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.
Park
J I
JI
Center for Biofunctional Molecules and Division of Life and Molecular Sciences, Pohang University of Science and Technology, San 31 Hyojadong, Pohang 790-784, South Korea.
Kim
D H
DH
D002087:Butyrates / Q000494:pharmacology*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D043422:Carboxypeptidases A; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007097:Imines / Q000494:pharmacology*; D008958:Models, Molecular
C443754:2-benzyl-3,4-iminobutanoic acid; D002087:Butyrates; D004791:Enzyme Inhibitors; D007097:Imines; D002268:Carboxypeptidases; D043422:Carboxypeptidases A