1sb1
From Proteopedia
(New page: 200px<br /> <applet load="1sb1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sb1, resolution 1.90Å" /> '''Novel Non-Covalent ...) |
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| - | [[Image:1sb1.gif|left|200px]]<br /> | + | [[Image:1sb1.gif|left|200px]]<br /><applet load="1sb1" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1sb1, resolution 1.90Å" /> | caption="1sb1, resolution 1.90Å" /> | ||
'''Novel Non-Covalent Thrombin Inhibitors Incorporating P1 4,5,6,7-Tetrahydrobenzothiazole Arginine Side Chain Mimetics'''<br /> | '''Novel Non-Covalent Thrombin Inhibitors Incorporating P1 4,5,6,7-Tetrahydrobenzothiazole Arginine Side Chain Mimetics'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The design, synthesis and biological activity of a series of novel | + | The design, synthesis and biological activity of a series of novel non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are described. Compound 9, the most potent in the series of thrombin inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity against trypsin. The binding mode of this novel class of thrombin inhibitors in the enzyme active site, based on the X-ray crystal structure of compound 9 co-crystallized with human alpha-thrombin, is discussed. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1SB1 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 NA and 165 as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1SB1 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=NA:'>NA</scene> and <scene name='pdbligand=165:'>165</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1SB1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: thrombin; inhibition; hirugen; serine protease inhibitor]] | [[Category: thrombin; inhibition; hirugen; serine protease inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:59:40 2008'' |
Revision as of 12:59, 21 February 2008
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Novel Non-Covalent Thrombin Inhibitors Incorporating P1 4,5,6,7-Tetrahydrobenzothiazole Arginine Side Chain Mimetics
Contents |
Overview
The design, synthesis and biological activity of a series of novel non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are described. Compound 9, the most potent in the series of thrombin inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity against trypsin. The binding mode of this novel class of thrombin inhibitors in the enzyme active site, based on the X-ray crystal structure of compound 9 co-crystallized with human alpha-thrombin, is discussed.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1SB1 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Novel non-covalent thrombin inhibitors incorporating P(1) 4,5,6,7-tetrahydrobenzothiazole arginine side chain mimetics., Marinko P, Krbavcic A, Mlinsek G, Solmajer T, Bakija AT, Stegnar M, Stojan J, Kikelj D, Eur J Med Chem. 2004 Mar;39(3):257-65. PMID:15051174
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