3] Mechanism-based irreversible enzyme inhibitors

Abstract

There are two extreme forms of mechanism for specific irreversible enzyme inhibitors. One comprises the classical affinity labeling agents, which are substrate analogs containing chemically reactive functional groups. The specific binding of these inhibitors to the active-site regions of the enzyme ensures a greater probability of chemical reaction with a residue within this region as opposed to nonspecific chemical reactions. This chapter explains the irreversible enzyme inhibitors. It defines the conditions on which the successful design of mechanism-based irreversible enzyme inhibition is dependent. It cites specific reagents like β-γ – Unsaturated Molecules, diazoesters and ketones, Allyl chloride and sulfates, vinyl chlorides and other reagents. It also explains the synthsis of Vinyl Glycine and p-Nitrophenyl Diazoacetate. The chapter concludes that mechanism-based irreversible enzyme inhibitors are more than an enzymological curiosity and can be useful as general selective irreversible enzyme inhibitors.