Document Report Card

ID: ALA1132299

Journal: J Med Chem

Title: Phosphinic pseudo-tripeptides as potent inhibitors of matrix metalloproteinases: a structure-activity study.

Authors: Vassiliou S, Mucha A, Cuniasse P, Georgiadis D, Lucet-Levannier K, Beau F, Kannan R, Murphy G, Knäuper V, Rio MC, Basset P, Yiotakis A, Dive V.

Abstract: 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.

CiteXplore: 10411481

DOI: 10.1021/jm9900164