Recent progress in chemoenzymatic synthesis of human glycans

• Published in: Organic & biomolecular chemistry 2024-10, Vol.22 (38), p.7767-7785
• Main Authors: Ma, Shengzhou, Gao, Jinhua, Tian, Yinping, Wen, Liuqing
• Format: Article
• Language: English
• Subjects: Breast milk; Chemical synthesis; Chemistry Techniques, Synthetic; Complexity; Free form; Glucosides; Glycan; Glycoconjugates; Glycosaminoglycans; Glycosidases; Glycoside Hydrolases - metabolism; Glycosylation; Glycosyltransferases - chemistry; Glycosyltransferases - metabolism; Humans; Oligosaccharides; Polysaccharides; Polysaccharides - biosynthesis; Polysaccharides - chemical synthesis; Polysaccharides - chemistry; Polysaccharides - metabolism
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/d4ob01006j

Glycan is an essential cell component that usually exists in either a free form or a glycoconjugated form. Glycosylation affects the regulatory function of glycoconjugates in health and disease development, indicating the key role of glycan in organisms. Because of the complexity and diversity of glycan structures, it is challenging to prepare structurally well-defined glycans, which hinders the investigation of biological functions at the molecular level. Chemoenzymatic synthesis is an attractive approach for preparing complex glycans, because it avoids tedious protecting group manipulations in chemical synthesis and ensures high regio- and stereo-selectivity of glucosides during glycan assembly. Herein, enzymes, such as glycosyltransferases (GTs) and glycosidases (GHs), and sugar donors involved in the chemoenzymatic synthesis of human glycans are initially discussed. Many state-of-the-art chemoenzymatic methodologies are subsequently displayed and summarized to illustrate the development of synthetic human glycans, for example, N - and O -linked glycans, human milk oligosaccharides, and glycosaminoglycans. Thus, we provide an overview of recent chemoenzymatic synthetic designs and applications for synthesizing complex human glycans, along with insights into the limitations and perspectives of the current methods. This work reviewed the recent progress in the chemoenzymatic synthesis of human glycans and provides insights into the limitations and perspectives of the current methods.