Tag-Convertible Photocrosslinker with Click-On/Off N-Acylsulfonamide Linkage for Protein Identification.

The N-acylsulfonamide group, known as a safety-catch linker, has been applied to photoaffinity labeling (PAL) using a cinnamate-type photocrosslinker to improve the efficiency of PAL-based target identification. A bioorthogonal sulfo-click reaction was used to stably link a photocrosslinker unit with N-acylsulfonamide linkage to produce a photoactivatable probe without any protection. In addition, the crosslinked protein was selectively isolated with a small cinnamate tag via linkage disruption upon N-alkylation. Furthermore, the tag moiety was photochemically converted to a stable coumarin derivative by losing a water molecule, which is a useful property in MS-based identification.