38229-72-0Relevant 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 (2018/10/24)
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 of a trisaccharide related to the cytotoxic triterpenoid saponins isolated from the bark of Albizia procera
Liu, Qing-Chao,Guo, Tian-Tian,Zhao, Cong,Sun, Jing,Li, Wen-Hong
, p. 361 - 368 (2014/04/03)
Chemical synthesis of a trisaccharide related to the cytotoxic triterpenoid saponins isolated from the bark of Albizia procera has been accomplished through a concise stepwise glycosylation strategy starting from commercially available D-xylose, 2-acetamido-2-deoxy-D-glucose and L-arabinose. The target trisaccharide was designed with a 4-methoxyphenyl (MP) aglycone to extend the scope of conversion to suitable glycoconjugates via selective removal of 4-methoxyphenyl (MP) group. An unexpected phenomenon, i.e., the arabinosyl residue assumed the 1C4 conformation instead of the typical 4C1 form, was observed. Deprotection could restore the normal conformation. Copyright
Synthesis and conformational analysis of glycomimetic analogs of thiochitobiose
Fettke, Anja,Peikow, Dirk,Peter, Martin G.,Kleinpeter, Erich
supporting information; experimental part, p. 4356 - 4366 (2009/10/09)
The synthesis of six analogs of N,N′-diacetylchitobiose is reported, including a novel transglycosylation reaction for the preparation of S-aryl thioglycosides. The conformations of the compounds were studied by a combination of NMR spectroscopy and molec
Probing synergy between two catalytic strategies in the glycoside hydrolase O-GlcNAcase using multiple linear free energy relationships
Greig, Ian R.,Macauley, Matthew S.,Williams, Ian H.,Vocadlo, David J.
supporting information; experimental part, p. 13415 - 13422 (2010/01/16)
Human O-GlcNAcase plays an important role in regulating the post-translational modification of serine and threonine residues with β-O-linked N-acetylglucosamine monosaccharide unit (O-GlcNAc). The mechanism of O-GlcNAcase involves nucleophilic participation of the 2-acetamido group of the substrate to displace a glycosidically linked leaving group. The tolerance of this enzyme for variation in substrate structure has enabled us to characterize O-GlcNAcase transition states using several series of substrates to generate multiple simultaneous free-energy relationships. Patterns revealing changes in mechanism, transition state, and rate-determining step upon concomitant variation of both nucleophilic strength and leaving group abilities are observed. The observed changes in mechanism reflect the roles played by the enzymic general acid and the catalytic nucleophile. Significantly, these results illustrate how the enzyme synergistically harnesses both modes of catalysis; a feature that eludes many small molecule models of catalysis. These studies also suggest the kinetic significance of an oxocarbenium ion intermediate in the O-GlcNAcase-catalyzed hydrolysis of glucosaminides, probing the limits of what may be learned using nonatomistic investigations of enzymic transition-state structure and offering general insights into how the superfamily of retaining glycoside hydrolases act as efficient catalysts.
N-Dimethylphosphoryl-protection in the efficient synthesis of glucosamine-containing oligosaccharides with alternate N-acyl substitutions
Yang, You,Yu, Biao
, p. 7049 - 7052 (2008/03/12)
Ready transformation of N-dimethylphosphoryl-protection into the corresponding N-acyl derivatives (in the presence of acyl chlorides and DMAP in pyridine) provided an effective approach to the synthesis of glucosamine-containing oligosaccharides with alte
A phase-transfer glucosamination of phenols catalyzed by polyethylene glycol
Kur'yanov,Priskoka,Chupakhina,Chirva
, p. 300 - 301 (2008/02/02)
Glycosylation of phenols with α-D-glucosaminyl chloride peracetate catalyzed by polyethylene glycol (PEG) was carried out in a solid-liquid phase transfer system at room temperature. The results were compared with those previously obtained for the catalys
Aromatic crown ethers as phase transfer catalysts in the synthesis of N-acetylglucosamine β-aryl glycosides
Chupakhina,Kur'yanov,Chirva,Grigorash,Kotlyar,Kamalov
, p. 301 - 303 (2007/10/03)
The crown ether-catalyzed glycosylation of phenol, 4-methoxyphenol, and 4-nitrophenol was studied under phase transfer conditions in solid-liquid system. The asymmetric dibenzocrown esters are superior to [3.3]dibenzo-18- crown-6 and 15-crown-5 in the cat
Synthesis of N-Acetylglucosamine Aryl β-Glycosides Catalyzed by Crown Compounds
Kur'yanov,Chupakhina,Zemlyakov,Kotlyar,Kamalov,Chirva
, p. 385 - 389 (2007/10/03)
Glycosylation of various phenols with α-D-glucosaminyl chloride peracetate in a solid phase-liquid system catalyzed by crown compounds was studied. The highest yields of aryl β-glycosides were observed at room temperature in acetonitrile using anhydrous p
Use of dichlorophthaloyl (DCPhth) group as an amino protecting group in oligosaccharide synthesis
Lergenmueller, Matthias,Ito, Yukishige,Ogawa, Tomoya
, p. 1381 - 1394 (2007/10/03)
As an alternative to phthaloyl (Phth) group, 4,5-dichlorophthaloyl (DCPhth) group was investigated as an amino protecting group to prove it to be useful for the synthesis of β-glycosides of 2-acetamido-2-deoxy glucose (GlcNAc). DCPhth was introduced onto the C-2 nitrogen of glucosamine to give 2, which was further transformed into mono- and di- and trisaccharide derivatives which constitute basic structural units of asparagine linked glycoprotein oligosaccharides. DCPhth group proved to have sufficient stability under the standard conditions of protecting group manipulations (e.g. deacetylation, benzylation, benzylidenation), and Lewis acid-, silver salt- and iodonium ion-promoted glycosylation. Removal of DCPhth group was smoothly performed by using ethylenediamine in alcoholic solvent under substantially milder conditions required for deprotection of Phth.
Stereospecific Synthesis of Aryl β-D-N-Acetylglucopyranosides by Phase Transfer Catalysis
Roy, Rene,Tropper, Francois
, p. 2097 - 2102 (2007/10/02)
Under phase transfer catalyzed conditions, 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl chloride (1) reacts with a series of phenoxides to afford high yields of acetylated aryl β-D-N-acetylglucopyranosides (3-8).Deprotection of the hydroxyl g
