1sb1 | pdb_00001sb1
Novel Non-Covalent Thrombin Inhibitors Incorporating P1 4,5,6,7-Tetrahydrobenzothiazole Arginine Side Chain Mimetics
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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 NA and 165 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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