Photoaffinity labeling in target- and binding-site identification

Future Med Chem. 2015;7(2):159-83. doi: 10.4155/fmc.14.152.


Photoaffinity labeling (PAL) using a chemical probe to covalently bind its target in response to activation by light has become a frequently used tool in drug discovery for identifying new drug targets and molecular interactions, and for probing the location and structure of binding sites. Methods to identify the specific target proteins of hit molecules from phenotypic screens are highly valuable in early drug discovery. In this review, we summarize the principles of PAL including probe design and experimental techniques for in vitro and live cell investigations. We emphasize the need to optimize and validate probes and highlight examples of the successful application of PAL across multiple disease areas.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Drug Discovery
  • Humans
  • Molecular Probes / chemical synthesis
  • Molecular Probes / chemistry
  • Molecular Probes / pharmacology*
  • Photoaffinity Labels*
  • Proteins / antagonists & inhibitors
  • Proteins / metabolism


  • Molecular Probes
  • Photoaffinity Labels
  • Proteins