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| [[Image:2c8z.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2c8z| PDB=2c8z | SCENE= }} | | {{STRUCTURE_2c8z| PDB=2c8z | SCENE= }} |
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| '''THROMBIN INHIBITORS'''
| | ===THROMBIN INHIBITORS=== |
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| ==Overview==
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| The screening of fragments is an alternative approach to high-throughput screening for the identification of leads for therapeutic targets. Fragment hits have been discovered using X-ray crystallographic screening of protein crystals of the serine protease enzyme thrombin. The fragment library was designed to avoid any well-precedented, strongly basic functionality. Screening hits included a novel ligand (3), which binds exclusively to the S2-S4 pocket, in addition to smaller fragments which bind to the S1 pocket. The structure of these protein-ligand complexes are presented. A chemistry strategy to link two such fragments together and to synthesize larger drug-sized compounds resulted in the efficient identification of hybrid inhibitors with nanomolar potency (e.g., 7, IC50 = 3.7 nM). These potent ligands occupy the same area of the active site as previously described peptidic inhibitors, while having very different chemical architecture.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16480269}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16480269 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16480269}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Serine protease]] | | [[Category: Serine protease]] |
| [[Category: Thrombin]] | | [[Category: Thrombin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 21:28:20 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 12:50:14 2008'' |