface expansion are basic parameters governing the bond strength. Experimental investigations of pressure welding Al-Al under plane strain compression in a specially...

Implicit ligand theory for relative binding free energies

Science.gov (United States)

Nguyen, Trung Hai; Minh, David D. L.

2018-03-01

Implicit ligand theory enables noncovalent binding free energies to be calculated based on an exponential average of the binding potential of mean force (BPMF)—the binding free energy between a flexible ligand and rigid receptor—over a precomputed ensemble of receptor configurations. In the original formalism, receptor configurations were drawn from or reweighted to the apo ensemble. Here we show that BPMFs averaged over a holo ensemble yield binding free energies relative to the reference ligand that specifies the ensemble. When using receptor snapshots from an alchemical simulation with a single ligand, the new statistical estimator outperforms the original.

Superior serum half life of albumin tagged TNF ligands

International Nuclear Information System (INIS)

Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

2010-01-01

Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

Quantitative chemogenomics: machine-learning models of protein-ligand interaction.

Science.gov (United States)

Andersson, Claes R; Gustafsson, Mats G; Strömbergsson, Helena

2011-01-01

Chemogenomics is an emerging interdisciplinary field that lies in the interface of biology, chemistry, and informatics. Most of the currently used drugs are small molecules that interact with proteins. Understanding protein-ligand interaction is therefore central to drug discovery and design. In the subfield of chemogenomics known as proteochemometrics, protein-ligand-interaction models are induced from data matrices that consist of both protein and ligand information along with some experimentally measured variable. The two general aims of this quantitative multi-structure-property-relationship modeling (QMSPR) approach are to exploit sparse/incomplete information sources and to obtain more general models covering larger parts of the protein-ligand space, than traditional approaches that focuses mainly on specific targets or ligands. The data matrices, usually obtained from multiple sparse/incomplete sources, typically contain series of proteins and ligands together with quantitative information about their interactions. A useful model should ideally be easy to interpret and generalize well to new unseen protein-ligand combinations. Resolving this requires sophisticated machine-learning methods for model induction, combined with adequate validation. This review is intended to provide a guide to methods and data sources suitable for this kind of protein-ligand-interaction modeling. An overview of the modeling process is presented including data collection, protein and ligand descriptor computation, data preprocessing, machine-learning-model induction and validation. Concerns and issues specific for each step in this kind of data-driven modeling will be discussed. © 2011 Bentham Science Publishers

Effects of electrostatic interactions on ligand dissociation kinetics

Science.gov (United States)

Erbaş, Aykut; de la Cruz, Monica Olvera; Marko, John F.

2018-02-01

We study unbinding of multivalent cationic ligands from oppositely charged polymeric binding sites sparsely grafted on a flat neutral substrate. Our molecular dynamics simulations are suggested by single-molecule studies of protein-DNA interactions. We consider univalent salt concentrations spanning roughly a 1000-fold range, together with various concentrations of excess ligands in solution. To reveal the ionic effects on unbinding kinetics of spontaneous and facilitated dissociation mechanisms, we treat electrostatic interactions both at a Debye-Hückel (DH) (or implicit ions, i.e., use of an electrostatic potential with a prescribed decay length) level and by the more precise approach of considering all ionic species explicitly in the simulations. We find that the DH approach systematically overestimates unbinding rates, relative to the calculations where all ion pairs are present explicitly in solution, although many aspects of the two types of calculation are qualitatively similar. For facilitated dissociation (FD) (acceleration of unbinding by free ligands in solution) explicit-ion simulations lead to unbinding at lower free-ligand concentrations. Our simulations predict a variety of FD regimes as a function of free-ligand and ion concentrations; a particularly interesting regime is at intermediate concentrations of ligands where nonelectrostatic binding strength controls FD. We conclude that explicit-ion electrostatic modeling is an essential component to quantitatively tackle problems in molecular ligand dissociation, including nucleic-acid-binding proteins.

[Supercomputer investigation of the protein-ligand system low-energy minima].

Science.gov (United States)

Oferkin, I V; Sulimov, A V; Katkova, E V; Kutov, D K; Grigoriev, F V; Kondakova, O A; Sulimov, V B

2015-01-01

The accuracy of the protein-ligand binding energy calculations and ligand positioning is strongly influenced by the choice of the docking target function. This work demonstrates the evaluation of the five different target functions used in docking: functions based on MMFF94 force field and functions based on PM7 quantum-chemical method accounting or without accounting the implicit solvent model (PCM, COSMO or SGB). For these purposes the ligand positions corresponding to the minima of the target function and the experimentally known ligand positions in the protein active site (crystal ligand positions) were compared. Each function was examined on the same test-set of 16 protein-ligand complexes. The new parallelized docking program FLM based on Monte Carlo search algorithm was developed to perform the comprehensive low-energy minima search and to calculate the protein-ligand binding energy. This study demonstrates that the docking target function based on the MMFF94 force field can be used to detect the crystal or near crystal positions of the ligand by the finding the low-energy local minima spectrum of the target function. The importance of solvent accounting in the docking process for the accurate ligand positioning is also shown. The accuracy of the ligand positioning as well as the correlation between the calculated and experimentally determined protein-ligand binding energies are improved when the MMFF94 force field is substituted by the new PM7 method with implicit solvent accounting.

Leadership and Governance in Regional Tourism

DEFF Research Database (Denmark)

Valente, Flavio Jose; Dredge, Dianne; Lohmann, Gui

2015-01-01

the idea that market-led governance offers a superior model of leadership for regional tourism. This paper adopts an embedded case study approach, undertaking a comparison of leadership in two RTOs that are operating in the same geographical location but under different governance regimes. Semi......-structured interviews with executives/leaders and stakeholders/followers were undertaken in two RTOs, a market-led organization and a government-led organization. The purpose of the study was to examine the influence of governance arrangements on the capacity of these RTOs to lead tourism. Findings reveal that while......The rise of neoliberal market management has contributed to an incontrovertible “truth” that regional tourism organizations (RTOs) established and led by business actors are more effective in leading regional tourism development. Despite these assertions, little evidence has surfaced to support...

Time-dependent photoluminescence spectroscopy as a tool to measure the ligand exchange kinetics on a quantum dot surface

NARCIS (Netherlands)

Koole, R.; Schapotschnikow, P.Z.; de Mello Donega, C.; Vlugt, T.J.H.; Meijerink, A.

2008-01-01

The exchange kinetics of native ligands that passivate CdSe quantum dots (hexadecylamine (HDA), trioctylphosphine oxide (TOPO), and trioctylphosphine (TOP)) by thiols is followed in situ. This is realized by measuring, in real-time, the decrease in emission intensity of the QDs upon addition of

LIGAND-BINDING SITES ON THE MYCOBACTERIUM TUBERCULOSIS UREASE

Directory of Open Access Journals (Sweden)

Lisnyak Yu. V.

2017-10-01

Full Text Available Introduction. Mycobacterium tuberculosis is the causative agent of tuberculosis that remains a serious medical and social health problem. Despite intensive efforts have been made in the past decade, there are no new efficient anti-tuberculosis drugs today, and that need is growing due to the spread of drug-resistant strains of M.tuberculosis. M. tuberculosis urease (MTU, being an important factor of the bacterium viability and virulence, is an attractive target for anti-tuberculosis drugs acting by inhibition of urease activity. However, the commercially available urease inhibitors are toxic and unstable, that prevent their clinical use. Therefore, new more potent anti-tuberculosis drugs inhibiting new targets are urgently needed. A useful tool for the search of novel inhibitors is a computational drug design. The inhibitor design is significantly easier if binding sites on the enzyme are identified in advance. This paper aimed to determine the probable ligand binding sites on the surface of M. tuberculosis urease. Methods. To identify ligand binding sites on MTU surface, сomputational solvent mapping method FTSite was applied by the use of MTU homology model we have built earlier. The method places molecular probes (small organic molecules containing various functional groups on a dense grid defined around the enzyme, and for each probe finds favorable positions. The selected poses are refined by free energy minimization, the low energy conformations are clustered, and the clusters are ranked on the basis of the average free energy. FTSite server outputs the protein residues delineating a binding sites and the probe molecules representing each cluster. To predict allosteric pockets on MTU, AlloPred and AlloSite servers were applied. AlloPred uses the normal mode analysis (NMA and models how the dynamics of a protein would be altered in the presence of a modulator at a specific pocket. Pockets on the enzyme are predicted using the Fpocket

Rational Ligand Design for U(VI) and Pu(IV)

International Nuclear Information System (INIS)

Szigethy, Geza

2009-01-01

Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO 2 2+ ). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative saturation, these

Rational Ligand Design for U(VI) and Pu(IV)

Energy Technology Data Exchange (ETDEWEB)

Szigethy, Geza [Univ. of California, Berkeley, CA (United States)

2009-08-12

Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO₂ ²⁺). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative

Cellular trafficking of quantum dot-ligand bioconjugates and their induction of changes in normal routing of unconjugated ligands

DEFF Research Database (Denmark)

Tekle, Christina; van Deurs, Bo; Sandvig, Kirsten

2008-01-01

Can quantum dots (Qdots) act as relevant intracellular probes to investigate routing of ligands in live cells? The intracellular trafficking of Qdots that were coupled to the plant toxin ricin, Shiga toxin, or the ligand transferrin (Tf) was studied by confocal fluorescence microscopy. The Tf...

Predicting Efficient Antenna Ligands for Tb(III) Emission

Energy Technology Data Exchange (ETDEWEB)

Samuel, Amanda P.S.; Xu, Jide; Raymond, Kenneth

2008-10-06

A series of highly luminescent Tb(III) complexes of para-substituted 2-hydroxyisophthalamide ligands (5LI-IAM-X) has been prepared (X = H, CH{sub 3}, (C=O)NHCH{sub 3}, SO{sub 3}{sup -}, NO{sub 2}, OCH{sub 3}, F, Cl, Br) to probe the effect of substituting the isophthalamide ring on ligand and Tb(III) emission in order to establish a method for predicting the effects of chromophore modification on Tb(III) luminescence. The energies of the ligand singlet and triplet excited states are found to increase linearly with the {pi}-withdrawing ability of the substituent. The experimental results are supported by time-dependent density functional theory (TD-DFT) calculations performed on model systems, which predict ligand singlet and triplet energies within {approx}5% of the experimental values. The quantum yield ({Phi}) values of the Tb(III) complex increases with the triplet energy of the ligand, which is in part due to the decreased non-radiative deactivation caused by thermal repopulation of the triplet. Together, the experimental and theoretical results serve as a predictive tool that can be used to guide the synthesis of ligands used to sensitize lanthanide luminescence.

Supramolecular architectures constructed using angular bipyridyl ligands

International Nuclear Information System (INIS)

Barnett, Sarah Ann

2003-01-01

This work details the synthesis and characterization of a series of coordination frameworks that are formed using bidentate angular N-donor ligands. Pyrimidine was reacted with metal(ll) nitrate salts. Reactions using Cd(NO 3 ) 2 receive particular focus and the analogous reactions using the linear ligand, pyrazine, were studied for comparison. In all cases, two-dimensional coordination networks were prepared. Structural diversity is observed for the Cd(ll) centres including metal-nitrate bridging. In contrast, first row transition metal nitrates form isostructural one-dimensional chains with only the bridging N-donor ligands generating polymeric propagation. The angular ligand, 2,4-bis(4-pyridyl)-1,3,5-triazine (dpt), was reacted with Cd(NO 3 ) 2 and Zn(NO 3 ) 2 . Whereas Zn(NO 3 ) 2 compounds exhibit solvent mediated polymorphism, a range of structures were obtained for the reactions with Cd(NO 3 ) 2 , including the first example of a doubly parallel interpenetrated 4.8 2 net. 4,7-phenanthroline, was reacted with various metal(ll) nitrates as well as cobalt(ll) and copper(ll) halides. The ability of 4,7-phenanthroline to act as both a N-donor ligand and a hydrogen bond acceptor has been discussed. Reactions of CuSCN with pyrimidine yield an unusual three-dimensional structure in which polymeric propagation is not a result of ligand bridging. The reaction of CuSCN with dpt yielded structural supramolecular isomers. (author)

Thermodynamics of Ligand Binding to a Heterogeneous RNA Population in the Malachite Green Aptamer

Science.gov (United States)

Sokoloski, Joshua E.; Dombrowski, Sarah E.; Bevilacqua, Philip C.

2011-01-01

The malachite green aptamer binds two closely related ligands, malachite green (MG) and tetramethylrosamine (TMR), with near equal affinity. The MG ligand consists of three phenyl rings emanating from a central carbon, while TMR has two of the three rings connected by an ether linkage. The binding pockets for MG and TMR in the aptamer, known from high-resolution structure, differ only in the conformation of a few nucleotides. Herein, we applied isothermal titration calorimetry (ITC) to compare the thermodynamics for binding of MG and TMR to the aptamer. Binding heat capacities were obtained from ITC titrations over the temperature range of 15 to 60 °C. Two temperature regimes were found for MG binding: one from 15 to 45 °C where MG bound with a large negative heat capacity and an apparent stoichiometry (n) of ~0.4, and another from 50 to 60 °C where MG bound with positive heat capacity and n~1.1. The binding of TMR, on the other hand, revealed only one temperature regime for binding, with a more modest negative heat capacity and n~1.2. The large difference in heat capacity between the two ligands suggests that significantly more conformational rearrangement occurs upon the binding of MG than TMR, which is consistent with differences in solvent accessible surface area calculated for available ligand-bound structures. Lastly, we note that binding stoichiometry of MG was improved not only by raising the temperature, but also by lowering the concentration of Mg2+ or increasing the time between ITC injections. These studies suggest that binding of a dynamical ligand to a functional RNA requires the RNA itself to have significant dynamics. PMID:22192051

Dynamic ligand-based pharmacophore modeling and virtual ...

Indian Academy of Sciences (India)

Five ligand-based pharmacophore models were generated from 40 different .... the Phase module of the Schrodinger program.35 Each model consisted of six types of ... ligand preparation included the OPLS_2005 force field and to retain the ...

Identification of VDR Antagonists among Nuclear Receptor Ligands Using Virtual Screening

Directory of Open Access Journals (Sweden)

Kelly Teske

2014-04-01

Full Text Available Herein, we described the development of two virtual screens to identify new vitamin D receptor (VDR antagonists among nuclear receptor (NR ligands. Therefore, a database of 14330 nuclear receptor ligands and their NR affinities was assembled using the online available “Binding Database.” Two different virtual screens were carried out in conjunction with a reported VDR crystal structure applying a stringent and less stringent pharmacophore model to filter docked NR ligand conformations. The pharmacophore models were based on the spatial orientation of the hydroxyl functionalities of VDR's natural ligands 1,25(OH2D3 and 25(OH2D3. The first virtual screen identified 32 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. All but nordihydroguaiaretic acid (NDGA are VDR ligands, which inhibited the interaction between VDR and coactivator peptide SRC2-3 with an IC50 value of 15.8 μM. The second screen identified 162 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. More than half of these ligands were developed to bind VDR followed by ERα/β ligands (26%, TRα/β ligands (7%, and LxRα/β ligands (7%. The binding between VDR and ERα ligand H6036 as well as TRα/β ligand triiodothyronine and a homoserine analog thereof was confirmed by fluorescence polarization.

Temperature-dependent surface density of alkylthiol monolayers on gold nanocrystals

Science.gov (United States)

Liu, Xuepeng; Lu, Pin; Zhai, Hua; Wu, Yucheng

2018-03-01

Atomistic molecular dynamics (MD) simulations are performed to study the surface density of passivating monolayers of alkylthiol chains on gold nanocrystals at temperatures ranging from 1 to 800 K. The results show that the surface density of alkylthiol monolayer reaches a maximum value at near room temperature (200-300 K), while significantly decreases with increasing temperature in the higher temperature region (> 300 {{K}}), and slightly decreases with decreasing temperature at low temperature (< 200 {{K}}). We find that the temperature dependence of surface ligand density in the higher temperature region is attributed to the substantial ligand desorption induced by the thermal fluctuation, while that at low temperature results from the reduction in entropy caused by the change in the ordering of passivating monolayer. These results are expected helpful to understand the temperature-dependent surface coverage of gold nanocrystals.

Water oxidation catalyzed by mononuclear ruthenium complexes with a 2,2'-bipyridine-6,6'-dicarboxylate (bda) ligand: how ligand environment influences the catalytic behavior.

Science.gov (United States)

Staehle, Robert; Tong, Lianpeng; Wang, Lei; Duan, Lele; Fischer, Andreas; Ahlquist, Mårten S G; Sun, Licheng; Rau, Sven

2014-02-03

A new water oxidation catalyst [Ru(III)(bda)(mmi)(OH2)](CF3SO3) (2, H2bda = 2,2'-bipyridine-6,6'-dicarboxylic acid; mmi = 1,3-dimethylimidazolium-2-ylidene) containing an axial N-heterocyclic carbene ligand and one aqua ligand was synthesized and fully characterized. The kinetics of catalytic water oxidation by 2 were measured using stopped-flow technique, and key intermediates in the catalytic cycle were probed by density functional theory calculations. While analogous Ru-bda water oxidation catalysts [Ru(bda)L2] (L = pyridyl ligands) are supposed to catalyze water oxidation through a bimolecular coupling pathway, our study points out that 2, surprisingly, undergoes a single-site water nucleophilic attack (acid-base) pathway. The diversion of catalytic mechanisms is mainly ascribed to the different ligand environments, from nonaqua ligands to an aqua ligand. Findings in this work provide some critical proof for our previous hypothesis about how alternation of ancillary ligands of water oxidation catalysts influences their catalytic efficiency.

A molecular dynamics study on the transport of a charged biomolecule in a polymeric adsorbent medium and its adsorption onto a charged ligand.

Science.gov (United States)

Riccardi, E; Wang, J-C; Liapis, A I

2010-08-28

The transport of a charged adsorbate biomolecule in a porous polymeric adsorbent medium and its adsorption onto the covalently immobilized ligands have been modeled and investigated using molecular dynamics modeling and simulations as the third part of a novel fundamental methodology developed for studying ion-exchange chromatography based bioseparations. To overcome computational challenges, a novel simulation approach is devised where appropriate atomistic and coarse grain models are employed simultaneously and the transport of the adsorbate is characterized through a number of locations representative of the progress of the transport process. The adsorbate biomolecule for the system studied in this work changes shape, orientation, and lateral position in order to proceed toward the site where adsorption occurs and exhibits decreased mass transport coefficients as it approaches closer to the immobilized ligand. Furthermore, because the ligands are surrounded by counterions carrying the same type of charge as the adsorbate biomolecule, it takes the biomolecule repeated attempts to approach toward a ligand in order to displace the counterions in the proximity of the ligand and to finally become adsorbed. The formed adsorbate-ligand complex interacts with the counterions and polymeric molecules and is found to evolve slowly and continuously from one-site (monovalent) interaction to multisite (multivalent) interactions. Such a transition of the nature of adsorption reduces the overall adsorption capacity of the ligands in the adsorbent medium and results in a type of surface exclusion effect. Also, the adsorption of the biomolecule also presents certain volume exclusion effects by not only directly reducing the pore volume and the availability of the ligands in the adjacent regions, but also causing the polymeric molecules to change to more compact structures that could further shield certain ligands from being accessible to subsequent adsorbate molecules. These

Systematic study of ligand structures of metal oxide EUV nanoparticle photoresists

KAUST Repository

Jiang, Jing

2015-03-19

Ligand stabilized metal oxide nanoparticle resists are promising candidates for EUV lithography due to their high sensitivity for high-resolution patterning and high etching resistance. As ligand exchange is responsible for the patterning mechanism, we systematically studied the influence of ligand structures of metal oxide EUV nanoparticles on their sensitivity and dissolution behavior. ZrO2 nanoparticles were protected with various aromatic ligands with electron withdrawing and electron donating groups. These nanoparticles have lower sensitivity compared to those with aliphatic ligands suggesting the structures of these ligands is more important than their pka on resist sensitivity. The influence of ligand structure was further studied by comparing the nanoparticles’ solubility for a single type ligand to mixtures of ligands. The mixture of nanoparticles showed improved pattern quality. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

LIBRA: LIgand Binding site Recognition Application.

Science.gov (United States)

Hung, Le Viet; Caprari, Silvia; Bizai, Massimiliano; Toti, Daniele; Polticelli, Fabio

2015-12-15

In recent years, structural genomics and ab initio molecular modeling activities are leading to the availability of a large number of structural models of proteins whose biochemical function is not known. The aim of this study was the development of a novel software tool that, given a protein's structural model, predicts the presence and identity of active sites and/or ligand binding sites. The algorithm implemented by ligand binding site recognition application (LIBRA) is based on a graph theory approach to find the largest subset of similar residues between an input protein and a collection of known functional sites. The algorithm makes use of two predefined databases for active sites and ligand binding sites, respectively, derived from the Catalytic Site Atlas and the Protein Data Bank. Tests indicate that LIBRA is able to identify the correct binding/active site in 90% of the cases analyzed, 90% of which feature the identified site as ranking first. As far as ligand binding site recognition is concerned, LIBRA outperforms other structure-based ligand binding sites detection tools with which it has been compared. The application, developed in Java SE 7 with a Swing GUI embedding a JMol applet, can be run on any OS equipped with a suitable Java Virtual Machine (JVM), and is available at the following URL: http://www.computationalbiology.it/software/LIBRAv1.zip. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Ligand mediated synthesis of AgInSe2 nanoparticles with tetragonal/orthorhombic crystal phases

International Nuclear Information System (INIS)

Abazović, Nadica D.; Čomor, Mirjana I.; Mitrić, Miodrag N.; Piscopiello, Emanuela; Radetić, Tamara; Janković, Ivana A.; Nedeljković, Jovan M.

2012-01-01

Nanosized AgInSe 2 particles (d ∼ 7–25 nm) were synthesized using colloidal chemistry method at 270 °C. As solvents/surface ligands 1-octadecene, trioctylphosphine, and oleylamine were used. It was shown that choice of ligand has crucial impact not only on final crystal phase of nanoparticles, but also at mechanism of crystal growth. X-ray diffraction and TEM/HRTEM techniques were used to identify obtained crystal phases and to measure average size and shape of nanoparticles. UV/Vis data were used to estimate band-gap energies of obtained samples. It was shown that presented routes can provide synthesis of nanoparticles with desired crystal phase (tetragonal and/or orthorhombic), with band-gap energies in the range from 1.25 to 1.53 eV.

Investigation of interaction between the Pt(II) ions and aminosilane-modified silica surface in heterogeneous system

Science.gov (United States)

Nowicki, Waldemar; Gąsowska, Anna; Kirszensztejn, Piotr

2016-05-01

UV-vis spectroscopy measurements confirmed the reaction in heterogeneous system between Pt(II) ions and ethylenediamine type ligand, n-(2-aminoethyl)-3-aminopropyl-trimethoxysilane, immobilized at the silica surface. The formation of complexes is a consequence of interaction between the amine groups from the ligand grafted onto SiO2 and ions of platinum. A potentiometric titration technique was to determine the stability constants of complexes of Pt(II) with immobilized insoluble ligand (SG-L), on the silica gel. The results show the formation of three surface complexes of the same type (PtHSG-L, Pt(HSG-L)2, PtSG-L) with SG-L ligand, in a wide range of pH for different Debye length. The concentration distribution of the complexes in a heterogeneous system is evaluated.

AMPA receptor ligands

DEFF Research Database (Denmark)

Strømgaard, Kristian; Mellor, Ian

2004-01-01

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

Ligand removal and photo-activation of CsPbBr3 quantum dots for enhanced optoelectronic devices.

Science.gov (United States)

Moyen, Eric; Kanwat, Anil; Cho, Sinyoung; Jun, Haeyeon; Aad, Roy; Jang, Jin

2018-05-10

Perovskite quantum dots have recently emerged as a promising light source for optoelectronic applications. However, integrating them into devices while preserving their outstanding optical properties remains challenging. Due to their ionic nature, perovskite quantum dots are extremely sensitive and degrade on applying the simplest processes. To maintain their colloidal stability, they are surrounded by organic ligands; these prevent efficient charge carrier injection in devices and have to be removed. Here we report on a simple method, where a moderate thermal process followed by exposure to UV in air can efficiently remove ligands and increase the photo-luminescence of the room temperature synthesized perovskite quantum dot thin films. Annealing is accompanied by a red shift of the emission wavelength, usually attributed to the coalescence and irreversible degradation of the quantum dots. We show that it is actually related to the relaxation of the quantum dots upon the ligand removal, without the creation of non-radiative recombining defects. The quantum dot surface, as devoid of ligands, is subsequently photo-oxidized and smoothened upon exposure to UV in air, which drastically enhances their photo-luminescence. This adequate combination of treatments improves by more than an order of magnitude the performances of perovskite quantum dot light emitting diodes.

New synthetic routes toward enantiopure nitrogen donor ligands.

Science.gov (United States)

Sala, Xavier; Rodríguez, Anna M; Rodríguez, Montserrat; Romero, Isabel; Parella, Teodor; von Zelewsky, Alexander; Llobet, Antoni; Benet-Buchholz, Jordi

2006-12-08

New polypyridylic chiral ligands, having either C3 or lower symmetry, have been prepared via a de novo construction of the pyridine nucleus by means of Kröhnke methodology in the key step. The chiral moieties of these ligands originate from the monoterpen chiral pool, namely (-)-alpha-pinene ((-)-14, (-)-15) and (-)-myrtenal ((-)-9, (-)-10). Extension of the above-mentioned asymmetric synthesis procedure to the preparation of enantiopure derivatives of some commonly used polypyridylic ligands has been achieved through a new aldehyde building block ((-)-16). As an example, the synthesis of a chiral derivative of N,N-bis(2-pyridylmethyl)ethylamine (bpea) ligand, (-)-19, has been performed to illustrate the viability of the method. The coordinative ability of the ligands has been tested through the synthesis and characterization of complexes [Mn((-)-19)Br2], (-)-20, and [RuCl((-)-10)(bpy)](BF4), (-)-21. Some preliminary results related to the enantioselective catalytic epoxidation of styrene with the ruthenium complex are also presented.

Cloud computing for protein-ligand binding site comparison.

Science.gov (United States)

Hung, Che-Lun; Hua, Guan-Jie

2013-01-01

The proteome-wide analysis of protein-ligand binding sites and their interactions with ligands is important in structure-based drug design and in understanding ligand cross reactivity and toxicity. The well-known and commonly used software, SMAP, has been designed for 3D ligand binding site comparison and similarity searching of a structural proteome. SMAP can also predict drug side effects and reassign existing drugs to new indications. However, the computing scale of SMAP is limited. We have developed a high availability, high performance system that expands the comparison scale of SMAP. This cloud computing service, called Cloud-PLBS, combines the SMAP and Hadoop frameworks and is deployed on a virtual cloud computing platform. To handle the vast amount of experimental data on protein-ligand binding site pairs, Cloud-PLBS exploits the MapReduce paradigm as a management and parallelizing tool. Cloud-PLBS provides a web portal and scalability through which biologists can address a wide range of computer-intensive questions in biology and drug discovery.

Automated ligand fitting by core-fragment fitting and extension into density

International Nuclear Information System (INIS)

Terwilliger, Thomas C.; Klei, Herbert; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

2006-01-01

An automated ligand-fitting procedure has been developed and tested on 9327 ligands and (F o − F c )exp(iϕ c ) difference density from macromolecular structures in the Protein Data Bank. A procedure for fitting of ligands to electron-density maps by first fitting a core fragment of the ligand to density and then extending the remainder of the ligand into density is presented. The approach was tested by fitting 9327 ligands over a wide range of resolutions (most are in the range 0.8-4.8 Å) from the Protein Data Bank (PDB) into (F o − F c )exp(iϕ c ) difference density calculated using entries from the PDB without these ligands. The procedure was able to place 58% of these 9327 ligands within 2 Å (r.m.s.d.) of the coordinates of the atoms in the original PDB entry for that ligand. The success of the fitting procedure was relatively insensitive to the size of the ligand in the range 10–100 non-H atoms and was only moderately sensitive to resolution, with the percentage of ligands placed near the coordinates of the original PDB entry for fits in the range 58–73% over all resolution ranges tested

Reverse Non-Equilibrium Molecular Dynamics Demonstrate That Surface Passivation Controls Thermal Transport at Semiconductor-Solvent Interfaces.

Science.gov (United States)

Hannah, Daniel C; Gezelter, J Daniel; Schaller, Richard D; Schatz, George C

2015-06-23

We examine the role played by surface structure and passivation in thermal transport at semiconductor/organic interfaces. Such interfaces dominate thermal transport in semiconductor nanomaterials owing to material dimensions much smaller than the bulk phonon mean free path. Utilizing reverse nonequilibrium molecular dynamics simulations, we calculate the interfacial thermal conductance (G) between a hexane solvent and chemically passivated wurtzite CdSe surfaces. In particular, we examine the dependence of G on the CdSe slab thickness, the particular exposed crystal facet, and the extent of surface passivation. Our results indicate a nonmonotonic dependence of G on ligand-grafting density, with interfaces generally exhibiting higher thermal conductance for increasing surface coverage up to ∼0.08 ligands/Å(2) (75-100% of a monolayer, depending on the particular exposed facet) and decreasing for still higher coverages. By analyzing orientational ordering and solvent penetration into the ligand layer, we show that a balance of competing effects is responsible for this nonmonotonic dependence. Although the various unpassivated CdSe surfaces exhibit similar G values, the crystal structure of an exposed facet nevertheless plays an important role in determining the interfacial thermal conductance of passivated surfaces, as the density of binding sites on a surface determines the ligand-grafting densities that may ultimately be achieved. We demonstrate that surface passivation can increase G relative to a bare surface by roughly 1 order of magnitude and that, for a given extent of passivation, thermal conductance can vary by up to a factor of ∼2 between different surfaces, suggesting that appropriately tailored nanostructures may direct heat flow in an anisotropic fashion for interface-limited thermal transport.

Hydrophobic patches on protein surfaces

NARCIS (Netherlands)

Lijnzaad, P.

2007-01-01

Hydrophobicity is a prime determinant of the structure and function of proteins. It is the driving force behind the folding of soluble proteins, and when exposed on the surface, it is frequently involved in recognition and binding of ligands and other proteins. The energetic cost of

Interaction between alkaline earth cations and oxo-ligands. DFT study of the affinity of the Ca2+ cation for carbonyl ligands.

Science.gov (United States)

da Costa, Leonardo Moreira; Carneiro, José Walkimar de Mesquita; Romeiro, Gilberto Alves; Paes, Lilian Weitzel Coelho

2011-02-01

The affinity of the Ca(2+) ion for a set of substituted carbonyl ligands was analyzed with both the DFT (B3LYP/6-31+G(d)) and semi-empirical (PM6) methods. Two types of ligands were studied: a set of monosubstituted [O=CH(R)] and a set of disubstituted ligands [O=C(R)(2)] (R=H, F, Cl, Br, OH, OCH(3), CH(3), CN, NH(2) and NO(2)), with R either directly bound to the carbonyl carbon atom or to the para position of a phenyl ring. The interaction energy was calculated to quantify the affinity of the Ca(2+) cation for the ligands. Geometric and electronic parameters were correlated with the intensity of the metal-ligand interaction. The electronic nature of the substituent is the main parameter that determines the interaction energy. Donor groups make the interaction energy more negative (stabilizing the complex formed), while acceptor groups make the interaction energy less negative (destabilizing the complex formed).

Coupled metal partitioning dynamics and toxicodynamics at biointerfaces: a theory beyond the biotic ligand model framework.

Science.gov (United States)

Duval, Jérôme F L

2016-04-14

A mechanistic understanding of the processes governing metal toxicity to microorganisms (bacteria, algae) calls for an adequate formulation of metal partitioning at biointerfaces during cell exposure. This includes the account of metal transport dynamics from bulk solution to biomembrane and the kinetics of metal internalisation, both potentially controlling the intracellular and surface metal fractions that originate cell growth inhibition. A theoretical rationale is developed here for such coupled toxicodynamics and interfacial metal partitioning dynamics under non-complexing medium conditions with integration of the defining cell electrostatic properties. The formalism explicitly considers intertwined metal adsorption at the biointerface, intracellular metal excretion, cell growth and metal depletion from bulk solution. The theory is derived under relevant steady-state metal transport conditions on the basis of coupled Nernst-Planck equation and continuous logistic equation modified to include metal-induced cell growth inhibition and cell size changes. Computational examples are discussed to identify limitations of the classical Biotic Ligand Model (BLM) in evaluating metal toxicity over time. In particular, BLM is shown to severely underestimate metal toxicity depending on cell exposure time, metal internalisation kinetics, cell surface electrostatics and initial cell density. Analytical expressions are provided for the interfacial metal concentration profiles in the limit where cell-growth is completely inhibited. A rigorous relationship between time-dependent cell density and metal concentrations at the biosurface and in bulk solution is further provided, which unifies previous equations formulated by Best and Duval under constant cell density and cell size conditions. The theory is sufficiently flexible to adapt to toxicity scenarios with involved cell survival-death processes.

Synthesis and Structure Determination of a New Au₂₀ Nanocluster Protected by Tripodal Tetraphosphine Ligands

Energy Technology Data Exchange (ETDEWEB)

Chen, Jing [Brown Univ., Providence, RI (United States); Zhang, Qianfan [Brown Univ., Providence, RI (United States); Williard, Paul G. [Brown Univ., Providence, RI (United States); Wang, Lai-Sheng [Brown Univ., Providence, RI (United States)

2014-03-31

We report the synthesis and structure determination of a new Au₂₀ nanocluster coordinated by four tripodal tetraphosphine (PP₃) ligands {PP₃ = tris[2-(diphenylphosphino)ethyl]phosphine}. Single-crystal Xray crystallography and electrospray ionization mass spectrometry show that the cluster assembly can be formulated as [Au₂₀(PP₃)₄]Cl₄. The Au₂₀ cluster consists of an icosahedral Au₁₃ core and a seven-Au-atom partial outer shell arranged in a local C₃ symmetry. One PP₃ ligand coordinates to four Au atoms in the outer shell, while the other three PP₃ ligands coordinate to one Au atom from the outer shell and three Au atoms from the surface of the Au₁₃ core, giving rise to an overall chiral 16-electron Au cluster core with C3 symmetry.

Models of protein–ligand crystal structures: trust, but verify

Science.gov (United States)

Deller, Marc C.

2015-01-01

X-ray crystallography provides the most accurate models of protein–ligand structures. These models serve as the foundation of many computational methods including structure prediction, molecular modelling, and structure-based drug design. The success of these computational methods ultimately depends on the quality of the underlying protein–ligand models. X-ray crystallography offers the unparalleled advantage of a clear mathematical formalism relating the experimental data to the protein–ligand model. In the case of X-ray crystallography, the primary experimental evidence is the electron density of the molecules forming the crystal. The first step in the generation of an accurate and precise crystallographic model is the interpretation of the electron density of the crystal, typically carried out by construction of an atomic model. The atomic model must then be validated for fit to the experimental electron density and also for agreement with prior expectations of stereochemistry. Stringent validation of protein–ligand models has become possible as a result of the mandatory deposition of primary diffraction data, and many computational tools are now available to aid in the validation process. Validation of protein–ligand complexes has revealed some instances of overenthusiastic interpretation of ligand density. Fundamental concepts and metrics of protein–ligand quality validation are discussed and we highlight software tools to assist in this process. It is essential that end users select high quality protein–ligand models for their computational and biological studies, and we provide an overview of how this can be achieved. PMID:25665575

Models of protein-ligand crystal structures: trust, but verify.

Science.gov (United States)

Deller, Marc C; Rupp, Bernhard

2015-09-01

X-ray crystallography provides the most accurate models of protein-ligand structures. These models serve as the foundation of many computational methods including structure prediction, molecular modelling, and structure-based drug design. The success of these computational methods ultimately depends on the quality of the underlying protein-ligand models. X-ray crystallography offers the unparalleled advantage of a clear mathematical formalism relating the experimental data to the protein-ligand model. In the case of X-ray crystallography, the primary experimental evidence is the electron density of the molecules forming the crystal. The first step in the generation of an accurate and precise crystallographic model is the interpretation of the electron density of the crystal, typically carried out by construction of an atomic model. The atomic model must then be validated for fit to the experimental electron density and also for agreement with prior expectations of stereochemistry. Stringent validation of protein-ligand models has become possible as a result of the mandatory deposition of primary diffraction data, and many computational tools are now available to aid in the validation process. Validation of protein-ligand complexes has revealed some instances of overenthusiastic interpretation of ligand density. Fundamental concepts and metrics of protein-ligand quality validation are discussed and we highlight software tools to assist in this process. It is essential that end users select high quality protein-ligand models for their computational and biological studies, and we provide an overview of how this can be achieved.

Quantitative analysis of protein-ligand interactions by NMR.

Science.gov (United States)

Furukawa, Ayako; Konuma, Tsuyoshi; Yanaka, Saeko; Sugase, Kenji

2016-08-01

Protein-ligand interactions have been commonly studied through static structures of the protein-ligand complex. Recently, however, there has been increasing interest in investigating the dynamics of protein-ligand interactions both for fundamental understanding of the underlying mechanisms and for drug development. NMR is a versatile and powerful tool, especially because it provides site-specific quantitative information. NMR has widely been used to determine the dissociation constant (KD), in particular, for relatively weak interactions. The simplest NMR method is a chemical-shift titration experiment, in which the chemical-shift changes of a protein in response to ligand titration are measured. There are other quantitative NMR methods, but they mostly apply only to interactions in the fast-exchange regime. These methods derive the dissociation constant from population-averaged NMR quantities of the free and bound states of a protein or ligand. In contrast, the recent advent of new relaxation-based experiments, including R2 relaxation dispersion and ZZ-exchange, has enabled us to obtain kinetic information on protein-ligand interactions in the intermediate- and slow-exchange regimes. Based on R2 dispersion or ZZ-exchange, methods that can determine the association rate, kon, dissociation rate, koff, and KD have been developed. In these approaches, R2 dispersion or ZZ-exchange curves are measured for multiple samples with different protein and/or ligand concentration ratios, and the relaxation data are fitted to theoretical kinetic models. It is critical to choose an appropriate kinetic model, such as the two- or three-state exchange model, to derive the correct kinetic information. The R2 dispersion and ZZ-exchange methods are suitable for the analysis of protein-ligand interactions with a micromolar or sub-micromolar dissociation constant but not for very weak interactions, which are typical in very fast exchange. This contrasts with the NMR methods that are used

Inorganic-ligand exchanging time effect in PbS quantum dot solar cell

International Nuclear Information System (INIS)

Kim, Byung-Sung; Hong, John; Hou, Bo; Cho, Yuljae; Sohn, Jung Inn; Cha, SeungNam; Kim, Jong Min

2016-01-01

We investigate time-dependent inorganic ligand exchanging effect and photovoltaic performance of lead sulfide (PbS) nanocrystal films. With optimal processing time, volume shrinkage induced by residual oleic acid of the PbS colloidal quantum dot (CQD) was minimized and a crack-free film was obtained with improved flatness. Furthermore, sufficient surface passivation significantly increased the packing density by replacing from long oleic acid to a short iodide molecule. It thus facilities exciton dissociation via enhanced charge carrier transport in PbS CQD films, resulting in the improved power conversion efficiency from 3.39% to 6.62%. We also found that excess iodine ions on the PbS surface rather hinder high photovoltaic performance of the CQD solar cell.

Inorganic-ligand exchanging time effect in PbS quantum dot solar cell

Energy Technology Data Exchange (ETDEWEB)

Kim, Byung-Sung; Hong, John; Hou, Bo; Cho, Yuljae; Sohn, Jung Inn, E-mail: junginn.sohn@eng.ox.ac.uk, E-mail: seungnam.cha@eng.ox.ac.uk; Cha, SeungNam, E-mail: junginn.sohn@eng.ox.ac.uk, E-mail: seungnam.cha@eng.ox.ac.uk [Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ (United Kingdom); Kim, Jong Min [Department of Engineering, University of Cambridge, 9 JJ Thomson Avenue, Cambridge CB3 0FA (United Kingdom)

2016-08-08

We investigate time-dependent inorganic ligand exchanging effect and photovoltaic performance of lead sulfide (PbS) nanocrystal films. With optimal processing time, volume shrinkage induced by residual oleic acid of the PbS colloidal quantum dot (CQD) was minimized and a crack-free film was obtained with improved flatness. Furthermore, sufficient surface passivation significantly increased the packing density by replacing from long oleic acid to a short iodide molecule. It thus facilities exciton dissociation via enhanced charge carrier transport in PbS CQD films, resulting in the improved power conversion efficiency from 3.39% to 6.62%. We also found that excess iodine ions on the PbS surface rather hinder high photovoltaic performance of the CQD solar cell.

New synthetic routes toward enantiopure nitrogen donor ligands

OpenAIRE

Sala, Xavier; Rodríguez, Anna M.; Rodríguez, Montserrat; Romero, Isabel; Parella, Teodor; Zelewsky, Alexander von; Llobet, Antoni; Benet-Buchholz, Jordi

2008-01-01

New polypyridylic chiral ligands, having either C₃ or lower symmetry, have been prepared via a de novo construction of the pyridine nucleus by means of Kröhnke methodology in the key step. The chiral moieties of these ligands originate from the monoterpen chiral pool, namely (-)-α-pinene ((-)-14, (-)-15) and (-)-myrtenal ((-)-9, (-)-10). Extension of the above-mentioned asymmetric synthesis procedure to the preparation of enantiopure derivatives of some commonly used polypyridylic ligands has...

Effects of PPARγ ligands on vascular tone.

Science.gov (United States)

Salomone, Salvatore; Drago, Filippo

2012-06-01

Peroxisome Proliferator-Activated Receptor γ (PPARγ), originally described as a transcription factor for genes of carbohydrate and lipid metabolism, has been more recently studied in the context of cardiovascular pathophysiology. Here, we review the available data on PPARγ ligands as modulator of vascular tone. PPARγ ligands include: thiazolidinediones (used in the treatment of type 2 diabetes mellitus), glitazars (bind and activate both PPARγ and PPARα), and other experimental drugs (still in development) that exploit the chemistry of thiazolidinediones as a scaffold for PPARγ-independent pharmacological properties. In this review, we examine both short (mostly from in vitro data)- and long (mostly from in vivo data)-term effects of PPARγ ligands that extend from PPARγ-independent vascular effects to PPARγ-dependent gene expression. Because endothelium is a master regulator of vascular tone, we have attempted to differentiate between endothelium-dependent and endothelium-independent effects of PPARγ ligands. Based on available data, we conclude that PPARγ ligands appear to influence vascular tone in different experimental paradigms, most often in terms of vasodilatation (potentially increasing blood flow to some tissues). These effects on vascular tone, although potentially beneficial, must be weighed against specific cardiovascular warnings that may apply to some drugs, such as rosiglitazone.

Regulation mechanisms of the FLT3-ligand after irradiation

International Nuclear Information System (INIS)

Prat-Lepesant, M.

2005-06-01

The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia. The results indicated that the concentration of Flt3 ligand in the blood reflects the bone marrow status, and that the follow-up of plasma Flt3 ligand concentration could give predictive information about the bone marrow function and the duration and severity of pancytopenia and thrombocytopenia. Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. We thus developed a study in the mouse model. The results indicated that the variations in plasma Flt3 ligand variations were not solely due to a balance between its production by lymphoid cells and its consumption by hematopoietic cells. Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. These results also suggest that the Flt3 ligand is a main systemic regulator of hematopoiesis

Sensing Conformational Changes in DNA upon Ligand Binding Using QCM-D. Polyamine Condensation and Rad51 Extension of DNA Layers

KAUST Repository

Sun, Lu; Frykholm, Karolin; Fornander, Louise H.; Svedhem, Sofia; Westerlund, Fredrik; Å kerman, Bjö rn

2014-01-01

© 2014 American Chemical Society. Biosensors, in which binding of ligands is detected through changes in the optical or electrochemical properties of a DNA layer confined to the sensor surface, are important tools for investigating DNA interactions

Prediction of ligand effects in platinum-amyloid-β coordination.

Science.gov (United States)

Turner, Matthew; Deeth, Robert J; Platts, James A

2017-08-01

Ligand field molecular mechanics (LFMM) and semi-empirical Parametric Model 7 (PM7) methods are applied to a series of six Pt II -Ligand systems binding to the N-terminal domain of the amyloid-β (Aβ) peptide. Molecular dynamics using a combined LFMM/Assisted Model Building with Energy Refinement (AMBER) approach is used to explore the conformational freedom of the peptide fragment, and identifies favourable platinum binding modes and peptide conformations for each ligand investigated. Platinum coordination is found to depend on the nature of the ligand, providing evidence that binding mode may be controlled by suitable ligand design. Boltzmann populations at 310K indicate that each Pt-Aβ complex has a small number of thermodynamically accessible states. Ramachandran maps are constructed for the sampled Pt-Aβ conformations and secondary structural analysis of the obtained complex structures is performed and contrasted with the free peptide; coordination of these platinum complexes disrupts existing secondary structure in the Aβ peptide and promotes formation of ligand-specific turn-type secondary structure. Copyright © 2017 Elsevier Inc. All rights reserved.

Precipitation and growth of zinc sulfide nanoparticles in the presence of thiol-containing natural organic ligands.

Science.gov (United States)

Lau, Boris L T; Hsu-Kim, Heileen

2008-10-01

In sulfidic aquatic systems, metal sulfides can control the mobility and bioavailability of trace metal pollutants such as zinc, mercury, and silver. Nanoparticles of ZnS and other metal sulfides are known to exist in oxic and anoxic waters. However, the processes that lead to their persistence in the aquatic environment are relatively unknown. The objective of this study was to evaluate the importance of dissolved natural organics in stabilizing nanoparticulate ZnS that precipitates under environmentally relevant conditions. Precipitation and growth of ZnS particles were investigated in the presence of dissolved humic acid and low-molecular weight organic acids that are prevalent in sediment porewater. Dynamic light scattering was used to monitor the hydrodynamic diameter of particles precipitating in laboratory solutions. Zn speciation was also measured by filtering the ZnS solutions (precipitation experiments and not to the dissolved organic ligands. X-ray photoelectron spectroscopy and electron microscopy were used to confirm that amorphous particles containing Zn and S were precipitating in the suspensions. Observed growth rates of ZnS particles varied by orders of magnitude, depending on the type and concentration of organic ligand in solution. In the presence of humic acid and thiol-containing ligands (cysteine, glutathione, and thioglycolate), observed growth rates decreased by 1-3 orders of magnitude relative to controls without the ligands. In contrast, growth rates of the particles were consistently within 1 order of magnitude of the ligand-free control when oxygen- and amine-containing ligands (oxalate, serine, and glycolate) were present Furthermore, particle growth rates decreased with an increase in thiol concentration and increased with NaNO3 electrolyte concentration. These studies suggest that specific surface interactions with thiol-containing organics may be one factor that contributes to the persistence of naturally occurring and anthropogenic

A grand unified model for liganded gold clusters

Science.gov (United States)

Xu, Wen Wu; Zhu, Beien; Zeng, Xiao Cheng; Gao, Yi

2016-12-01

A grand unified model (GUM) is developed to achieve fundamental understanding of rich structures of all 71 liganded gold clusters reported to date. Inspired by the quark model by which composite particles (for example, protons and neutrons) are formed by combining three quarks (or flavours), here gold atoms are assigned three `flavours' (namely, bottom, middle and top) to represent three possible valence states. The `composite particles' in GUM are categorized into two groups: variants of triangular elementary block Au3(2e) and tetrahedral elementary block Au4(2e), all satisfying the duet rule (2e) of the valence shell, akin to the octet rule in general chemistry. The elementary blocks, when packed together, form the cores of liganded gold clusters. With the GUM, structures of 71 liganded gold clusters and their growth mechanism can be deciphered altogether. Although GUM is a predictive heuristic and may not be necessarily reflective of the actual electronic structure, several highly stable liganded gold clusters are predicted, thereby offering GUM-guided synthesis of liganded gold clusters by design.

Reversible Size Control of Silver Nanoclusters via Ligand-exchange

KAUST Repository

Bootharaju, Megalamane Siddaramappa

2015-05-21

The properties of atomically monodisperse noble metal nanoclusters (NCs) are intricately intertwined with their precise molecular formula. The vast majority of size-specific NC syntheses start from the reduction of the metal salt and thiol ligand mixture. Only in gold was it recently shown that ligand-exchange could induce the growth of NCs from one atomically precise species to another; a process of yet unknown reversibility. Here, we present a process for the ligand-exchange-induced growth of atomically precise silver NCs, in a biphasic liquid-liquid system, which is particularly of interest because of its complete reversibility and ability to occur at room temperature. We explore this phenomenon in-depth using Ag35(SG)18 [SG= glutathionate] and Ag44(4-FTP)30 [4-FTP= 4-fluorothiophenol] as model systems. We show that the ligand-exchange conversion of Ag35(SG)18 into Ag44(4-FTP)30 is rapid (< 5 min) and direct, while the reverse process proceeds slowly through intermediate cluster sizes. We adapt a recently developed theory of reverse Ostwald ripening to model the NCs’ interconvertibility. The model’s predictions are in good agreement with the experimental observations, and they highlight the importance of small changes in the ligand-metal binding energy in determining the final equilibrium NC size. Based on the insight provided by this model, we demonstrated experimentally that by varying the choice of ligands, ligand-exchange can be used to obtain different sized NCs. The findings in this work establish ligand-exchange as a versatile tool for tuning cluster sizes.

Reversible Size Control of Silver Nanoclusters via Ligand-exchange

KAUST Repository

Bootharaju, Megalamane Siddaramappa; Burlakov, Victor M.; Besong, Tabot M.D.; Joshi, Chakra Prasad; AbdulHalim, L; Black, David; Whetten, Robert; Goriely, Alain; Bakr, Osman

2015-01-01

The properties of atomically monodisperse noble metal nanoclusters (NCs) are intricately intertwined with their precise molecular formula. The vast majority of size-specific NC syntheses start from the reduction of the metal salt and thiol ligand mixture. Only in gold was it recently shown that ligand-exchange could induce the growth of NCs from one atomically precise species to another; a process of yet unknown reversibility. Here, we present a process for the ligand-exchange-induced growth of atomically precise silver NCs, in a biphasic liquid-liquid system, which is particularly of interest because of its complete reversibility and ability to occur at room temperature. We explore this phenomenon in-depth using Ag35(SG)18 [SG= glutathionate] and Ag44(4-FTP)30 [4-FTP= 4-fluorothiophenol] as model systems. We show that the ligand-exchange conversion of Ag35(SG)18 into Ag44(4-FTP)30 is rapid (< 5 min) and direct, while the reverse process proceeds slowly through intermediate cluster sizes. We adapt a recently developed theory of reverse Ostwald ripening to model the NCs’ interconvertibility. The model’s predictions are in good agreement with the experimental observations, and they highlight the importance of small changes in the ligand-metal binding energy in determining the final equilibrium NC size. Based on the insight provided by this model, we demonstrated experimentally that by varying the choice of ligands, ligand-exchange can be used to obtain different sized NCs. The findings in this work establish ligand-exchange as a versatile tool for tuning cluster sizes.

Reaction and Aggregation Dynamics of Cell Surface Receptors

Science.gov (United States)

Wang, Michelle Dong

This dissertation is composed of both theoretical and experimental studies of cell surface receptor reaction and aggregation. Project I studies the reaction rate enhancement due to surface diffusion of a bulk dissolved ligand with its membrane embedded target, using numerical calculations. The results show that the reaction rate enhancement is determined by ligand surface adsorption and desorption kinetic rates, surface and bulk diffusion coefficients, and geometry. In particular, we demonstrate that the ligand surface adsorption and desorption kinetic rates, rather than their ratio (the equilibrium constant), are important in rate enhancement. The second and third projects are studies of acetylcholine receptor clusters on cultured rat myotubes using fluorescence techniques after labeling the receptors with tetramethylrhodamine -alpha-bungarotoxin. The second project studies when and where the clusters form by making time-lapse movies. The movies are made from overlay of the pseudocolored total internal reflection fluorescence (TIRF) images of the cluster, and the schlieren images of the cell cultures. These movies are the first movies made using TIRF, and they clearly show the cluster formation from the myoblast fusion, the first appearance of clusters, and the eventual disappearance of clusters. The third project studies the fine structural features of individual clusters observed under TIRF. The features were characterized with six parameters by developing a novel fluorescence technique: spatial fluorescence autocorrelation. These parameters were then used to study the feature variations with age, and with treatments of drugs (oligomycin and carbachol). The results show little variation with age. However, drug treatment induced significant changes in some parameters. These changes were different for oligomycin and carbachol, which indicates that the two drugs may eliminate clusters through different mechanisms.

Glutamate receptor ligands

DEFF Research Database (Denmark)

Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

2002-01-01

Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

Crystal structure of LGR4-Rspo1 complex: insights into the divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors (LGRs).

Science.gov (United States)

Xu, Jin-Gen; Huang, Chunfeng; Yang, Zhengfeng; Jin, Mengmeng; Fu, Panhan; Zhang, Ni; Luo, Jian; Li, Dali; Liu, Mingyao; Zhou, Yan; Zhu, Yongqun

2015-01-23

Leucine-rich repeat G-protein-coupled receptors (LGRs) are a unique class of G-protein-coupled receptors characterized by a large extracellular domain to recognize ligands and regulate many important developmental processes. Among the three groups of LGRs, group B members (LGR4-6) recognize R-spondin family proteins (Rspo1-4) to stimulate Wnt signaling. In this study, we successfully utilized the "hybrid leucine-rich repeat technique," which fused LGR4 with the hagfish VLR protein, to obtain two recombinant human LGR4 proteins, LGR415 and LGR49. We determined the crystal structures of ligand-free LGR415 and the LGR49-Rspo1 complex. LGR4 exhibits a twisted horseshoe-like structure. Rspo1 adopts a flat and β-fold architecture and is bound in the concave surface of LGR4 in the complex through electrostatic and hydrophobic interactions. All the Rspo1-binding residues are conserved in LGR4-6, suggesting that LGR4-6 bind R-spondins through an identical surface. Structural analysis of our LGR4-Rspo1 complex with the previously determined LGR4 and LGR5 structures revealed that the concave surface of LGR4 is the sole binding site for R-spondins, suggesting a one-site binding model of LGR4-6 in ligand recognition. The molecular mechanism of LGR4-6 is distinct from the two-step mechanism of group A receptors LGR1-3 and the multiple-interface binding model of group C receptors LGR7-8, suggesting LGRs utilize the divergent mechanisms for ligand recognition. Our structures, together with previous reports, provide a comprehensive understanding of the ligand recognition by LGRs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Targeting nanoparticles to M cells with non-peptidic ligands for oral vaccination

OpenAIRE

Fievez, Virginie; Plapied, Laurence; des Rieux, Anne; Pourcelle, Vincent; Freichels, Hélène; Wascotte, Valentine; Vanderhaegen, Marie-Lyse; Jérôme, Christine; Vanderplasschen, Alain; Marchand-Brynaert, Jacqueline; Préat, Véronique

2009-01-01

The presence of RGD on nanoparticles allows the targeting of β1 integrins at the apical surface of human M cells and the enhancement of an immune response after oral immunization. To check the hypothesis that non-peptidic ligands targeting intestinal M cells or APCs would be more efficient for oral immunization than RGD, novel non-peptidic and peptidic analogs (RGD peptidomimitic (RGDp), LDV derivative (LDVd) and LDV peptidomimetic (LDVp)) as well as mannose were grafted on the PEG chain of P...

Automated identification of crystallographic ligands using sparse-density representations

International Nuclear Information System (INIS)

Carolan, C. G.; Lamzin, V. S.

2014-01-01

A novel procedure for identifying ligands in macromolecular crystallographic electron-density maps is introduced. Density clusters in such maps can be rapidly attributed to one of 82 different ligands in an automated manner. A novel procedure for the automatic identification of ligands in macromolecular crystallographic electron-density maps is introduced. It is based on the sparse parameterization of density clusters and the matching of the pseudo-atomic grids thus created to conformationally variant ligands using mathematical descriptors of molecular shape, size and topology. In large-scale tests on experimental data derived from the Protein Data Bank, the procedure could quickly identify the deposited ligand within the top-ranked compounds from a database of candidates. This indicates the suitability of the method for the identification of binding entities in fragment-based drug screening and in model completion in macromolecular structure determination

CXCR4 Ligands : The Next Big Hit?

NARCIS (Netherlands)

Walenkamp, Annemiek M. E.; Lapa, Constantin; Herrmann, Ken; Wester, Hans-Juergen

2017-01-01

The G protein-coupled protein receptor C-X-C chemokine receptor 4 (CXCR4) is an attractive target for cancer diagnosis and treatment, as it is overexpressed in many solid and hematologic cancers. Binding of its ligand, C-X-C chemokine ligand 12 (CXCL12), results in receptor internalization and

Polymerization catalysts containing electron-withdrawing amide ligands

Science.gov (United States)

Watkin, John G.; Click, Damon R.

2002-01-01

The present invention describes methods of making a series of amine-containing organic compounds which are used as ligands for group 3-10 and lanthanide metal compounds. The ligands have electron-withdrawing groups bonded to them. The metal compounds, when combined with a cocatalyst, are catalysts for the polymerization of olefins.

Immobilisation of ligands by radio-derivatized polymers

International Nuclear Information System (INIS)

Varga, J.M.; Fritsch, P.

1995-01-01

The invention relates to radio-derivatized polymers and a method of producing them by contacting non-polymerizable conjugands with radiolysable polymers in the presence of irradiation. The resulting radio-derivatized polymers can be further linked with ligand of organic or inorganic nature to immobilize such ligands. 2 figs., 5 tabs

Synthesis and study of new oxazoline-based ligands

OpenAIRE

Tilliet, Mélanie

2008-01-01

This thesis deals with the study of oxazoline-based ligands in metal-catalyzed asymmetric reactions. The first part describes the synthesis of six new bifunctinal pyridine-bis(oxazoline) ligands and their applications in asymmetric metal-catalysis. These ligands, in addition to a Lewis acid coordination site, are equipped with a Lewis basic part in the 4-position of the oxazoline rings. Dual activation by means of this system was probed in cyanide addition to aldehydes. The second part is con...

Selectivity in ligand recognition of G-quadruplex loops.

Science.gov (United States)

Campbell, Nancy H; Patel, Manisha; Tofa, Amina B; Ghosh, Ragina; Parkinson, Gary N; Neidle, Stephen

2009-03-03

A series of disubstituted acridine ligands have been cocrystallized with a bimolecular DNA G-quadruplex. The ligands have a range of cyclic amino end groups of varying size. The crystal structures show that the diagonal loop in this quadruplex results in a large cavity for these groups, in contrast to the steric constraints imposed by propeller loops in human telomeric quadruplexes. We conclude that the nature of the loop has a significant influence on ligand selectivity for particular quadruplex folds.

Surface passivity largely governs the bioaccessibility of nickel-based powder particles at human exposure conditions.

Science.gov (United States)

Hedberg, Yolanda S; Herting, Gunilla; Latvala, Siiri; Elihn, Karine; Karlsson, Hanna L; Odnevall Wallinder, Inger

2016-11-01

The European chemical framework REACH requires that hazards and risks posed by chemicals, including alloys and metals, are identified and proven safe for humans and the environment. Therefore, differences in bioaccessibility in terms of released metals in synthetic biological fluids (different pH (1.5-7.4) and composition) that are relevant for different human exposure routes (inhalation, ingestion, and dermal contact) have been assessed for powder particles of an alloy containing high levels of nickel (Inconel 718, 57 wt% nickel). This powder is compared with the bioaccessibility of two nickel-containing stainless steel powders (AISI 316L, 10-12% nickel) and with powders representing their main pure alloy constituents: two nickel metal powders (100% nickel), two iron metal powders and two chromium metal powders. X-ray photoelectron spectroscopy, microscopy, light scattering, and nitrogen absorption were employed for the particle and surface oxide characterization. Atomic absorption spectroscopy was used to quantify released amounts of metals in solution. Cytotoxicity (Alamar blue assay) and DNA damage (comet assay) of the Inconel powder were assessed following exposure of the human lung cell line A549, as well as its ability to generate reactive oxygen species (DCFH-DA assay). Despite its high nickel content, the Inconel alloy powder did not release any significant amounts of metals and did not induce any toxic response. It is concluded, that this is related to the high surface passivity of the Inconel powder governed by its chromium-rich surface oxide. Read-across from the pure metal constituents is hence not recommended either for this or any other passive alloy. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-γ ligand, rosiglitazone

International Nuclear Information System (INIS)

Wakui, Yuta; Inoue, Jun; Ueno, Yoshiyuki; Fukushima, Koji; Kondo, Yasuteru; Kakazu, Eiji; Obara, Noriyuki; Kimura, Osamu; Shimosegawa, Tooru

2010-01-01

Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-α, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPARα ligand, bezafibrate, and a PPARγ ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced the amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPARγ, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-α-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.

Scattering-Type Surface-Plasmon-Resonance Biosensors

Science.gov (United States)

Wang, Yu; Pain, Bedabrata; Cunningham, Thomas; Seshadri, Suresh

2005-01-01

Biosensors of a proposed type would exploit scattering of light by surface plasmon resonance (SPR). Related prior biosensors exploit absorption of light by SPR. Relative to the prior SPR biosensors, the proposed SPR biosensors would offer greater sensitivity in some cases, enough sensitivity to detect bioparticles having dimensions as small as nanometers. A surface plasmon wave can be described as a light-induced collective oscillation in electron density at the interface between a metal and a dielectric. At SPR, most incident photons are either absorbed or scattered at the metal/dielectric interface and, consequently, reflected light is greatly attenuated. The resonance wavelength and angle of incidence depend upon the permittivities of the metal and dielectric. An SPR sensor of the type most widely used heretofore includes a gold film coated with a ligand a substance that binds analyte molecules. The gold film is thin enough to support evanescent-wave coupling through its thickness. The change in the effective index of refraction at the surface, and thus the change in the SPR response, increases with the number of bound analyte molecules. The device is illuminated at a fixed wavelength, and the intensity of light reflected from the gold surface opposite the ligand-coated surface is measured as a function of the angle of incidence. From these measurements, the angle of minimum reflection intensity is determined

Organotellurium ligands – designing and complexation reactions

Indian Academy of Sciences (India)

Unknown

membered rings it is negative and ~30 ppm only. Keywords. Organotellurium ligands; hybrid telluroether; platinum metal complexes; tellurium-125 NMR. 1. Introduction. Tellurium is the noblest metalloid which may act as a Lewis acid as well as Lewis base. The ligand chemistry of tellurium, which acts as a 'soft' donor, was ...

Preparation, Spectroscopic Investigation and Biological Activity of New Mixed Ligand Chelates

International Nuclear Information System (INIS)

Alassbaly, F.S.; Ajaily, M.M.E.

2014-01-01

Preparation and investigation of new Co(II), Ni(II), Zn(II) and Cr(III) chelates with mixed ligands including Schiff base (L1) formed from the condensation of 4-dimethylaminobenzaldehyde with 2-aminophenol and anthranilic acid (L2) were studied. The obtained Schiff base and mixed ligand chelates were subjected to several physiochemical techniques, in terms of CHN elemental analyses, molar conductivity, magnetic moment measurements, infrared, proton nuclear magnetic resonance, electronic and mass spectra. The analytical data showed the formation of the Schiff base compound and the ratio of metal to ligands of the chelates are 1:1:1(M:L1:L2). The infrared spectral data exhibited that the used ligands behaving as bidentate ligands towards the metal ions. The proton nuclear magnetic resonance spectral data showed the signals of the active groups in the ligands which entered in chelation with Zn(II) metal ion. The electronic spectral results showed the existence of pie (phenyl ring) and n = pie (C=N) of the ligands and suggested the geometrical structures of the chelates. Meanwhile, the mass spectral data revealed the fragmentations of the Schiff base, anthranilic acid and their Ni(II) mixed ligand chelate has been preformed the only chelate conducted for justification. All the prepared mixed chelates were non-electrolyte in nature. The antibacterial activity of the Schiff base, anthranilic acid, metal salts and mixed ligand chelates were studied and found to be that mixed ligand chelates have the most biological activity in comparison to the free ligands and salts. (author)

Free-energy relationships in ion channels activated by voltage and ligand

Science.gov (United States)

Chowdhury, Sandipan

2013-01-01

Many ion channels are modulated by multiple stimuli, which allow them to integrate a variety of cellular signals and precisely respond to physiological needs. Understanding how these different signaling pathways interact has been a challenge in part because of the complexity of underlying models. In this study, we analyzed the energetic relationships in polymodal ion channels using linkage principles. We first show that in proteins dually modulated by voltage and ligand, the net free-energy change can be obtained by measuring the charge-voltage (Q-V) relationship in zero ligand condition and the ligand binding curve at highly depolarizing membrane voltages. Next, we show that the voltage-dependent changes in ligand occupancy of the protein can be directly obtained by measuring the Q-V curves at multiple ligand concentrations. When a single reference ligand binding curve is available, this relationship allows us to reconstruct ligand binding curves at different voltages. More significantly, we establish that the shift of the Q-V curve between zero and saturating ligand concentration is a direct estimate of the interaction energy between the ligand- and voltage-dependent pathway. These free-energy relationships were tested by numerical simulations of a detailed gating model of the BK channel. Furthermore, as a proof of principle, we estimate the interaction energy between the ligand binding and voltage-dependent pathways for HCN2 channels whose ligand binding curves at various voltages are available. These emerging principles will be useful for high-throughput mutagenesis studies aimed at identifying interaction pathways between various regulatory domains in a polymodal ion channel. PMID:23250866

Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression

Science.gov (United States)

Pi, Fengmei; Binzel, Daniel W.; Lee, Tae Jin; Li, Zhefeng; Sun, Meiyan; Rychahou, Piotr; Li, Hui; Haque, Farzin; Wang, Shaoying; Croce, Carlo M.; Guo, Bin; Evers, B. Mark; Guo, Peixuan

2018-01-01

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for specific targeting and extracellular vesicles for efficient membrane fusion, the resulting ligand-displaying extracellular vesicles were capable of specific delivery of siRNA to cells, and efficiently blocked tumour growth in three cancer models. Extracellular vesicles displaying an aptamer that binds to prostate-specific membrane antigen, and loaded with survivin siRNA, inhibited prostate cancer xenograft. The same extracellular vesicle instead displaying epidermal growth-factor receptor aptamer inhibited orthotopic breast cancer models. Likewise, survivin siRNA-loaded and folate-displaying extracellular vesicles inhibited patient-derived colorectal cancer xenograft.

Identification and characterization of PPARα ligands in the hippocampus.

Science.gov (United States)

Roy, Avik; Kundu, Madhuchhanda; Jana, Malabendu; Mishra, Rama K; Yung, Yeni; Luan, Chi-Hao; Gonzalez, Frank J; Pahan, Kalipada

2016-12-01

Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPARα. Site-directed mutagenesis studies further revealed that PPARα Y464 and Y314 are involved in binding these hippocampal ligands. Moreover, these ligands activated PPARα and upregulated the synaptic function of hippocampal neurons. These results highlight the discovery of hippocampal ligands of PPARα capable of modulating synaptic functions.

Ligand-assisted fabrication, structure, and luminescence properties of Fe:ZnSe quantum dots

International Nuclear Information System (INIS)

Xie, Ruishi; Zhang, Xingquan; Liu, Haifeng

2014-01-01

Highlights: • A green route is developed for synthesis of water-soluble and fluorescent Fe:ZnSe quantum dots. • Tunable luminescence intensity can be realized with different ligand-to-Zn molar ratios. • The obtained quantum dots are in the so-called “quantum confinement regime”. -- Abstract: Here, we report a synthetic route for highly emissive Fe:ZnSe quantum dots in aqueous media using the mercaptoacetic acid ligand as stabilizing agent. The structural, morphological, componential, and optical properties of the resulting quantum dots were explored by the X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray spectroscopy, inductively coupled plasma mass spectrometry, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, photoluminescence and UV–visible absorption spectroscopies. The average crystallite size was calculated to be about ca., 4.0 nm using the Scherrer equation, which correlates well with the value obtained from the transmission electron microscopy analysis. The obtained water-soluble Fe:ZnSe quantum dots in the so-called “quantum confinement regime” are spherical shaped, possess the cubic sphalerite crystal structure, and exhibit tunable luminescence properties. The presence of mercaptoacetic acid on the surface of Fe:ZnSe quantum dots was confirmed by the Fourier transform infrared spectroscopy measurements. As the ligand/Zn molar ratio increases from 1.3 to 2.8, there is little shift in the absorption peak of the Fe:ZnSe sample, indicating that the particle size of the obtained quantum dots is not changed during the synthetic process. The photoluminescence quantum yield of the as-prepared water-soluble Fe:ZnSe quantum dots can be up to 39%. The molar ratio of ligand-to-Zn plays a crucial role in determining the final luminescence properties of the resulting quantum dots, and the maximum PL intensity appears as the ligand-to-Zn molar ratio is 2.2. In addition, the underlying mechanism for

Ligand-assisted fabrication, structure, and luminescence properties of Fe:ZnSe quantum dots

Energy Technology Data Exchange (ETDEWEB)

Xie, Ruishi, E-mail: rxie@foxmail.com; Zhang, Xingquan; Liu, Haifeng

2014-03-15

Highlights: • A green route is developed for synthesis of water-soluble and fluorescent Fe:ZnSe quantum dots. • Tunable luminescence intensity can be realized with different ligand-to-Zn molar ratios. • The obtained quantum dots are in the so-called “quantum confinement regime”. -- Abstract: Here, we report a synthetic route for highly emissive Fe:ZnSe quantum dots in aqueous media using the mercaptoacetic acid ligand as stabilizing agent. The structural, morphological, componential, and optical properties of the resulting quantum dots were explored by the X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray spectroscopy, inductively coupled plasma mass spectrometry, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, photoluminescence and UV–visible absorption spectroscopies. The average crystallite size was calculated to be about ca., 4.0 nm using the Scherrer equation, which correlates well with the value obtained from the transmission electron microscopy analysis. The obtained water-soluble Fe:ZnSe quantum dots in the so-called “quantum confinement regime” are spherical shaped, possess the cubic sphalerite crystal structure, and exhibit tunable luminescence properties. The presence of mercaptoacetic acid on the surface of Fe:ZnSe quantum dots was confirmed by the Fourier transform infrared spectroscopy measurements. As the ligand/Zn molar ratio increases from 1.3 to 2.8, there is little shift in the absorption peak of the Fe:ZnSe sample, indicating that the particle size of the obtained quantum dots is not changed during the synthetic process. The photoluminescence quantum yield of the as-prepared water-soluble Fe:ZnSe quantum dots can be up to 39%. The molar ratio of ligand-to-Zn plays a crucial role in determining the final luminescence properties of the resulting quantum dots, and the maximum PL intensity appears as the ligand-to-Zn molar ratio is 2.2. In addition, the underlying mechanism for

Using chemical shift perturbation to characterise ligand binding.

Science.gov (United States)

Williamson, Mike P

2013-08-01

Chemical shift perturbation (CSP, chemical shift mapping or complexation-induced changes in chemical shift, CIS) follows changes in the chemical shifts of a protein when a ligand is added, and uses these to determine the location of the binding site, the affinity of the ligand, and/or possibly the structure of the complex. A key factor in determining the appearance of spectra during a titration is the exchange rate between free and bound, or more specifically the off-rate koff. When koff is greater than the chemical shift difference between free and bound, which typically equates to an affinity Kd weaker than about 3μM, then exchange is fast on the chemical shift timescale. Under these circumstances, the observed shift is the population-weighted average of free and bound, which allows Kd to be determined from measurement of peak positions, provided the measurements are made appropriately. (1)H shifts are influenced to a large extent by through-space interactions, whereas (13)Cα and (13)Cβ shifts are influenced more by through-bond effects. (15)N and (13)C' shifts are influenced both by through-bond and by through-space (hydrogen bonding) interactions. For determining the location of a bound ligand on the basis of shift change, the most appropriate method is therefore usually to measure (15)N HSQC spectra, calculate the geometrical distance moved by the peak, weighting (15)N shifts by a factor of about 0.14 compared to (1)H shifts, and select those residues for which the weighted shift change is larger than the standard deviation of the shift for all residues. Other methods are discussed, in particular the measurement of (13)CH3 signals. Slow to intermediate exchange rates lead to line broadening, and make Kd values very difficult to obtain. There is no good way to distinguish changes in chemical shift due to direct binding of the ligand from changes in chemical shift due to allosteric change. Ligand binding at multiple sites can often be characterised, by

Chemical modification of protein a chromatography ligands with polyethylene glycol. II: Effects on resin robustness and process selectivity.

Science.gov (United States)

Weinberg, Justin; Zhang, Shaojie; Kirkby, Allison; Shachar, Enosh; Carta, Giorgio; Przybycien, Todd

2018-04-20

We have proposed chemical modification of Protein A (ProA) chromatography ligands with polyethylene glycol (PEGylation) as a strategy to increase the resin selectivity and robustness by providing the ligand with a steric repulsion barrier against non-specific binding. Here, we report on robustness and selectivity benefits for Repligen CaptivA PriMAB resin with ligands modified with 5.2 kDa and 21.5 kDa PEG chains, respectively. PEGylation of ProA ligands allowed the resin to retain a higher percentage of static binding capacity relative to the unmodified resin upon digestion with chymotrypsin, a representative serine protease. The level of protection against digestion was independent of the PEG molecular weight or modification extent for the PEGylation chemistry used. Additionally, PEGylation of the ligands was found to decrease the level of non-specific binding of fluorescently labeled bovine serum albumin (BSA) aggregates to the surface of the resin particles as visualized via confocal laser scanning microscopy (CLSM). The level of aggregate binding decreased as the PEG molecular weight increased, but increasing the extent of modification with 5.2 kDa PEG chains had no effect. Further examination of resin particles via CLSM confirmed that the PEG chains on the modified ligands were capable of blocking the "hitchhiking" association of BSA, a mock contaminant, to an adsorbed mAb that is prone to BSA binding. Ligands modified with 21.5 kDa PEG chains were effective at blocking the association, while ligands modified with 5.2 kDa PEG chains were not. Finally, ligands with 21.5 kDa PEG chains increased the selectivity of the resin against host cell proteins (HCPs) produced by Chinese Hamster Ovary (CHO) cells by up to 37% during purification of a monoclonal antibody (mAb) from harvested cell culture fluid (HCCF) using a standard ProA chromatography protocol. The combined work suggests that PEGylating ProA chromatography media is a viable pathway for

Evaluating e-Government and Good Governance Correlation

Directory of Open Access Journals (Sweden)

Suhardi Suhardi

2016-03-01

Full Text Available Assessing the achievement of Indonesian government institutions in implementing e-government has been conducted since around a decade ago. Several national assessments are available with almost the same ranking results. There is an agreement that the ultimate goal of e-government implementation is to achieve good government governance (GGG, while success stories of e-government require good governance practices. This study explored the correlation between e-government achievement and GGG achievement in Indonesia. Spearman’s rank correlation was used to characterize the relationship strength between e-government assessment results and good governance assessment results. The data were collected from institutions that participated in e-government and good governance assessments. The results showed that the correlation between these two entities is not very strong. Most cases showed that e-government implementation and the achievement of good governance have only a moderate positive correlation and none of the studied cases indicated a significant connection. This result can be attributed to the lack of emphasis on goals achievement in the assessments. Thus, it is recommended that future Indonesian e-government assessments should involve impact indicators.