Stable acyl-derivatives of trypsin-like enzymes. Preparation, kinetics, application.

Among the inhibitors with a benzamidine moiety, 4-amidinophenyl esters of aromatic carboxylic acids that possess the structure of "inverse substrates" exhibit special kinetic characteristics. These compounds behave like substrates of trypsin-like enzymes, but acylation is much more rapid than deacylation. The result is accumulation of a comparatively stable acyl-enzyme, which may be easily isolated. By the use of 4-amidinophenyl esters acyl-derivatives of various trypsin-like enzymes can be prepared. In vivo, an acyl-enzyme behaves as an inert form of the enzyme and is protected from being inactivated by inhibitors. It is slowly reactivated in the circulation and has stimulated growing interest as a potential pro-drug.