A Photocleavable Auxiliary for Extended Native Chemical Ligation

To extend the scope of native chemical ligations beyond X-Cys connections, auxiliaries that contain thiol moieties were developed to mimic the function of the Cys residue in the ligation reaction/capture step. Auxiliaries known so far feature complicated attachment protocols and generally need harsh conditions for their cleavage. Herein, we present the development of a new photoremovable ligation auxiliary, which is easily synthesized and attached to peptides that contain a variety of N-terminal amino acids by a reductive amination reaction. Ligations at Gly-Gly and Ala-Gly junctions were carried out with high conversion, and the auxiliary can be cleaved from the final product by using a mild photolysis protocol. This methodological advancement is an important step forward in peptide ligation chemistry.