Synthesis and analysis of specific covalent inhibitors of endo-xyloglucanases

Chembiochem. 2015 Mar 2;16(4):575-83. doi: 10.1002/cbic.201402663. Epub 2015 Feb 6.

Abstract

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 (Xyl3 Glc4 ) and XLLG (Xyl3 Glc4 Gal2 ) 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.

Keywords: carbohydrates; enzymes; glycosyl hydrolases; inhibitors; xyloglucanases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteroides / enzymology*
  • Carbohydrate Sequence
  • Clostridium thermocellum / enzymology*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Glucans / metabolism
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Glycoside Hydrolases / metabolism
  • Molecular Sequence Data
  • Oligosaccharides / chemistry*
  • Oligosaccharides / pharmacology*
  • Substrate Specificity
  • Xylans / metabolism

Substances

  • Enzyme Inhibitors
  • Glucans
  • Oligosaccharides
  • Xylans
  • xyloglucan
  • Glycoside Hydrolases
  • xyloglucan endo(1-4)-beta-D-glucanase