Light‐Cleavable Auxiliary for Diselenide–Selenoester Ligations of Peptides and Proteins

Abstract

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. Herein, the versatile multicomponent synthesis and application of a new ligation auxiliary that combines a photocleavable scaffold with the advantages of selenium‐based ligation strategies are presented. Its use was investigated 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.

Synthesis of N‐Glycosylated Soluble Fas Ligand

“…After HPLC purification, peptide 12 b was obtained in 12 % yield based on the crude material used for deprotection reactions (Figure 2). The low signal‐to‐noise ratio in the mass spectrum of 12 b is a result of low peptide solubility and poor ionization of selenium‐containing peptides [30c] …”