Near-Infrared Photoredox Catalyzed Fluoroalkylation Strategy for Protein Labeling in Complex Tissue Environments

The chemical transformation of aromatic amino acids has emerged as an attractive alternative to nonselective lysine or cysteine labeling for the modification of biomolecules. However, this strategy has largely been limited by the scope of functional groups and the biocompatible reaction conditions available. Herein, we report the implementation of near-infrared-activatable photocatalysts, TTMAPP and (n)-Pr-DMQA(+), capable of generating fluoroalkyl radicals for peptide functionalization and protein labeling within simple and complex biological systems. At the peptide level, a diverse set of iodoperfluoroalkyl reagents were used in the functionalization and stapling of tryptophan residues. Using this photoredox catalyzed perfluoroalkylation technology, we achieved biotinylation of intracellular proteins in live cells. Notably, given the inherent tissue penetrant nature of near-infrared light, we further demonstrated the utility of this technology to achieve photocatalytic protein fluoroalkylation in patient-derived normal and tumor tissue for downstream confocal imaging and mass spectrometry-based proteomic analysis.