Phosphinic Pseudo-Tripeptides as Potent Inhibitors of Matrix Metalloproteinases: A Structure−Activity Study
| Autor: | Marie-Christine Rio, Philippe Cuniasse, Vera Knäuper, and Athanasios Yiotakis, Dimitris Georgiadis, Gillian Murphy, Paul Basset, Vincent Dive, ‡ Karine Lucet-Levannier, Artur Mucha, Fabrice Beau, Stamatia Vassiliou, Rama Kannan |
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| Rok vydání: | 1999 |
| Předmět: |
Gelatinases
Oligopeptide Magnetic Resonance Spectroscopy biology Phosphines Stereochemistry Chemistry Metalloendopeptidases Tripeptide Matrix metalloproteinase Kinetics Structure-Activity Relationship chemistry.chemical_compound Enzyme inhibitor Drug Discovery Peptide synthesis biology.protein Molecular Medicine Structure–activity relationship Protease Inhibitors Matrilysin Oligopeptides |
| Zdroj: | Journal of Medicinal Chemistry. 42:2610-2620 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm9900164 |
| Popis: | Several phosphinic pseudo-tripeptides of general formula R-XaaPsi(PO(2)-CH(2))Xaa'-Yaa'-NH(2) were synthesized and evaluated for their in vitro activities to inhibit stromelysin-3, gelatinases A and B, membrane type-1 matrix metalloproteinase, collagenases 1 and 2, and matrilysin. With the exception of collagenase-1 and matrilysin, phosphinic pseudo-tripeptides behave as highly potent inhibitors of matrix metalloproteinases, provided they contain in P(1)' position an unusual long aryl-alkyl substituent. Study of structure-activity relationships regarding the influence of the R and Xaa' substituents in this series may contribute to the design of inhibitors able to block only a few members of the matrix metalloproteinase family. |
| Databáze: | OpenAIRE |
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