2p8s

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(New page: 200px<br /> <applet load="2p8s" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p8s, resolution 2.20&Aring;" /> '''Human dipeptidyl pe...)
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Revision as of 21:15, 12 November 2007

Image:2p8s.gif

2p8s, resolution 2.20Å

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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

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