2oae
From Proteopedia
(New page: 200px<br /><applet load="2oae" size="450" color="white" frame="true" align="right" spinBox="true" caption="2oae, resolution 3.000Å" /> '''Crystal structure o...) |
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| - | [[Image:2oae.gif|left|200px]]<br /><applet load="2oae" size=" | + | [[Image:2oae.gif|left|200px]]<br /><applet load="2oae" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2oae, resolution 3.000Å" /> | caption="2oae, resolution 3.000Å" /> | ||
'''Crystal structure of rat dipeptidyl peptidase (DPPIV) with thiazole-based peptide mimetic #31'''<br /> | '''Crystal structure of rat dipeptidyl peptidase (DPPIV) with thiazole-based peptide mimetic #31'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2OAE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with SO4 and AIL 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:// | + | 2OAE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=AIL:'>AIL</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=2OAE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: serine-peptidase]] | [[Category: serine-peptidase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:24:42 2008'' |
Revision as of 13:24, 23 January 2008
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Crystal structure of rat dipeptidyl peptidase (DPPIV) with thiazole-based peptide mimetic #31
Overview
A novel series of pyrrolidine-constrained phenethylamines were developed, as dipeptidyl peptidase IV (DPP4) inhibitors for the treatment of type 2, diabetes. The cyclohexene ring of lead-like screening hit 5 was replaced, with a pyrrolidine to enable parallel chemistry, and protein co-crystal, structural data guided the optimization of N-substituents. Employing this, strategy, a >400x improvement in potency over the initial hit was realized, in rapid fashion. Optimized compounds are potent and selective inhibitors, with excellent pharmacokinetic profiles. Compound 30 was efficacious in, vivo, lowering blood glucose in ZDF rats that were allowed to feed freely, on a mixed meal.
About this Structure
2OAE is a Single protein structure of sequence from Rattus norvegicus with and as ligands. Active as Dipeptidyl-peptidase IV, with EC number 3.4.14.5 Full crystallographic information is available from OCA.
Reference
Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit., Backes BJ, Longenecker K, Hamilton GL, Stewart K, Lai C, Kopecka H, von Geldern TW, Madar DJ, Pei Z, Lubben TH, Zinker BA, Tian Z, Ballaron SJ, Stashko MA, Mika AK, Beno DW, Kempf-Grote AJ, Black-Schaefer C, Sham HL, Trevillyan JM, Bioorg Med Chem Lett. 2007 Jan 19;. PMID:17276063
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