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

Article Details

Citation

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

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

Bioorg Med Chem. 2008 Apr 1;16(7):3596-601. doi: 10.1016/j.bmc.2008.02.010. Epub 2008 Feb 8.

PubMed ID
18289863 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
(2R)-2-benzyl-3-nitropropanoic acidCarboxypeptidase A1Ki (nM)150N/AN/ADetails
L-BENZYLSUCCINIC ACIDCarboxypeptidase A1Ki (nM)450N/AN/ADetails