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ID: ALA1142385

Journal: Bioorg Med Chem

Title: Nitro as a novel zinc-binding group in the inhibition of carboxypeptidase A.

Authors: Wang SH, Wang SF, Xuan W, Zeng ZH, Jin JY, Ma J, Tian GR.

Abstract: 2-Substituted 3-nitropropanoic acids were designed and synthesized as inhibitors against carboxypeptidase A (CPA). (R)-2-Benzyl- 3-nitropropanoic acid showed a potent inhibition against CPA (K(i)=0.15 microM). X-ray crystallography discloses that the nitro group well mimics the transition state occurred in the hydrolysis catalyzed by CPA, that is, an O,O'-bidentate coordination to the zinc ion and the two respective hydrogen bonds with Glu-270 and Arg-127. Because the nitro group is a planar species, we proposed (R)-2-benzyl-3-nitropropanoic acid as a pseudo-transition-state analog inhibitor against CPA.

CiteXplore: 18289863

DOI: 10.1016/j.bmc.2008.02.010