Identification of the cellular targets of bioactive small organic molecules using affinity reagents.
The elucidation of molecular targets of bioactive small organic molecules remains a significant challenge in modern biomedical research and drug discovery. This tutorial review summarizes strategies for the derivatization of bioactive small molecules and their use as affinity probes to identify cellular binding partners. Special emphasis is placed on logistical concerns as well as common problems encountered during such target identification experiments. The roadmap provided is a guide through the process of affinity probe selection, target identification, and downstream target validation.
Leslie
Benjamin J
BJ
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave., Urbana, IL 61801, USA.
Hergenrother
Paul J
PJ
D000345:Affinity Labels / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002477:Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D009930:Organic Chemicals / Q000138:chemical synthesis / Q000494:pharmacology*; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis*
D000345:Affinity Labels; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations