Covalent glycosidase inhibitors

The area of covalent glycosidase inhibitors has recently been highlighted in an excellent review that also includes compounds containing such reporter groups as photolabile functional groups as photoaffinity probes, and others.161... 

Some of the more reactive irreversible inhibitors have been variously called suicide substrates, koa inhibitors, and mechanism-based inhibitors. These compounds are relatively innocuous substrate analogs until converted by the enzyme to highly reactive products capable of covalent attachment at the active site. Since the enzyme mechanism is involved, the covalently conjugated amino acid is often directly involved in catalysis. There has recently been increased interest in mechanism-based glycosidase inhibitors because of their value in studying the reaction mechanism (4, 48) and in their potential therapeutic application 47). 

B. P. Rempel and S. G. Withers, Covalent inhibitors of glycosidases and their applications in... 

Gloster, T.M., Roberts, S., Ducros, V.M., Perugino, G., Rossi, M., Hoos, R., Moracci, M., Vasella, A. and Davies, G.J. (2004) Structural studies of the beta-glycosidase from Sulfolobus solfataricus in complex with covalently and noncovalently bound inhibitors. 

Laitinen T, Rouvinen J, Perakyla M (1998) Ab initio quantum mechanical and density functional theory calculations on nucleophile- and nucleophile and acid-catalyzed opening of an epoxide ring a model for the covalent binding of epoxyalkyl inhibitors to the active site of glycosidases. J Org Chem 63(23) 8157-8162... 

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