Novel synthetic approaches toward glycans and glycoproteins

Novel synthetic approaches toward glycans and glycoproteins

 

Date: 19^th November, 2024 (Tuesday)

 

Venue: Lecture Theatre P3, Chong Yuet Ming Physics Building

 

Prof. Yuta MAKI

 

Department of Chemistry

Graduate School of Science

Osaka University

 

Glycosylation is a major posttranslational modification of proteins. Although the glycosylation changes the biological activity and physicochemical properties of proteins, details and molecular mechanisms are not fully understood. Thus, synthesis of homogeneous glycans and glycoproteins is essential to elucidate functions of glycans. To access large complex-type glycans, we developed a novel semisynthetic approach using an asparagine-linked biantennary nonasaccharide, which was isolated from egg yolks, as a starting material. Based on new protection and deprotection protocols, human-type triantennary and lactosamine-repeated oligosaccharides were obtained within ten chemical conversion steps.⁽¹⁾ The semisynthesized triantennary glycan was then used for synthesis of a glycoprotein, erythropoietin (EPO). Our in vivo assay revealed that the antennary structure of complex-type glycans clearly changed the hematopoietic activity of EPO.⁽²⁾ Moreover, we employed flow-based solid-phase peptide synthesis (SPPS), which enables elongation of peptides with 3-min cycle,⁽³⁾ to rapidly access artificially glycosylated insulin derivatives as well as native glyco-polypeptides. In this presentation, we would like to present our synthetic achievements for glycans and glycoproteins.