Synthesis and Analysis of Specific Covalent Inhibitors of endo-Xyloglucanases

A series of N‐bromoacetylglycosylamines and bromoketone C‐glycosides were synthesised from complex xyloglucan oligosaccharide (XyGO) scaffolds as specific active‐site affinity labels for endo‐xyloglucanases. Compounds based on XXXG (Xyl3Glc4) and XLLG (Xyl3Glc4Gal2) oligosaccharides exhibited striki...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2015-03, Vol.16 (4), p.575-583
Main Authors: Fenger, Thomas Hauch, Brumer, Harry
Format: Article
Language:English
Subjects:
Bacteroides - enzymology
Carbohydrate Sequence
carbohydrates
Clostridium thermocellum - enzymology
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
enzymes
Glucans - metabolism
Glycoside Hydrolases - antagonists & inhibitors
Glycoside Hydrolases - metabolism
glycosyl hydrolases
inhibitors
Molecular Sequence Data
Oligosaccharides - chemistry
Oligosaccharides - pharmacology
Substrate Specificity
Xylans - metabolism
xyloglucanases
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Summary:A series of N‐bromoacetylglycosylamines and bromoketone C‐glycosides were synthesised from complex xyloglucan oligosaccharide (XyGO) scaffolds as specific active‐site affinity labels for endo‐xyloglucanases. Compounds based on XXXG (Xyl3Glc4) and XLLG (Xyl3Glc4Gal2) oligosaccharides exhibited strikingly higher affinities and higher rates of irreversible inhibition than known cellobiosyl and new lactosyl disaccharide congeners when tested with endo‐xyloglucanases from two distinct glycoside hydrolase (GH) families. Intact‐protein mass spectrometry indicated that inactivation with XyGO derivatives generally resulted in a 1:1 labelling stoichiometry. Together, these results indicate that XyGO‐based affinity reagents have significant potential as inhibitors and proteomic reagents for the identification and analysis of diverse xyloglucan‐active enzymes in nature, to facilitate industrial enzyme applications. Affinity labels: A series of N‐bromoacetylglycosylamines and bromoketone C‐glycosides of complex xyloglucan oligosaccharides were synthesised and applied as efficient affinity labels for endo‐xyloglucanases. Thanks to their facile production and efficiency of inhibition, the new compounds are well‐suited for detailed enzymological, proteomic, and structural biological analyses of new and known endo‐(xylo)glucanases.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.201402663