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    The growing prevalence of synthetically modified proteins in pharmaceuticals and materials has exposed the need for efficient strategies to enable chemical modifications with high site-selectivity. While genetic engineering can incorporate non-natural amino acids into recombinant proteins, regioselective chemical modification of wild-type proteins remains a challenge. Herein, we use photoredox catalysis to develop a site-selective tyrosine bioconjugation pathway that incorporates bioorthogonal formyl groups, which subsequently allows for the synthesis of structurally defined fluorescent conjugates from native proteins. A water-soluble photocatalyst, lumiflavin, has been shown to induce oxidative coupling between a previously unreported phenoxazine dialdehyde tag and a single tyrosine site, even in the presence of multiple tyrosyl side chains, through the formation of a covalent C-N bond. A variety of native proteins, including those with multiple tyrosines, can successfully undergo both tyrosine-specific and single-site-selective labelling. This technology directly introduces aldehyde moieties onto native proteins, enabling rapid product diversification using an array of well-established bioorthogonal functionalization protocols including the alkyne-azide click reaction. © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

    Citation

    Beryl X Li, Daniel K Kim, Steven Bloom, Richard Y-C Huang, Jennifer X Qiao, William R Ewing, Daniel G Oblinsky, Gregory D Scholes, David W C MacMillan. Site-selective tyrosine bioconjugation via photoredox catalysis for native-to-bioorthogonal protein transformation. Nature chemistry. 2021 Sep;13(9):902-908

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    PMID: 34183819

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