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Potential Ligands (potential + ligand)
Selected AbstractsCell surface nucleolin on developing muscle is a potential ligand for the axonal receptor protein tyrosine phosphatase-,FEBS JOURNAL, Issue 20 2006Daniel E. Alete Reversible tyrosine phosphorylation, catalyzed by receptor tyrosine kinases and receptor tyrosine phosphatases, plays an essential part in cell signaling during axonal development. Receptor protein tyrosine phosphatase-, has been implicated in the growth, guidance and repair of retinal axons. This phosphatase has also been implicated in motor axon growth and innervation. Insect orthologs of receptor protein tyrosine phosphatase-, are also implicated in the recognition of muscle target cells. A potential extracellular ligand for vertebrate receptor protein tyrosine phosphatase-, has been previously localized in developing skeletal muscle. The identity of this muscle ligand is currently unknown, but it appears to be unrelated to the heparan sulfate ligands of receptor protein tyrosine phosphatase-,. In this study, we have used affinity chromatography and tandem MS to identify nucleolin as a binding partner for receptor protein tyrosine phosphatase-, in skeletal muscle tissue. Nucleolin, both from tissue lysates and in purified form, binds to receptor protein tyrosine phosphatase-, ectodomains. Its expression pattern also overlaps with that of the receptor protein tyrosine phosphatase-,-binding partner previously localized in muscle, and nucleolin can also be found in retinal basement membranes. We demonstrate that a significant amount of muscle-associated nucleolin is present on the cell surface of developing myotubes, and that two nucleolin-binding components, lactoferrin and the HB-19 peptide, can block the interaction of receptor protein tyrosine phosphatase-, ectodomains with muscle and retinal basement membranes in tissue sections. These data suggest that muscle cell surface-associated nucleolin represents at least part of the muscle binding site for axonal receptor protein tyrosine phosphatase-, and that nucleolin may also be a necessary component of basement membrane binding sites of receptor protein tyrosine phosphatase-,. [source] Competition STD NMR for the detection of high-affinity ligands and NMR-based screeningMAGNETIC RESONANCE IN CHEMISTRY, Issue 6 2004Yu-Sen Wang Abstract The reported competition STD NMR method combines saturation transfer difference (STD) NMR with competition binding experiments to allow the detection of high-affinity ligands that undergo slow chemical exchange on the NMR time-scale. With this technique, the presence of a competing high-affinity ligand in the compound mixture can be detected by the disappearance or reduction of the STD signals of a low-affinity indicator ligand. This is demonstrated on a BACE1 (,-site amyloid precursor protein cleaving enzyme 1) protein,inhibitor system. This method can also be used to derive an approximate value, or a lower limit, for the dissociation constant of the potential ligand based on the reduction of the signal intensity of the STD indicator, which is illustrated on an HSA (human serum albumin) model system. This leads to important applications of the competition STD NMR method for lead discovery: it can be used (i) for compound library screening against a broad range of drug targets to identify both high- and low-affinity ligands and (ii) to rank order analogs rapidly and derive structure,activity relationships, which are used to optimize these NMR hits into viable drug leads. Copyright © 2004 John Wiley & Sons, Ltd. [source] Synthesis of Amino-Bridged Oligosaccharide MimeticsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2010Janna Neumann Abstract Synthesis of amino-bridged oligosaccharides using reductive amination opens rapid access to novel glycomimetic target structures as potential ligands for the receptor protein NKR P1 of natural killer cells. Emphasis was laid on fast and facile synthetic routes. The carbonyl building blocks were easily obtained by oxidation with Dess,Martin periodinane or iodoxybenzoic acid (IBX). For the required amino-functionalized units, reduction of azide precursors was advantageous, and generation of the novel oligosaccharides was achieved by subsequent reductive amination. The target saccharide structures feature a bridging nitrogen atom inserted between two non-anomeric positions as well as including one anomeric position. [source] Towards the Synthesis of Highly Functionalized Chiral ,-Amino Nitriles by Aminative Cyanation and Their Synthetic ApplicationsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 1 2006Luca Bernardi Abstract The cyanobis(dibenzylamino)borane-mediated transformation of chiral aldehydes into the corresponding ,-amino nitriles is described. Starting from these compounds short synthetic routes can be envisaged for obtaining diastereomerically pure functionalized 1,2-diamines and hydroxylated ,-amino acids that are of interest as core key units of biologically active substances or as potential ligands for asymmetric catalysis. The stereochemical outcome of the aminative cyanation reaction is discussed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Preparation, characterization and biological evaluation of 99mTc(CO)3 -labelled cyclic polyaminesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2005H. P. Vanbilloen Abstract Three cyclic polyamines, namely 1,4,7-triazacyclononane, 1,4,7,10-tetraazacyclo-dodecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam), were evaluated as potential ligands for complexation of a technetium(I) tricarbonyl core. They can be used as bifunctional chelating agents for labelling bioactive compounds. Each of the three ligands forms a positively charged technetium tricarbonyl complex in high yield but heating is required to promote complex formation. The charge of the 99mTc(I)tricarbonyl labelled derivatives was confirmed using electrophoresis, and radio-LC,MS supports their proposed chemical identity. After i.v. injection in mice, the compounds were rapidly cleared from the blood by the hepatobiliary or urinary pathway depending on their lipophilicity. Copyright © 2005 John Wiley & Sons, Ltd. [source] Using nondenaturing mass spectrometry to detect fortuitous ligands in orphan nuclear receptorsPROTEIN SCIENCE, Issue 4 2003Noelle Potier Abstract Nondenaturing electrospray mass spectrometry (ESI-MS) has been used to reveal the presence of potential ligands in the ligand-binding domain (LBD) of orphan nuclear receptors. This new approach, based on supramolecular mass spectrometry, allowed the detection and identification of fortuitous ligands for the retinoic acid-related orphan receptor , (ROR,) and the ultraspiracle protein (USP). These fortuitous ligands were specifically captured from the host cell with the proper stoichiometry. After organic extraction, these molecules have been characterized by classic analytical methods and identified as stearic acid for ROR, and a phosphatidylethanolamine (PE) for USP, as confirmed by crystallography. These molecules act as "fillers" and may not be the physiological ligands, but they prove to be essential to stabilize the active conformation of the LBD, enabling its crystallization. The resulting crystal structures provide a detailed picture of the ligand-binding pocket, allowing the design of highly specific synthetic ligands that can be used to characterize the function of orphan nuclear receptors. An additional advantage of this new method is that it is not based on a functional test and that it can detect low-affinity ligands. [source] gem -Dimethylcyclopropanation of dibenzylideneacetone using triisopropyl sulfoxonium tetrafluoroborateACTA CRYSTALLOGRAPHICA SECTION C, Issue 2 2009Michael G. Edwards The reaction between dibenzylideneacetone (dba) and triisopropyl sulfoxonium tetrafluoroborate has been reinvestigated. The stereochemistry of the major diasteromeric bis(gem -dimethylcyclopropane) adduct has now been assigned as [(1RS,3RS)-2,2-dimethyl-3-phenylcyclopropyl][(1SR,3SR)-2,2-dimethyl-3-phenylcyclopropyl]methanone, C23H26O, by X-ray crystallographic studies on a twinned crystal. The asymmetric unit contains two molecules of the adduct, the conformations of which differ in the orientation of the phenyl ring relative to the adjacent cyclopropanated double bond. The carbonyl groups of each adduct are aligned approximately along the a axis and in opposite directions to each other. The molecules pack to give a sinusoidal pattern along the b axis. This is the first acyclic bis(dimethylcyclopropyl) ketone for which an X-ray crystal structure determination has been reported, and is also the first bis-cyclopropanated dba analogue. The knowledge that the major diastereomer has the meso structure (and therefore the confirmation that the minor isomer is the racemate) will prove invaluable in future studies to utilize bis(dimethylcyclopropyl) ketones as reagents, in rearrangement processes, and as potential ligands and ligand precursors in organometallic chemistry. [source] N -Acyl amino acids and N -acyl neurotransmitter conjugates: neuromodulators and probes for new drug targetsBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2010Mark Connor The myriad functions of lipids as signalling molecules is one of the most interesting fields in contemporary pharmacology, with a host of compounds recognized as mediators of communication within and between cells. The N -acyl conjugates of amino acids and neurotransmitters (NAANs) have recently come to prominence because of their potential roles in the nervous system, vasculature and the immune system. NAAN are compounds such as glycine, GABA or dopamine conjugated with long chain fatty acids. More than 70 endogenous NAAN have been reported although their physiological role remains uncertain, with various NAAN interacting with a low affinity at G protein coupled receptors (GPCR) and ion channels. Regardless of their potential physiological function, NAAN are of great interest to pharmacologists because of their potential as flexible tools to probe new sites on GPCRs, transporters and ion channels. NAANs are amphipathic molecules, with a wide variety of potential fatty acid and headgroup moieties, a combination which provides a rich source of potential ligands engaging novel binding sites and mechanisms for modulation of membrane proteins such as GPCRs, ion channels and transporters. The unique actions of subsets of NAAN on voltage-gated calcium channels and glycine transporters indicate that the wide variety of NAAN may provide a readily exploitable resource for defining new pharmacological targets. Investigation of the physiological roles and pharmacological potential of these simple lipid conjugates is in its infancy, and we believe that there is much to be learnt from their careful study. [source] Synthesis, Cruzain Docking, and in,vitro Studies of Aryl-4-Oxothiazolylhydrazones Against Trypanosoma cruziCHEMMEDCHEM, Issue 9 2007Cristina, Lima Leite Prof. Abstract Research in recent years has demonstrated that the Trypanosoma cruzi cysteine protease cruzain (TCC) is a valid chemotherapeutic target. Herein we describe a small library of aryl-4-oxothiazolylhydrazones that have been tested in assays against T.,cruzi cell cultures. The docking studies carried out suggest that these compounds are potential ligands for the TCC enzyme. The most promising compound of this series, N -(4-oxo-5-ethyl-2,-thiazolin-2-yl)- N,-phenylthio-(Z)-ethylidenehydrazone (6,f), was shown to be very active at non-cytotoxic concentrations in in,vitro assays with mammalian cells and has a potency comparable with reference drugs such as nifurtimox (Nfx) and benznidazole (Bdz). [source] Chemoenzymatic synthesis and properties of Schiff bases containing (R)-1-(9-anthryl)ethylamineCHIRALITY, Issue 8 2002Marin Roje Abstract Racemic 1-(9-anthryl)ethylamine (10), obtained in 70% overall yield from commercial 9-cyanoanthracene, was kinetically resolved by the Candida antarctica A lipase-catalyzed acetylation with isopropyl acetate as acyl donor, affording (R)-(+)- 10 with 95.8% enantiomeric excess (e.e.) (E- value 43.5), which afforded Schiff bases (R)- 4 and(R)- 8.1H-NMR, CD, and MM2 calculations offer a consistent picture of the conformational properties of these potential ligands and an explanation for the limited enhancement of enantioselectivity in cyclopropanation of styrene by their Cu(I) complexes, as compared with previously studied ligands in this series. Chirality 14:625,631, 2002. © 2002 Wiley-Liss, Inc. [source] | ||||||||||