1d7x: Difference between revisions
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|PDB= 1d7x |SIZE=350|CAPTION= <scene name='initialview01'>1d7x</scene>, resolution 2.Å | |PDB= 1d7x |SIZE=350|CAPTION= <scene name='initialview01'>1d7x</scene>, resolution 2.Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SPC:N-HYDROXY+1N(4-METHOXYPHENYL)SULFONYL-4-(Z,E-N-METHOXYIMINO)PYRROLIDINE-2R-CARBOXAMIDE'>SPC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1cqr|1CQR]], [[1d5j|1D5J]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1d7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d7x OCA], [http://www.ebi.ac.uk/pdbsum/1d7x PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1d7x RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated. | The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Natchus, M G.]] | [[Category: Natchus, M G.]] | ||
[[Category: Pikul, S.]] | [[Category: Pikul, S.]] | ||
[[Category: inhibited]] | [[Category: inhibited]] | ||
[[Category: mixed alpha beta structure]] | [[Category: mixed alpha beta structure]] | ||
[[Category: zinc protease]] | [[Category: zinc protease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:36:23 2008'' | ||
