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Abstract We have developed a novel visible‐light‐catalyzed bioconjugation reaction, PhotoCLIC, that enables chemoselective attachment of diverse aromatic amine reagents onto a site‐specifically installed 5‐hydroxytryptophan residue (5HTP) on full‐length proteins of varied complexity. The reaction uses catalytic amounts of methylene blue and blue/red light‐emitting diodes (455/650 nm) for rapid site‐specific protein bioconjugation. Characterization of the PhotoCLIC product reveals a unique structure formed likely through a singlet oxygen‐dependent modification of 5HTP. PhotoCLIC has a wide substrate scope and its compatibility with strain‐promoted azide‐alkyne click reaction, enables site‐specific dual‐labeling of a target protein.more » « less
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Loynd, Conor; Singha_Roy, Soumya Jyoti; Ovalle, Vincent J; Canarelli, Sarah E; Mondal, Atanu; Jewel, Delilah; Ficaretta, Elise D; Weerapana, Eranthie; Chatterjee, Abhishek (, Nature Chemistry)