Expeditious synthesis of multiglycopeptides with heterogeneous glycan cores derived from an α-dystroglycan mucin-like domain

Abstract

Glycosylation is a post-translational modification prevalent in the majority of proteins. Many glycoproteins contain several glycosylation sites, often bearing different glycan moieties. The inherent difficulties of glycopeptide synthesis worsen for heterogeneously glycosylated peptides, as each glycan introduces unique synthetic hurdles. Stirring-assisted solid-phase synthesis proved extremely valuable in accessing post-translationally modified peptides. We present the stirring-assisted synthesis of a heterogeneous glycopeptide library, derived from α-dystroglycan, bearing a variety of glycosylation patterns combining both mannose and GalNAc cores. The developed strategy streamlined the expeditious assembly with post-assembly manipulation, enabling the procurement of heterogeneously glycosylated peptides with high purity.