1d7x
From Proteopedia
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'''CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A MODIFIED PROLINE SCAFFOLD BASED INHIBITOR.''' | '''CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A MODIFIED PROLINE SCAFFOLD BASED INHIBITOR.''' | ||
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[[Category: Natchus, M G.]] | [[Category: Natchus, M G.]] | ||
[[Category: Pikul, S.]] | [[Category: Pikul, S.]] | ||
| - | [[Category: | + | [[Category: Inhibited]] |
| - | [[Category: | + | [[Category: Mixed alpha beta structure]] |
| - | [[Category: | + | [[Category: Zinc protease]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:33:00 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:33, 2 May 2008
CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A MODIFIED PROLINE SCAFFOLD BASED INHIBITOR.
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.
About this Structure
1D7X is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Design, synthesis, and biological evaluation of matrix metalloproteinase inhibitors derived from a modified proline scaffold., Cheng M, De B, Almstead NG, Pikul S, Dowty ME, Dietsch CR, Dunaway CM, Gu F, Hsieh LC, Janusz MJ, Taiwo YO, Natchus MG, Hudlicky T, Mandel M, J Med Chem. 1999 Dec 30;42(26):5426-36. PMID:10639284 Page seeded by OCA on Fri May 2 13:33:00 2008
