Preparation of Human Oligosaccharides
The synthesis of glycoprotein was still challenging which requires efficient synthesis of homogeneous N-glycan and glycopeptide. The conventional total chemical synthesis toward N-glycan usually requires high-level synthetic technique and are time-consuming due to the structural diversity and some difficult-to-synthesize glycosidic bond. In addition, the N-glycan was not compatible with solid phase peptide synthesis (SPPS) for the synthesis of glycopeptide on resin, which requires strong acidic condition for global deprotection. In the past twenty years, the synthesis of homogenous glycoprotein is greatly facilitated by semi-synthesis of various N-glycans using sialylglycopeptide obtained from egg yolk. In 1997, the Seko group reported the extraction of sialylglycopeptide and sialylglycan from egg yolk, which paved the way for efficient and large-scale synthesis of homogeneous N-glycan for glycoprotein synthesis.[17] However, at that time, the N-glycan structure for synthesis was only limited to disialyloligosaccharides and not useful for organic synthesis.
In order to expand the scope to obtain structurally diverse homogeneous N-glycans based on sialylglycan isolated from egg yolk, our laboratory reported a semi-synthetic method utilizing enzymatic digestion to obtain 24 kinds of different N-glycan structure.[18-19] (Fig.2_1: Semi-synthesis of various complex type N-glycan for the solid phase synthesis of glycopeptide) These homogeneous N-glycan can be used for SPPS of glycopeptide. By synthesizing structurally diverse homogeneous N-glycans, this research laid the foundation for the investigation of the individual structure-function relationships of N-glycans.The triantennary N-glycan might affect the biological activity or physiological properties of glycoprotein compared to common biantennary N-glycan. However, the total chemical synthesis of homogeneous complex type triantennary oligosaccharide was difficult due to multiple steps and regioselectivity. In 2016, the Maki and Kajihara group reported the efficient semi-synthesis of triantennary N-glycan based on asialyloligosaccharide isolated and prepared from egg yolk.20 (Fig.2-2: Glycopeptide synthesis having triantennary complex saccharide using a condensing reagent in the liquid phase).[21]
