Using specificity to strategically target proteases

Bioorg Med Chem. 2009 Feb 1;17(3):1094-100. doi: 10.1016/j.bmc.2008.03.068. Epub 2008 Mar 30.


Proteases are a family of naturally occurring enzymes in the body whose dysregulation has been implicated in numerous diseases and cancers. Their ability to selectively and catalytically turnover substrate adds both signal amplification and functionality as parameters for the detection of disease. This review will focus on the development of activity-based methodologies to characterize proteases, and in particular, the use of positional scanning, synthetic combinatorial libraries (PS-SCL's), and substrate activity screening (SAS) assays. The use of these approaches to better understand a protease's natural substrate will be discussed as well as the technologies that emerged.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Combinatorial Chemistry Techniques
  • Molecular Probes
  • Peptide Hydrolases / chemistry*
  • Peptide Hydrolases / metabolism
  • Peptide Library
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry*
  • Small Molecule Libraries
  • Substrate Specificity


  • Molecular Probes
  • Peptide Library
  • Protease Inhibitors
  • Small Molecule Libraries
  • Peptide Hydrolases