Red-Light-Induced Cysteine Modifications Suitable for Protein Labeling

The naturally low abundance of cysteine in proteins, combined with its propensity to undergo thiol-ene reactions, makes it a preferred amino acid for various bioconjugations. However, most of these methods rely on the use of UV radiation, radical initiators, or heavy-metal-based photocatalysts, which limits their applicability in complex biological environments. Herein, we report a photocatalyzed thiol-ene radical reaction that overcomes these limitations by employing a porphyrin-based photocatalyst and low-energy red light. This method operates under mild reaction conditions and can be expanded to a cysteinyl desulfurization reaction. As this approach proceeds in aqueous media and facilitates selective transformations of both simple free cysteine and cysteine residues within complex protein, it significantly expands the existing toolbox for cysteine bioconjugation.