A Light Cleavable Auxiliary for Diselenide-Selenoester Ligations of Peptides and Proteins

Diselenide-selenoester ligations are increasingly used for the synthesis of proteins. Excellent ligation rates, even at low concentrations, in combination with mild and selective deselenization conditions can overcome some of the most severe challenges in chemical protein synthesis. Here we present the versatile multicomponent synthesis and application of a new ligation auxiliary that combines a photocleavable scaffold with the advantages of selenium-based ligation strategies. We investigate its use with respect to different ligation junctions and describe a novel para-methoxybenzyl deprotection reaction for the selenol moiety. The glycine-based auxiliary enabled successful synthesis of the challenging target protein G-CSF.