Comparative studies on the stability of acyl enzyme intermediates: An approach to the design of temporary inhibitors for trypsin-like enzymes.

The deacylation rates of hydrolysis of inverse substrates (p-amidinophenyl esters) catalyzed by trypsin, thrombin and plasmin were studied from the standpoint of designing inhibitors which can discriminate between trypsin-like enzymes. It was shown that plasmin and thrombin behave quite differently towards these substrates; plasmin affords more stable acyl enzymes with aromatic acyl groups than with aliphatic acyl groups, while thrombin shows the opposite behavior. The half-life time of p-methoxybenzoyl plasmin is as long as 15 h while that of p-methoxybenzoyl thrombin is 35 min. This approach seems promising for the design of selective inhibitors of trypsin-like enzymes.