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

J Med Chem. 1999 Jul 15;42(14):2610-20. doi: 10.1021/jm9900164.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Metalloendopeptidases / antagonists & inhibitors*
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Phosphines / chemical synthesis*
  • Phosphines / chemistry
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Structure-Activity Relationship

Substances

  • Oligopeptides
  • Phosphines
  • Protease Inhibitors
  • Metalloendopeptidases