Residue-Selective Protein C-Formylation via Sequential Difluoroalkylation-Hydrolysis
Mateusz Imiołek, Patrick G. Isenegger, Wai‐Lung Ng, Aziz Khan, Véronique Gouverneur, Benjamin G. Davis
Abstract
-formyl-Trp = CfW) residues. This new, unnatural protein residue CfW not only was found to be effective in bioconjugation, ligation, and labeling reactions but also displayed strong "red-shifting" of its absorption and fluorescent emission maxima, allowing direct use of Trp sites as UV-visualized fluorophores in proteins and even cells. In this way, this method for the effective generation of masked formyl-radical "HC(O)·" equivalents enables first examples of C-C bond-forming carbonylation in proteins, thereby expanding the chemical reactivity and spectroscopic function that may be selectively and post-translationally "edited" into biology.