Chapter 10: Enzymatic thioglycosylation: current knowledge and challenges
Published:20 Mar 2014
L. Guillotin, P. Lafite, and R. Daniellou, in Carbohydrate Chemistry: Chemical and Biological Approaches, Volume 40, ed. A. Pilar Rauter, T. Lindhorst, and Y. Queneau, The Royal Society of Chemistry, 2014, vol. 40, ch. 10, pp. 178-194.
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Carbohydrates play an important part in a vast array of biological processes and therefore glycomimetics are currently becoming a powerful class of novel therapeutics.1 Amongst them, thioglycosides, in which a sulfur atom has replaced the glycosidic oxygen atom, are tolerated by most biological systems. Their major advantages rely on the fact that they adopt similar conformations than the corresponding O-glycosides and especially that they prove to be less sensitive to acid/base or enzyme-mediated hydrolysis. Such compounds have already demonstrated to be valuable tools as good chemical donors for synthetic purposes,2,3 as stable intermediates in X-ray crystallographic analysis of proteins4 and, of particular interest, as competitive inhibitors of a wide range of glycosidases (or glycoside hydrolases, GH) involved in numerous diseases.5 Besides the synthetic methodologies developed throughout the years by organic chemists, the presence of natural S-glycosylconjugates was recently assessed and led to the discovery of the enzymes involved in such rare biocatalytic processes. In parallel, the increase of knowledge on the mechanism and the structure of glycosidases has conducted to the development of original catalyst with greatly improved synthetic properties for thioglycosidic linkages.