化学合成具有正交保护基团的GlcNAc-肽前体

Glycopeptides are a class of macromolecular compounds that combine oligosaccharides with peptides. The oligosaccharide chains in N-glycopeptides are connected to the asparagine residues of peptides through β-configured N-glycosidic bonds. Natural N-glycopeptides often have important biological activities. At present, researchers generally synthesize N-glycopeptides with multiple glycosylation sites by segmenting each N-glycopeptide with one glycosylation site and then assembling them, which reduces the synthesis efficiency. Therefore, developing a method for preparing orthogonal protected glycopeptide precursors is of great significance for the synthesis of complex N-glycopeptides. In this study, N-acetyl-D-glucosamine was used as the starting material, and two orthogonal functional groups (Ac and TIPS) were selected as sugar hydroxyl protecting groups to chemically synthesize GlcNAc-Asn modules with the above-mentioned protecting groups. Subsequently, P330-L335 containing two N-glycosylation sites in SARS-CoV-2 spike protein was used as the peptide template to synthesize GlcNAc-peptide precursors with corresponding amino acid sequences, laying the foundation for subsequent research work.