Site-Selective Functionalization of Methionine Residues via Photoredox Catalysis

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-sele...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2020-12, Vol.142 (51), p.21260-21266
Main Authors: Kim, Junyong, Li, Beryl X, Huang, Richard Y.-C, Qiao, Jennifer X, Ewing, William R, MacMillan, David W. C
Format: Article
Language:English
Subjects:
Binding Sites
Catalysis
Methionine - chemistry
Oxidation-Reduction
Photochemical Processes
Proteins - chemistry
Substrate Specificity
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.0c09926