A method for the rational design of substrate-induced, irreversible enzyme inhibitors is introduced. The said inhibitors possess hidden reactive functionalities which are unmasked at the active-site and thus can immediately react with a propinquous amino-acid residue. Hence, the enzyme, by its specific mode of action, catalyzes its own irreversible destruction. Inhibitors of this type possess manifold advantages over conventional affinity labelling agents, the most important being the increased specificity implicit in their design. In this proposal the method is applied to the inhibition of certain proteases and oxidases.
NIH ExPorter
NIH ExPorter