On-resin Photochemical Decarboxylative Arylation of Peptides

Here we describe the application of photochemical decarboxylative arylation as a late-stage modification reaction for peptides. The reaction uses redox active esters of aspartic acid and glutamic acid on solid phase to provide analogues of aromatic amino acids. By using aryl bromides as arylation reagents a wide variety of amino acids can be accessed without having to synthesize them individually in solution. The reaction is compatible with proteinogenic amino acids and was used to perform a structure-activity relationship study on a PRMT5 binding peptide.