Proc Natl Acad Sci U S A
November 2024
Here, we present a series of fluorinated cationic reagents that enable rapid arylation of cysteine under mild conditions compatible with proteins and peptides. The highly polarized C-F bond and attractive nucleophile-electrophile Coulombic interactions substantially accelerate cysteine arylation, leading to unusually high rate constants on the order of 100 M·s and allowing for equimolar labeling of substrates at micromolar concentrations. The synthetic modularity of this approach promotes the direct coupling of structurally diverse phenol-containing functional motifs to cysteine residues of biomacromolecules with high efficiency.
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