中国科学院上海药物研究所李铁海团队综合化学酶合成一个全面的磺化神经节苷聚糖文库，以破译功能的硫代糖和唾液糖。相关研究成果于2024年6月6日发表在国际顶尖学术期刊《自然—化学》。

神经节苷聚糖是一种普遍存在的复杂生物分子，涉及广泛的生物功能和疾病过程。唾液酸化和硫酸化的变化使神经节苷脂聚糖的结构复杂多样，并影响蛋白质-碳水化合物的相互作用。由于定义明确的结构的可及性有限，对这些聚糖的生物学作用的结构和功能见解受到阻碍。

该文中，研究人员报道了一种综合化酶策略，用于快速和系统地合成涵盖所有可能的，硫酸化和唾液酸化模式的综合65元神经节苷脂聚糖文库。该策略依赖于通过高度立体选择性的迭代唾液酸化、灵活的正交保护基操作的模块化位点特定硫酸化，以及使用三个唾液酸转移酶模块和一个半乳糖苷酶模块的酶催化多样化，来简化三种常见唾液酸化前体的模块化组装。

这些不同的神经节苷脂聚糖，能够使用高通量聚糖微阵列技术探索其结构-功能关系，揭示了这些聚糖上不同的硫酸化和唾液酸化模式介导其独特的结合特异性。

附：英文原文

Title: Integrated chemoenzymatic synthesis of a comprehensive sulfated ganglioside glycan library to decipher functional sulfoglycomics and sialoglycomics

Author: Xu, Zhuojia, Liu, Yating, Liu, Jialin, Ma, Wenjing, Zhang, Zhumin, Chapla, Digantkumar G., Wen, Liuqing, Moremen, Kelley W., Yi, Wen, Li, Tiehai

Issue&Volume: 2024-06-06

Abstract: Ganglioside glycans are ubiquitous and complex biomolecules that are involved in a wide range of biological functions and disease processes. Variations in sialylation and sulfation render the structural complexity and diversity of ganglioside glycans, and influence protein–carbohydrate interactions. Structural and functional insights into the biological roles of these glycans are impeded due to the limited accessibility of well-defined structures. Here we report an integrated chemoenzymatic strategy for expeditious and systematic synthesis of a comprehensive 65-membered ganglioside glycan library covering all possible patterns of sulfation and sialylation. This strategy relies on the streamlined modular assembly of three common sialylated precursors by highly stereoselective iterative sialylation, modular site-specific sulfation through flexible orthogonal protecting-group manipulations and enzymatic-catalysed diversification using three sialyltransferase modules and a galactosidase module. These diverse ganglioside glycans enable exploration into their structure–function relationships using high-throughput glycan microarray technology, which reveals that different patterns of sulfation and sialylation on these glycans mediate their unique binding specificities.

DOI: 10.1038/s41557-024-01540-x

Source: https://www.nature.com/articles/s41557-024-01540-x