Bioorthogonal Photocatalytic Protein Labeling and Cross-Linking Enabled by Stabilized Ketyl Radicals.

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

SUBMITTER: Tan J 

PROVIDER: S-EPMC12874534 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature