Low molecular weight, sequence based, collagenase inhibitors selectively block the interaction between collagenase and TIMP (tissue inhibitor of metalloproteinases)

Matrix. 1990 Oct;10(5):292-9. doi: 10.1016/s0934-8832(11)80184-8.

Abstract

Sequence-based inhibitors of collagenase bearing an hydroxamate group capable of chelating the active site zinc atom were synthesized and tested. The effect of one of these molecules (RP 59794; Ki about 10(-8) M) on the formation of the TIMP: collagenase complex was also tested. RP 59794 blocks complex formation and can partially dissociate established TIMP: collagenase complexes. It exhibits the same stereospecificity in this activity as in its inhibition of collagenase suggesting that TIMP and RP 59794 both interact with the active site region of collagenase.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Amino Acids, Branched-Chain / pharmacology*
  • Animals
  • Binding Sites
  • Cattle
  • Glycoproteins / metabolism*
  • Metalloendopeptidases / antagonists & inhibitors
  • Microbial Collagenase / antagonists & inhibitors*
  • Microbial Collagenase / metabolism
  • Molecular Weight
  • Protein Binding / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Tissue Inhibitor of Metalloproteinases

Substances

  • Amino Acids, Branched-Chain
  • Glycoproteins
  • Tissue Inhibitor of Metalloproteinases
  • RP 59794
  • Metalloendopeptidases
  • Microbial Collagenase