An iodonium based cross-linking tool for tyrosine conjugation

Abstract

A methodology for peptide cross-linking was developed via direct fluoroalkenylation of tyrosine, utilizing a special fluoroalkyl-aryl iodonium salt derived from HFO1234yf gas. The approach enables selective conjugation of two phenolic OH groups, facilitating covalent linkage within tyrosine-containing peptides. Beyond the amino acid compatibility screening, as a key demonstration, a tyrosine-based pentapeptide was successfully cross-linked under optimized conditions, highlighting the potential of this method for peptide engineering and bioconjugation. Besides peptides, the strategy was also applicable to various functionalized phenols, to synthesize unique 1,2-diaryloxyethenes. Mechanistic insights were supported by theoretical calculations, providing a deeper understanding of the transformation pathway.