Carbohydrate-Based Drug Research Center, State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Org Biomol Chem. 2024 Oct 2;22(38):7767-7785. 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, - and -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.
糖链是一种重要的细胞成分，通常以游离形式或糖缀合形式存在。糖基化影响糖缀合物在健康和疾病发展中的调节功能，表明糖链在生物体中起着关键作用。由于糖链结构的复杂性和多样性，制备结构明确的糖链具有挑战性，这阻碍了分子水平上对生物功能的研究。化学-酶合成是一种有吸引力的制备复杂糖链的方法，因为它避免了化学合成中繁琐的保护基团操作，并确保了在糖链组装过程中糖苷具有高区域和立体选择性。本文首先讨论了参与人类糖链化学-酶合成的酶，如糖基转移酶（GTs）和糖苷酶（GHs），以及糖供体。随后展示并总结了许多最新的化学-酶方法，以说明合成人类糖链的发展，例如 - 和 - 连接的糖链、人乳寡糖和糖胺聚糖。因此，我们提供了对近年来用于合成复杂人类糖链的化学-酶合成设计和应用的概述，以及对当前方法的局限性和前景的深入了解。
