Site-Selective Functionalization of Methionine Residues via Photoredox Catalysis
Junyong Kim, Beryl X. Li, Richard Y.‐C. Huang, Jennifer X. Qiao, William R. Ewing, David W. C. MacMillan
Abstract
Bioconjugation technologies have revolutionized the practice of biology and medicine by allowing access to novel biomolecular scaffolds. New methods for residue-selective bioconjugation are highly sought to expand the toolbox for a variety of bioconjugation applications. Herein we report a site-selective methionine bioconjugation protocol that uses photoexcited lumiflavin to generate open-shell intermediates. This reduction-potential-gated strategy enables access to residues unavailable with traditional nucleophilicity-based conjugation methods. To demonstrate the versatility and robustness of this new protocol, we have modified various proteins and further utilized this functional handle to append diverse biological payloads.