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

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.