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rdf:type |
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|
lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1998-2-27
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pubmed:abstractText |
For most of the known synthetic inhibitors of matrix metalloproteinases (MMPs), a substrate-like binding mode was postulated on the basis of X-ray crystallographic structures of MMP/inhibitor complexes. Conversely, the malonic acid-based inhibitor (2R,S)-HONH-CO-CH(i-Bu)-CO-Ala-Gly-NH2 was found to bind in a surprisingly different manner. Using this compound as a new lead structure, the interaction sites with human neutrophil collagenase (MMP8) were optimized with a series of iteratively designed analogues and with the help of X-ray structural analysis of selected inhibitors to finally produce low molecular weight nonpeptidic compounds of 500-1000-fold improved inhibitory potency.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-2623
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pubmed:author |
|
|
pubmed:issnType |
Print
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pubmed:day |
29
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
339-45
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9464365-Collagenases,
pubmed-meshheading:9464365-Crystallography, X-Ray,
pubmed-meshheading:9464365-Drug Design,
pubmed-meshheading:9464365-Enzyme Inhibitors,
pubmed-meshheading:9464365-Humans,
pubmed-meshheading:9464365-Magnetic Resonance Spectroscopy,
pubmed-meshheading:9464365-Malonates,
pubmed-meshheading:9464365-Matrix Metalloproteinase 8,
pubmed-meshheading:9464365-Molecular Structure,
pubmed-meshheading:9464365-Spectrometry, Mass, Fast Atom Bombardment
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|
pubmed:year |
1998
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|
pubmed:articleTitle |
Design and synthesis of malonic acid-based inhibitors of human neutrophil collagenase (MMP8).
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|
pubmed:affiliation |
Max-Planck-Institut für Biochemie, Martinsried, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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