Nitro as a novel zinc-binding group in the inhibition of carboxypeptidase A.
Article Details
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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
Drug Target Property Measurement pH Temperature (°C) (2R)-2-benzyl-3-nitropropanoic acid Carboxypeptidase A1 Ki (nM) 150 N/A N/A Details L-BENZYLSUCCINIC ACID Carboxypeptidase A1 Ki (nM) 450 N/A N/A Details