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11.
Heparin-induced cancer cell death 总被引:5,自引:0,他引:5
Linhardt RJ 《Chemistry & biology》2004,11(4):420-422
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An oligopeptide modified on both the N- and C-termini with hydrophobic moieties was prepared on a solid phase and anchored into a liposome, stabilizing the fold of the peptide into a beta-hairpin, which would otherwise be a random coil. 相似文献
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Complex natural polysaccharides, glycosaminoglycans (GAGs), are a class of ubiquitous macromolecules that exhibit a wide range of biological functions and participate and regulate multiple cellular events and (patho)physiological processes. They are generally present either as free chains (hyaluronic acid and bacterial acidic polysaccharides) or as side chains of proteoglycans (PGs; chondroitin/dermatan sulfate, heparin/heparan sulfate, and keratan sulfate) and are most often found in cell membranes and in the extracellular matrix. The recent emergence of modern analytical tools for their study has produced a virtual explosion in the field of glycomics. CE, due to its high resolving power and sensitivity, has been useful in the analysis of intact GAGs and GAG-derived oligosaccharides and disaccharides affording concentration and structural characterization data essential for understanding the biological functions of GAGs. In this review, novel off-line and on-line CE-MS and MS/MS methods for screening of GAG-derived oligosaccharides and disaccharides will be discussed. 相似文献
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Zhang Z McCallum SA Xie J Nieto L Corzana F Jiménez-Barbero J Chen M Liu J Linhardt RJ 《Journal of the American Chemical Society》2008,130(39):12998-13007
We report the first chemoenzymatic synthesis of the stable isotope-enriched heparin from a uniformly labeled [(13)C,(15)N]N-acetylheparosan (-GlcA(1,4)GlcNAc-) prepared from E. coli K5. Glycosaminoglycan (GAG) precursors and heparin were formed from N-acetylheparosan by the following steps: chemical N-deacetylation and N-sulfonation leading to N-sulfoheparosan (-GlcA(1,4)GlcNS-); enzyme-catalyzed C5-epimerization and 2-O-sulfonation leading to undersulfated heparin (-IdoA2S(1,4)GlcNS-); enzymatic 6-O-sulfonation leading to the heparin backbone (-IdoA2S(1,4)GlcNS6S-); and selective enzymatic 3-O-sulfonation leading to the anticoagulant heparin, containing the GlcNS6S3S residue. Heteronuclear, multidimensional nuclear magnetic resonance spectroscopy was employed to analyze the chemical composition and solution structure of [(13)C,(15)N]N-acetylheparosan, precursors, and heparin. Isotopic enrichment was found to provide well-resolved (13)C spectra with the high sensitivity required for conformational studies of these biomolecules. Stable isotope-labeled heparin was indistinguishable from heparin derived from animal tissues and is a novel reagent for studying the interaction of heparin with proteins. 相似文献
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Escherichia coli K5 heparosan was enzymatically modified by Chen and colleagues to construct a library of heparan sulfate polysaccharides for evaluation, leading to the discovery that a 2-O-sulfoiduronic acid residue is not essential for antithrombin-mediated anticoagulant activity in larger oligosaccharide and polysaccharide structures. 相似文献
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Kumar A Pushparaj VL Murugesan S Viswanathan G Nalamasu R Linhardt RJ Nalamasu O Ajayan PM 《Langmuir : the ACS journal of surfaces and colloids》2006,22(21):8631-8634
We demonstrate the one-step synthesis of a silica-gold nanocomposite by simultaneous hydrolysis and reduction of gold chloride. The aminophenyl group was used as a reducing agent, and the trimethoxy silane group acts a precursor for the formation of silica. The porous gold nanoparticles were formed by etching out the silica-gold nanocomposite by hydrofluoric acid. The electron diffraction of porous gold nanoparticles showed that the particle are polycrystalline with FCC structure. The silica-gold nanocomposite exhibited nonlinear current-voltage behavior, and the porous gold nanoparticles displayed linear current-voltage behavior. 相似文献
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Recent advances in sulfotransferase enzyme activity assays 总被引:1,自引:0,他引:1
Paul P Suwan J Liu J Dordick JS Linhardt RJ 《Analytical and bioanalytical chemistry》2012,403(6):1491-1500
Sulfotransferases are enzymes that catalyze the transfer of sulfo groups from a donor, for example 3'-phosphoadenosine 5'-phosphosulfate, to an acceptor, for example the amino or hydroxyl groups of a small molecule, xenobiotic, carbohydrate, or peptide. These enzymes are important targets in the design of novel therapeutics for treatment of a variety of diseases. This review examines assays used for this important class of enzyme, paying particular attention to sulfotransferases acting on carbohydrates and peptides and the major challenges associated with their analysis. 相似文献
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Masuko S Bera S Green DE Weïwer M Liu J DeAngelis PL Linhardt RJ 《The Journal of organic chemistry》2012,77(3):1449-1456
Eight N-acetylglucosamine-1-phosphate and N-acetylgalactosamine-1-phosphate analogs have been synthesized chemically and were tested for their recognition by the GlmU uridyltransferase enzyme. Among these, only substrates that have an amide linkage to the C-2 nitrogen were transferred by GlmU to afford their corresponding uridine diphosphate(UDP)-sugar nucleotides. Resin-immobilized GlmU showed comparable activity to nonimmobilized GlmU and provides a more facile final step in the synthesis of an unnatural UDP-donor. The synthesized unnatural UDP-donors were tested for their activity as substrates for glycosyltransferases in the preparation of unnatural glycosaminoglycans in vitro. A subset of these analogs was useful as donors, increasing the synthetic repertoire for these medically important polysaccharides. 相似文献