190181-66-9Relevant academic research and scientific papers
Thioglycosides Are Efficient Metabolic Decoys of Glycosylation that Reduce Selectin Dependent Leukocyte Adhesion
Wang, Shuen-Shiuan,Gao, Xuefeng,Solar, Virginia del,Yu, Xinheng,Antonopoulos, Aristotelis,Friedman, Alan E.,Matich, Eryn K.,Atilla-Gokcumen, G. Ekin,Nasirikenari, Mehrab,Lau, Joseph T.,Dell, Anne,Haslam, Stuart M.,Laine, Roger A.,Matta, Khushi L.,Neelamegham, Sriram
, p. 1519 - 5,1532 (2018)
Small-molecule inhibitors of glycosylation can be applied in basic science studies, and clinical investigations as anti-inflammatory, anti-metastatic, and anti-viral therapies. This article demonstrates that thioglycosides represent a class of potent metabolic decoys that resist hydrolysis, and block E-selectin-dependent leukocyte adhesion in models of inflammation. Metabolic decoys are synthetic analogs of naturally occurring biosynthetic acceptors. These compounds divert cellular biosynthetic pathways by acting as artificial substrates that usurp the activity of natural enzymes. While O-linked glycosides are common, they are only partially effective even at millimolar concentrations. In contrast, we report that N-acetylglucosamine (GlcNAc) incorporated into various thioglycosides robustly truncate cell surface N- and O-linked glycan biosynthesis at 10–100 μM concentrations. The >10-fold greater inhibition is in part due to the resistance of thioglycosides to hydrolysis by intracellular hexosaminidases. The thioglycosides reduce β-galactose incorporation into lactosamine chains, cell surface sialyl Lewis-X expression, and leukocyte rolling on selectin substrates including inflamed endothelial cells under fluid shear. Treatment of granulocytes with thioglycosides prior to infusion into mouse inhibited neutrophil homing to sites of acute inflammation and bone marrow by ～80%–90%. Overall, thioglycosides represent an easy to synthesize class of efficient metabolic inhibitors or decoys. They reduce N-/O-linked glycan biosynthesis and inflammatory leukocyte accumulation.
Synthesis and glycan priming activity of acetylated disaccharides
Sarkar, Arun K,Brown, Jillian R,Esko, Jeffrey D
, p. 287 - 300 (2007/10/03)
Five disaccharides related in structure to the glycans of vertebrate mucins have been chemically synthesized using orthogonal blocking, coupling and deblocking techniques. These include 2-naphthylmethyl 3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-(1 → 4)-2-acetamido-3,6-di-O-acetyl-2-deoxy-β-D-glucopyranoside (6), 2-naphthylmethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl-(1 → 3)-2,4,6-tri-O-acetyl-β-D-galactopyranoside (14), 2-naphthylmethyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-(1 → 3)-2-acetamido-4,6-di-O-acetyl-2-deoxy-α-D-galactopyranoside (20), 2-naphthylmethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl-(1 → 3)-2-acetamido-4,6-di-O-acetyl-2-deoxy-α-D-galactopyranoside (23) and 2-naphthylmethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl-(1 → 6)-2-acetamido-3,4-di-O-acetyl-2-deoxy-α-D-galactopyranoside (27). These per-O-acetylated compounds were fed to U-937 cells to test their ability to prime oligosaccharide synthesis, inhibit glycoprotein biosynthesis and alter adhesion to E-selectin expressed on endothelial cells. The results show that 6, 14, and 20 served as substrates for oligosaccharide synthesis. The generation of glycoside-primed glycans altered the formation of glycoproteins on the cell surface and inhibited cell adhesion dependent on E-selectin. (C) 2000 Elsevier Science Ltd.
The synthesis of glycosides of 2-acetamido-2-deoxyglucose catalyzed by mercuric iodide
Zemlyakov,Kur'yanov,Sidorova,Chirva
, p. 551 - 558 (2007/10/03)
The glycosylation of various alcohols with peracetylated α-D-glucosaminyl chloride catalyzed with mercuric iodide was studied along with the dependence of the reaction course on temperature, solvent, and quantity of catalyst. At room temperature, only β-glycosides of peracetylated N-acetylglucosamine were shown to result in dichloroethane or nitromethane with high yields. At 90-95°C, anomerization was observed, which led to the corresponding α-glycosides. The possibility of the synthesis of disaccharides with the β1→6 bond catalyzed by mercuric iodide was demonstrated.
Synthesis of hydrophobic derivatives of muramyldipeptides
Zemlyakov,Kur'yanov,Tsikalov,Aksenova,Chirva
, p. 61 - 66 (2007/10/03)
Methyl esters of the cyclohexyl-, phenethyl-, (2-naphthyl)methyl-, and 2′-(1-naphthyl)ethyl β-glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine have been synthesized. The corresponding glycosides of N-acetylglucosamine were obtained by glycosylating the alcohols with the peracetate of α-glucosaminyl chloride in the presence of HgI2, followed by deacetylation. Subsequent benzylidenation and alkylation with α-L-chloropropionic acid led to glycosylmuramic acids, the condensation of which with the dipeptide and final debenzylidenation gave the desired glycopeptides.
Synthesis of β-glycosides of N-acetylglucosamine in the presence of HgI2
Zemlyakov,Kur'yanov,Chirva
, p. 352 - 355 (2007/10/03)
The use of HgI2 as catalyst in the synthesis of trans-glycosides of N-acetylglucosamine is described. Using this catalyst, β-glycosides of N-acetylglucosamine with aglycons of different structures and lyophilicities have been synthesized. The p
