To bind zinc or not to bind zinc: an examination of innovative approaches to improved metalloproteinase inhibition

Biochim Biophys Acta. 2010 Jan;1803(1):72-94. doi: 10.1016/j.bbamcr.2009.08.006. Epub 2009 Aug 25.

Abstract

This short review highlights some recent advances in matrix metalloproteinase inhibitor (MMPi) design and development. Three distinct approaches to improved MMP inhibition are discussed: (1) the identification and investigation of novel zinc-binding groups (ZBGs), (2) the study of non-zinc-binding MMPi, and (3) mechanism-based MMPi that form covalent adducts with the protein. Each of these strategies is discussed and their respective advantages and remaining challenges are highlighted. The studies discussed here bode well for the development of ever more selective, potent, and well-tolerated MMPi for treating several important disease pathologies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Design*
  • Humans
  • Metalloproteases / antagonists & inhibitors*
  • Metalloproteases / chemistry
  • Metalloproteases / classification
  • Models, Molecular
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Substrate Specificity / drug effects
  • Zinc / metabolism*

Substances

  • Protease Inhibitors
  • Metalloproteases
  • Zinc