Inhibition of adamalysin II and MMPs by phosphonate analogues of snake venom peptides

Bioorg Med Chem. 1999 Feb;7(2):389-94. doi: 10.1016/s0968-0896(98)00243-0.

Abstract

Phosphonate analogues of the peptidomimetic N-(Furan-2-yl)carbonyl-Leu-Trp-OH were prepared with the goal of evaluating the effect of phosphonate for carboxylate replacement on binding with snake venom metalloproteinases and MMPs. N-(Furan-2-yl)carbonyl-Leu-L-Trp(P)-(OH)2 showed a 75-fold increase of the inhibiting activity against adamalysin II, a snake venom metalloproteinase structurally related to MMPs and TACE. Both the phosphonate and carboxylate peptidomimetics fit into the active site adopting a retrobinding mode and provide the structural base for a new class of metalloproteinases inhibitors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Inhibitory Concentration 50
  • Metalloendopeptidases / antagonists & inhibitors*
  • Models, Chemical
  • Snake Venoms / pharmacology*
  • Spectrophotometry, Infrared
  • Temperature

Substances

  • Snake Venoms
  • Metalloendopeptidases
  • Crotalus adamanteus proteinase II