Target Identification of Bioactive Compounds by Photoaffinity Labeling Using Diazido Probes

Abstract

This chapter reviews a photoaffinity labeling (PAL) method which employs “diazido” probes bearing aromatic and aliphatic azido groups. Since our first report in 2004, the target molecules of various bioactive compounds have been identified by this method. It is a two-step target identification method involving the conjugation of the bioactive diazido probe with the target molecules through the selective photoreaction of the aromatic azido group and subsequent introduction of a detectable tag through a click reaction to the target molecules at the remaining aliphatic azido group. An overview of the history and recent progresses of this method, including facile methods for preparing diverse diazido building blocks, is presented, focusing mainly on the chemical aspects. The relevant methods using a bifunctional probe bearing photoreactive and bioorthogonal groups are also briefly summarized.