A new type of carboxypeptidase A inhibitors designed using an imidazole as a zinc coordinating ligand.
2-(4-Imidazoyl)hydrocinnamic acid (1) and its congeners (2-4) having different length of alkyl chain spacers between the imidazole ring and the alpha-carbon to the carboxylate of 1 have been designed, synthesized and evaluated as inhibitors for carboxypeptidase A to show that they are competitive inhibitors for the enzyme. Inhibitor 1 was most potent having the Ki value of 0.8 microM. The present study demonstrates that imidazole ring is an effective zinc coordinating ligand that can be useful for the design of inhibitors for zinc proteases.
Lee
K J
KJ
Center for Biofunctional Molecules, Pohang University of Science and Technology, Korea.
Joo
K C
KC
Kim
E J
EJ
Lee
M
M
Kim
D H
DH
D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D043422:Carboxypeptidases A; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015032:Zinc / Q000737:chemistry*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D008024:Ligands; C029899:imidazole; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D015032:Zinc