Photoredox‐Catalyzed Labeling of Hydroxyindoles with Chemoselectivity (PhotoCLIC) for Site‐Specific Protein Bioconjugation
Soumya Jyoti Singha Roy, Conor Loynd, Delilah Jewel, Sarah E. Canarelli, Elise D. Ficaretta, Quan A. Pham, Eranthie Weerapana, Abhishek Chatterjee
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.