Site-Selective Functionalization of Methionine Residues via Photoredox Catalysis

被引：108

作者：

Kim, Junyong ^{[1
]}

Li, Beryl X. ^{[1
]}

Huang, Richard Y-C ^{[2
]}

Qiao, Jennifer X. ^{[3
]}

Ewing, William R. ^{[3
]}

MacMillan, David W. C. ^{[1
]}

机构：

[1] Princeton Univ, Merck Ctr Catalysis, Princeton, NJ 08544 USA

[2] Bristol Myers Squibb Co, Res & Dev, Pharmaceut Candidate Optimizat, Princeton, NJ 08542 USA

[3] Bristol Myers Squibb Co, Discovery Chem Res & Dev, Princeton, NJ 08542 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2020年 / 142卷 / 51期

关键词：

NATIVE PROTEINS; BIOCONJUGATION; PEPTIDES; REAGENTS; TYROSINE; TRYPTOPHAN; OXIDATION; FLAVINS; REDUCTION;

D O I：

10.1021/jacs.0c09926

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Bioconjugation technologies have revolutionized t he 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.

引用

页码：21260 / 21266

页数：7

共 47 条

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