2p8s: Difference between revisions
New page: left|200px<br /> <applet load="2p8s" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p8s, resolution 2.20Å" /> '''Human dipeptidyl pe... |
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[[Image:2p8s.gif|left|200px]]<br /> | [[Image:2p8s.gif|left|200px]]<br /><applet load="2p8s" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2p8s" size=" | |||
caption="2p8s, resolution 2.20Å" /> | caption="2p8s, resolution 2.20Å" /> | ||
'''Human dipeptidyl peptidase IV/CD26 in complex with a cyclohexalamine inhibitor'''<br /> | '''Human dipeptidyl peptidase IV/CD26 in complex with a cyclohexalamine inhibitor'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2P8S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, NA and 417 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] Full crystallographic information is available from [http:// | 2P8S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=417:'>417</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P8S OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: structure-based design]] | [[Category: structure-based design]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:04:42 2008'' | ||
Revision as of 10:04, 23 January 2008
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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
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