ArticleJournal of the American Chemical Society2025
Bioorthogonal Photocatalytic Protein Labeling and Cross-Linking Enabled by Stabilized Ketyl Radicals.
Article in Journal of the American Chemical Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Radical reactions offer transformative potential in biological contexts but remain constrained by poor selectivity and off-target reactivity. We address these limitations through visible-light photocatalytic generation of diaryl ketyl radicals from benzophenones. This strategy circumvents traditional UV excitation pathways by suppressing triplet diradical formation─which drives nonspecific [2 + 2] cycloadditions and H atom abstraction─in favor of bioorthogonal radical-radical coupling. Our platform enables precise live-cell protein labeling with minimal cytotoxicity, including in sensitive primary neuronal cultures, and achieves site-specific modification via genetically incorporated benzophenone-based unnatural amino acids Bpa. The spatial selectivity of this approach exceeds conventional UV-based cross-linking methods, facilitating site-to-site analysis of tertiary protein interactions in structurally defined complexes. We demonstrate these capabilities by (1) quantifying dimerization interfaces of the Diels-Alderase PyrI4 and (2) resolving Bcl-X
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