Fluorosulfate as a Latent Sulfate in Peptides and Proteins

Sulfation widely exists in the eukaryotic proteome. However, understanding of the biological functions of sulfation in peptides and proteins has been hampered by the lack of methods to control its spatial or temporal distribution in the proteome. Herein, we report that fluorosulfotyrosine can serve as a latent precursor of sulfotyrosine in peptides and proteins, which can be efficiently converted into sulfotyrosine residues by hydroxamic acid activators under physiologically relevant conditions. Photocaging the hydroxamic acid activators further allowed for light-controlled activation of functional sulfopeptides. This work provides a valuable tool for probing functional roles of sulfation in the peptides and proteins.