1z71: Difference between revisions
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|PDB= 1z71 |SIZE=350|CAPTION= <scene name='initialview01'>1z71</scene>, resolution 1.80Å | |PDB= 1z71 |SIZE=350|CAPTION= <scene name='initialview01'>1z71</scene>, resolution 1.80Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=L17:L17'>L17</scene> | |LIGAND= <scene name='pdbligand=L17:L17'>L17</scene>, <scene name='pdbligand=TYS:SULFONATED+TYROSINE'>TYS</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1z71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z71 OCA], [http://www.ebi.ac.uk/pdbsum/1z71 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1z71 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxidative metabolism, it also overcomes the metabolic liability associated with the pyrazinones. An optimization study of the P(1) benzylamide delivered the potent thrombin inhibitor 21 (K(i) = 3.2 nM, 2xaPTT = 360 nM), which exhibited good plasma levels and half-life after oral dosing in the dog (C(max) = 2.6 microM, t(1/2) = 4.5 h). | In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxidative metabolism, it also overcomes the metabolic liability associated with the pyrazinones. An optimization study of the P(1) benzylamide delivered the potent thrombin inhibitor 21 (K(i) = 3.2 nM, 2xaPTT = 360 nM), which exhibited good plasma levels and half-life after oral dosing in the dog (C(max) = 2.6 microM, t(1/2) = 4.5 h). | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wong, B.]] | [[Category: Wong, B.]] | ||
[[Category: Yan, Y.]] | [[Category: Yan, Y.]] | ||
[[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 Mon Mar 31 01:30:24 2008'' | ||
