Lin, S. et al. Science 355, 597–602 (2017).

A plethora of methods are available for labeling cysteine residues in proteins. Methods for labeling that other sulfur-containing amino acid, methionine, have been challenging to develop owing to its weakly nucleophilic nature. Lin et al. report an approach for selective, rapid and robust labeling of methionine using oxaziridine-based reagents. Importantly, the reaction proceeds under biocompatible conditions. They illustrate several applications, including the addition of various tags to model proteins and the construction of antibody–drug conjugates. Moreover, they show that their chemoselective methionine-labeling approach can be used in combination with mass spectrometry to identify hyper-reactive methionine residues on a global proteome scale. The approach, named ReACT (redox-activated chemical tagging), should be a useful addition to the protein-labeling toolbox.