2anm
From Proteopedia
(New page: 200px<br /> <applet load="2anm" size="450" color="white" frame="true" align="right" spinBox="true" caption="2anm, resolution 2.40Å" /> '''Ternary complex of ...) |
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| - | [[Image:2anm.gif|left|200px]]<br /> | + | [[Image:2anm.gif|left|200px]]<br /><applet load="2anm" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2anm" size=" | + | |
caption="2anm, resolution 2.40Å" /> | caption="2anm, resolution 2.40Å" /> | ||
'''Ternary complex of an orally active thrombin inhibitor with human thrombin and a c-terminal hirudin derived exo-sit inhibitor'''<br /> | '''Ternary complex of an orally active thrombin inhibitor with human thrombin and a c-terminal hirudin derived exo-sit inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Synthesis and SAR of orally active thrombin inhibitors of the | + | Synthesis and SAR of orally active thrombin inhibitors of the d-Phe-Pro-Arg type with focus on the P2-moiety are described. The unexpected increase in in vitro potency, oral bioavailability, and in vivo activity of inhibitors with dehydroproline as P2-isostere is discussed. Over a period of 24h the antithrombin activity of the most active inhibitors with IC(50)s in the nanomolar range was determined in dogs demonstrating high thrombin inhibitory activity in plasma and an appropriate duration of action after oral administration. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2ANM is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CDO as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http:// | + | 2ANM is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CDO:'>CDO</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ANM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Thrombin]] | [[Category: Thrombin]] | ||
[[Category: Baucke, D.]] | [[Category: Baucke, D.]] | ||
| - | [[Category: Hoeffken, H | + | [[Category: Hoeffken, H W.]] |
[[Category: Hornberger, W.]] | [[Category: Hornberger, W.]] | ||
| - | [[Category: Lange, U | + | [[Category: Lange, U E.W.]] |
[[Category: Mack, H.]] | [[Category: Mack, H.]] | ||
[[Category: Seitz, W.]] | [[Category: Seitz, W.]] | ||
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[[Category: blood clotting]] | [[Category: blood clotting]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:29:11 2008'' |
Revision as of 14:29, 21 February 2008
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Ternary complex of an orally active thrombin inhibitor with human thrombin and a c-terminal hirudin derived exo-sit inhibitor
Contents |
Overview
Synthesis and SAR of orally active thrombin inhibitors of the d-Phe-Pro-Arg type with focus on the P2-moiety are described. The unexpected increase in in vitro potency, oral bioavailability, and in vivo activity of inhibitors with dehydroproline as P2-isostere is discussed. Over a period of 24h the antithrombin activity of the most active inhibitors with IC(50)s in the nanomolar range was determined in dogs demonstrating high thrombin inhibitory activity in plasma and an appropriate duration of action after oral administration.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
2ANM is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Orally active thrombin inhibitors. Part 2: optimization of the P2-moiety., Lange UE, Baucke D, Hornberger W, Mack H, Seitz W, Hoffken HW, Bioorg Med Chem Lett. 2006 May 15;16(10):2648-53. Epub 2006 Feb 3. PMID:16460939
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