Tuning the leaving group in 2-deoxy-2-fluoroglucoside results in improved activity-based retaining β-glucosidase probes

Chem Commun (Camb). 2012 Oct 28;48(84):10386-8. doi: 10.1039/c2cc35653h. Epub 2012 Aug 29.

Abstract

The potency of 2-deoxy-2-fluoroglycosides in activity-based profiling of human acid β-glucosidase is drastically improved by introducing an N-phenyl trifluoroacetimidate leaving group at the anomeric center. Protonation by the general acid-base catalyst in the active site turned out to be a prerequisite, making the imidate probe a genuine mechanism-based glycosidase inactivator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemistry*
  • Acetamides / metabolism
  • Fluoroacetates / chemistry*
  • Fluoroacetates / metabolism
  • Glycosides / chemistry*
  • Glycosides / metabolism
  • Humans
  • Molecular Probes / chemistry
  • Molecular Probes / metabolism*
  • Molecular Structure
  • beta-Glucosidase / analysis*
  • beta-Glucosidase / antagonists & inhibitors
  • beta-Glucosidase / metabolism*

Substances

  • Acetamides
  • Fluoroacetates
  • Glycosides
  • Molecular Probes
  • beta-Glucosidase