Catalytic Phosphorylation of Tyrosine via a Radical Arbuzov Reaction.

Synthetic protein/peptide modification is a powerful strategy for the development of new therapeutics and tools for chemical biology. Accordingly, the development of a synthetic variant of biological tyrosine phosphorylation, a cornerstone of the post-translational modification landscape, could find widespread application in the study of this fundamental biochemical signal. This work describes the development of a mechanistically novel, redox-neutral, photocatalytic tyrosine phosphorylation reaction via a radical Arbuzov-type mechanism.

Umpolung Phosphorylation of Tyrosine via 1,2-Phospha-Brook Rearrangement.

Phosphorylated tyrosine is a fundamental building block of bioactive peptides and proteins. However, the chemoselective phosphorylation of tyrosine over other nucleophilic amino acid residues in unprotected peptides remains a significant challenge. Here we report an umpolung strategy that converts the C-terminal tyrosine into an electrophilic spirolactone cyclohexadienone motif through hypervalent iodine oxidation, followed by a 1,2-phospha-Brook rearrangement using phosphite diesters as nucleophilic phosphoryl donors.

Lipid- and protein-directed photosensitizer proximity labeling captures the cholesterol interactome.

The physical properties of cellular membranes, including fluidity and function, are influenced by protein and lipid interactions. In situ labeling chemistries, most notably proximity-labeling interactomics are well suited to characterize these dynamic and often fleeting interactions. Established methods require distinct chemistries for proteins and lipids, which limits the scope of such studies.