1sb1
From Proteopedia
|
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
Page seeded by OCA on Thu Feb 21 14:59:40 2008
