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. 2020 Dec 23;142(51):21260-21266.
doi: 10.1021/jacs.0c09926. Epub 2020 Dec 8.

Site-Selective Functionalization of Methionine Residues via Photoredox Catalysis

Junyong Kim  1 , Beryl X Li  1 , Richard Y-C Huang  2 , Jennifer X Qiao  3 , William R Ewing  3 , David W C MacMillan  1
Affiliations

Site-Selective Functionalization of Methionine Residues via Photoredox Catalysis

Junyong Kim et al. J Am Chem Soc. .

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Development of a methionine-selective bioconjugation method via photoredox catalysis.
Figure 2.
Figure 2.
Optimized conditions and proposed mechanism for the alkylation of methionine with lumiflavin photocatalyst.
Figure 3.
Figure 3.
Scope of proteins and site selectivity of the methionine bioconjugation methodology. The reaction conditions are the same as those shown in Table 1. See the Supporting Information for experimental details.
Figure 4.
Figure 4.
Functionalization of EGFP via the photoredox methionine bioconjugation protocol, (a) EGFP was initially labeled with 17, and then azides containing biological motifs were appended to the modified EGFP via CuAAC. (b) Azides bearing a biotin tag and a nonaarginine peptide, (c) After functionalization of EGFP via the photoredox methionine bioconjugation protocol, the product retained 95% of the fluorescence relative to wild-type EGFP (n = 3, mean ± SD). (d) Western blot images of wild type EGFP and modified EGFPs. (e) Confocal microscopy images of SJSA-1 cells treated with EGFP, EGFP–alkyne, and EGFP–(Arg)9. Scale bars = 20 μm.
See this image and copyright information in PMC

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