Chemical Study of High-Mannose-Type Glycan-Related Proteins to Understand Their Functions at the Molecular Level

Abstract

N-linked glycans, including high-mannose-, complex-, and hybrid-type glycans, play key roles in various biological processes. Specifically, high-mannose-type glycans, including tetradecasaccharides (G3M9) consisting of three D-glucose (Glc), nine D-mannose (Man), and two N-acetyl-D-glucosamine (GlcNAc) residues, are essential for glycoprotein synthesis. Several high-mannose-type glycans obtained from G3M9-glycan using various glycan-processing enzymes function as regulatory signals for glycoprotein folding, secretion, and degradation. These properties highlight the importance of high-mannose-type glycans in cells. Notably, chemical biologists in the fields of glycoscience and glycotechnology have synthesized all high-mannose-type glycans and their derivatives, thereby contributing to the elucidation of the precise specificities of high-mannose-type glycan-related proteins in vitro. Chemically synthesized glycan probes are important to understand glycoprotein folding, secretion, and degradation at the molecular level. Therefore, in this review, we summarize the recent progress in the chemical synthesis approaches for high-mannose-type glycans and discuss the potential of target-specific glycan probes designed and synthesized based on the findings from functional analysis of high-mannose-type glycans.