1nt1: Difference between revisions
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==Overview== | ==Overview== | ||
A series of potent and selective proline- and pyrazinone-based macrocyclic | A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity. | ||
==Disease== | ==Disease== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
[[Category: Barrow, J | [[Category: Barrow, J C.]] | ||
[[Category: Krueger, J | [[Category: Krueger, J A.]] | ||
[[Category: Kuo, L | [[Category: Kuo, L C.]] | ||
[[Category: Lewis, S | [[Category: Lewis, S D.]] | ||
[[Category: Lucas, B | [[Category: Lucas, B J.]] | ||
[[Category: McMasters, D | [[Category: McMasters, D R.]] | ||
[[Category: Nantermet, P | [[Category: Nantermet, P G.]] | ||
[[Category: Newton, C | [[Category: Newton, C L.]] | ||
[[Category: Pellicore, J | [[Category: Pellicore, J M.]] | ||
[[Category: Selnick, H | [[Category: Selnick, H G.]] | ||
[[Category: Vacca, J | [[Category: Vacca, J P.]] | ||
[[Category: Yan, Y.]] | [[Category: Yan, Y.]] | ||
[[Category: Young, M.]] | [[Category: Young, M.]] | ||
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[[Category: thrombin inhibitor complex]] | [[Category: thrombin inhibitor complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:09:39 2008'' | ||
Revision as of 12:09, 21 February 2008
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thrombin in complex with selective macrocyclic inhibitor
Overview
A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1NT1 is a Single protein structure of sequence from Homo sapiens with T76 as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Design and synthesis of potent and selective macrocyclic thrombin inhibitors., Nantermet PG, Barrow JC, Newton CL, Pellicore JM, Young M, Lewis SD, Lucas BJ, Krueger JA, McMasters DR, Yan Y, Kuo LC, Vacca JP, Selnick HG, Bioorg Med Chem Lett. 2003 Aug 18;13(16):2781-4. PMID:12873514
Page seeded by OCA on Thu Feb 21 14:09:39 2008
