5-Fluoro Glycosides: A New Class of Mechanism-Based Inhibitors of Both α- and β -Glucosidases

摘要

Glycosidase inhibitors have proven to be valuable probes of enzyme mechanism and show considerable promise as therapeutic drugs. Design of inhibitors for these enzymes is best based upon a knowledge of their mechanisms. Retaining glycosidases are generally believed to follow a double-displacement mechanism in which a covalent glycosyl--enzyme intermediate is formed and hydrolyzed via oxocarbenium ion like transition states, as shown for an a-glucosidase in Scheme 1. A successful strategy for inactivation of retaining β -gly-cosidases involves the use of activated 2-deoxy-2-fluoro gly-cosides that form a stabilized 2-deoxy-2-fluoroglycosyl--enzyme intermediate that turns over only slowly.