2-Benzyl-3,4-iminobutanoic Acid as Inhibitor of Carboxypeptidase A

2-Benzyl-3,4-iminobutanoic acid (3) was evaluated as a novel class of inhibitor for carboxypeptidase A (CPA). All four stereoisomers of 3 are found to have competitive inhibitory activity for CPA, although their inhibitory potencies differ widely with (2R,3R)-3 being most potent. The molecular modeling study for CPA(2R,3R)-3 complex suggested that the lone pair electrons on the nitrogen of the aziridine ring in the inhibitor forms a coordinative bond with the active site zinc ion and the proton on the nitrogen is engaged in hydrogen bonding with one of the carboxylate oxygens of Glu-270.