2p8s
From Proteopedia
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Human dipeptidyl peptidase IV/CD26 in complex with a cyclohexalamine inhibitor
Overview
Molecular modeling was used to design a rigid analog of sitagliptin 1. The, X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the, central beta-amino butyl amide moiety could be replaced with a, cyclohexylamine group. This was confirmed by structural analysis and the, resulting analog 2a was synthesized and found to be a potent DPP-4, inhibitor (IC(50)=21nM) with excellent in vivo activity and, pharmacokinetic profile.
About this Structure
2P8S is a Single protein structure of sequence from Homo sapiens with NAG, NA and 417 as ligands. Active as Dipeptidyl-peptidase IV, with EC number 3.4.14.5 Full crystallographic information is available from OCA.
Reference
Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin., Biftu T, Scapin G, Singh S, Feng D, Becker JW, Eiermann G, He H, Lyons K, Patel S, Petrov A, Sinha-Roy R, Zhang B, Wu J, Zhang X, Doss GA, Thornberry NA, Weber AE, Bioorg Med Chem Lett. 2007 Apr 2;. PMID:17433672
Page seeded by OCA on Mon Nov 12 23:21:37 2007
Categories: Dipeptidyl-peptidase IV | Homo sapiens | Single protein | Biftu, T. | Scapin, G. | 417 | NA | NAG | Alpha/beta | Beta-propeller | Dimer | Structure-based design
