Alpha-alkylcysteines as Inhibitors for Carboxypeptidase A. Synthesis, Evaluation, and Implication for Inhibitor Design Strategy

(R,S)- and (R)-2-Benzylcysteine (1) and (R,S)-2-phenethylcysteine (2) were synthesized and evaluated as inhibitors for carboxypeptidase A (CPA) with the expectation that these compounds exhibit improved inhibitory activities over 2-benzyl-3-mercaptopropanoic acid (BMPA), a potent CPA competitive inhibitor, possibly having additional interactions of their amino group with the carboxylate of Glu-270 of the enzyme upon binding to CPA. Contrary to the expectation, however, the CPA inhibitory potencies of these compounds were found to be much reduced compared with that of BMPA, suggesting that the amino group in the inhibitors rather exerts steric hindrance in binding of these inhibitors to CPA.