Li, J. et al. Nat. Chem. Biol. 10, 1003–1005 (2014).

The ability to 'cage' the activity of a protein in a living cell and then rapidly turn it 'on' by decaging is useful for studying its function. Several photoactivatable caging groups are available, but the wavelength of light needed for decaging can cause unwanted cellular effects, and photodecaging is not suitable for animal or deep tissue experiments. Chemical decaging offers an alternative strategy that may provide advantages in many situations. Li et al. report a bioorthogonal, biocompatible approach that utilizes the inverse electron-demand Diels-Alder reaction for chemically decaging a protected lysine, enabling them to turn on enzyme activity in live cells. As demonstrated for firefly luciferase, the decaging reaction is much faster than previously reported chemical decaging methods, comparable in speed to photodecaging methods, and may be extended to amino acids beyond lysine and to in vivo settings.