Inactivation of trypsin-like proteases by depsipeptides of p-guanidinobenzoic acid

Abstract
A number of esters of p-guanidinobenzoic acid were synthesized which contain a glycolyl peptide as the departing group. In the case of several enzymes, i.e., trypsin and plasma kallikrein, depsipeptides were obtained which were considerably more reactive than the ethyl ester in inactivation of the protease by acyl-enzyme formation; the depsipeptide possessing-CH2CO-Phe-NH2 as a leaving group displayed the highest reactivity. They were less effective in the case of urokinase, plasmin and urinary kallikrein. Boar acrosin was very susceptible to inactivation by both ethyl and peptidyl esters. Depsipeptides possessing a longer peptide chain and a secondary C as a leaving group showed lower activities. The results demonstrate the productive use of the departing group region of protease active centers to obtain selectivity.