Tetrazole Photoclick Chemistry: Reinvestigating Its Suitability as a Bioorthogonal Reaction and Potential Applications

Abstract

The bioorthogonality of tetrazole photoclick chemistry has been reassessed. Upon photolysis of a tetrazole, the highly reactive nitrile imine formed undergoes rapid nucleophilic reaction with a variety of nucleophiles present in a biological system, along with the expected cycloaddition with alkenes. The alternative use of the tetrazole photoclick reaction was thus explored: tetrazoles were incorporated into Bodipy and Acedan dyes, providing novel photo-crosslinkers with one- and two-photon fluorescence Turn-ON properties that may be developed into protein-detecting biosensors. Further introduction of these photo-activatable, fluorogenic moieties into staurosporine resulted in the corresponding probes capable of photoinduced, no-wash imaging of endogenous kinase activities in live mammalian cells.