Decarboxylative diversification of amino acids and peptides through metallaphotocatalytic editing of acidic residues

Abstract

Lysine with a characteristic amino group on its side chain is one of the most abundant amino acids in protein structures, making libraries of lysine-based noncanonical amino acids (ncAAs) a valuable resource for expanding the functional and structural diversity of amino acids and peptides, unlocking new opportunities in peptide design and chemical modification. In this study, we report the development of a metallaphotocatalytic decarboxylation strategy that can smoothly transform aspartic acid, glutamic acid, homoglutamic acid, and higher homologs into various N -aryl lysines and analogs, a highly versatile yet underexploited class of functionalized ncAAs. The resulting ncAAs feature a wide array of aromatic and heteroaromatic substituents, as well as structurally tunable aliphatic side chains. Furthermore, this strategy can also be applied to the construction of arylamine-modified peptides, providing modular access to functionalized amino acid and peptide building blocks.