Photoclick chemistry: a fluorogenic light-triggered in vivo ligation reaction

The ability to use chemical reactivity to monitor and control biomolecular processes with a spatial and temporal precision motivated the development of light-triggered in vivo chemistries. To this end, the photoinduced tetrazole-alkene cycloaddition, also termed 'photoclick chemistry' offers a very rapid chemical ligation platform for the manipulation of biomolecules and matrices in vivo. Here we outline the recent developments in the optimization of this chemistry, ranging from the search for substrates that offer two-photon photoactivatability, superior reaction kinetics, and/or genetic encodability, to the study of the reaction mechanism. The applications of the photoclick chemistry in protein labeling in vitro and in vivo as well as in preparing 'smart' hydrogels for 3D cell culture are highlighted.