Currently, there are three strategies for a glycopeptide synthesis with an oligosaccharide side chain. The first most common strategy utilizes solid-phase peptide synthesis (SPPS) with pre-formed glycosyl amino acids. Because O-glycosidic and intersaccharidic linkages are relatively labile towards acid, so it is required to select proper protecting groups to block the functional groups on both the glycan and the peptide part. Besides, proper protecting groups are of importance for the solid-phase and solution-phase synthesis of glycopeptides. Furthermore, in order to synthesize glycopeptides with complex oligosaccharide side chains, the second strategy of glycopeptide chemical or chemoenzymatic synthesis has been developed. This method utilizes a glycosyl amino acid with a relatively simple saccharide side chain in the peptide assembly and then elaborate the glycopeptide chemically or chemoenzymatically to expand the glycan. The third strategy of glycopeptides synthesis is the direct peptide glycosylation. This method does not require the use of any glycosyl amino acids and attempts to reach the maximum convergence by establishing a complex glycodomain first and then incorporating it directly into a peptide setting.
https://www.creative-biolabs.com/glycoprotein/custom-glycopeptide-synthesis.htm