Thioglycoligase‐Based Assembly of Thiodisaccharides: Screening as β‐Galactosidase Inhibitors

Kim, Young-Wan; Chen, Hongming; Kim, Jin Hyo; Müllegger, Johannes; Mahuran, Don J.; Withers, Stephen G.

doi:10.1002/cbic.200700263

Cited by 36 publications

(22 citation statements)

References 47 publications

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“…In this context, Withers and co-workers accomplished the synthesis of thioglycosides as non cleavable substrate analogues designed for the inhibition of glycosidases and carbohydrate-binding proteins. 124 In particular, a small library of galactosyl thioglycosides 228-230 was accessed by coupling 2,4-dinitrophenyl b-D-galactopyranoside (226) with thiol-containing carbohydrates of D-gluco and D-galacto configurations (227); such reaction was promoted by a thioglycoligase derived from the Xanthomonas manihotis b-galactosidase (BgaX) (Scheme 29). Title compounds were tested against a series of b-galactosidases.…”

Section: Miscellaneousmentioning

confidence: 99%

“…An inversion of the stereochemistry of C-4 of the terminal sugar unit (229) was found to decrease about 40 times the inhibition; furthermore, even lower affinity was observed by changing the linkage from b-S-1,3 to b-S-1,4 (230) (Scheme 29). 124 Withers also designed 125 a series of 2-deoxy-2,2-dihalo glucosyl chlorides as a useful class of mechanism-based inhibitors of a-glucosidase; the presence of a leaving group at the anomeric position allowed trapping glycosylenzyme intermediates, what can be of interest as potential therapeutics. In this context, 2-chloro-2-deoxy-2-fluoro-a-D-glucosyl chloride derivative (232) was synthesized by a chlorination reaction of 2-fluoroglucal 231 (Scheme 30).…”

Section: -230mentioning

confidence: 99%

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Glycosidase inhibitors: versatile tools in glycobiology

López

Merino-Montiel

Martos

et al. 2012

Carbohydrate Chemistry

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Section: Miscellaneousmentioning

confidence: 99%

Section: -230mentioning

confidence: 99%

Glycosidase inhibitors: versatile tools in glycobiology

López

Merino-Montiel

Martos

et al. 2012

Carbohydrate Chemistry

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“…) a-xylosidase inhibitors [58] Sulfolobus solfatari- b-(1,4) b-galactosidase inhibitors [59] Thioglycosynthase Agrobacterium sp.…”

Section: Exo-glycosynthasesmentioning

confidence: 99%

Glycosynthases in Biocatalysis

et al. 2011

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Glycosynthases, engineered glycoside hydrolases that are able to synthesize glycans in quantitative yields without hydrolyzing them, are among the most interesting tools for the chemoenzymatic synthesis of carbohydrates that have been made available so far. From their invention in 1998, these enzymes have been developed enormously and demonstrated to be convenient alternatives to the more expensive glycosyltransferase. Glycosynthases have been proved to be efficient catalysts for the synthesis of oligosaccharides, polysaccharides, and glycoconjugates of various lengths containing different monosaccharides bound through a-and b-linkages, which have interesting applications. In this review we describe the impact that glycosynthases have had on the biocatalysis and biosynthesis of carbohydrates through the description of the novel activities produced and of the development of the glycosynthasebased process. In addition, we summarize the approaches that, according to the current literature, can be adopted to produce novel glycosynthase activities and to improve the existing process.

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“…This method has been applied to generate a number of thioglycoligases that have been useful in synthesizing glycosides containing thioglycoside linkages resistant to enzymatic cleavage. [27][28][29][30][31] The strategies of engineering glycosynthases and thioglycoligases can be combined as demonstrated by the generation of thioglycosynthases. [32] These engineered enzymes are double mutants of retaining glycosidases in which the nucleophile and acid/base residues have both been rendered noncatalytic (Fig.…”

Section: Mechanism-based Engineering Of Glycosidasesmentioning

confidence: 99%

Toward Efficient Enzymatic Glycan Synthesis: Directed Evolution and Enzyme Engineering

Kwan

Withers

2011

Journal of Carbohydrate Chemistry

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Enzymatic synthesis of oligosaccharides has traditionally employed glycosyltransferases, or glycosidases run in transglycosylation mode. Glycosynthases, mutant glycosidases in which the catalytic nucleophile has been removed, function as efficient transferases with glycosyl fluoride donors, frequently giving stoicheometric yields. Glycoligases, in which the acid/base catalyst has been mutated, synthesise sulfur-linked oligosaccharides when an activated donor is used in conjunction with a thiosugar acceptor, or in some cases O-glycosides. Recent results in the engineering and evolution of these two classes of mutant enzymes along with "classical" glycosyltransferases using a variety of screening methodologies, including robot-assisted ELISA assays and FACS cell sorting, are discussed.

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Thioglycoligase‐Based Assembly of Thiodisaccharides: Screening as β‐Galactosidase Inhibitors

Cited by 36 publications

References 47 publications

Glycosidase inhibitors: versatile tools in glycobiology

Glycosidase inhibitors: versatile tools in glycobiology

Glycosynthases in Biocatalysis

Toward Efficient Enzymatic Glycan Synthesis: Directed Evolution and Enzyme Engineering

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