Diversity-Oriented Module Synthesis of Multibranched O-GalNAc Glycans

作者：Yuqing Xing, Yinshuang Li, Sai Yang, Shuang Li, Peixue Ling, Jingyao Qu, Junqiang Fang · 发表于：ACS Catalysis · 年份：2025 · DOI：10.1021/acscatal.5c05290 · 被引用次数：1 · 研究领域：Carbohydrate Chemistry and Synthesis、Glycosylation and Glycoproteins Research、Proteoglycans and glycosaminoglycans research

O-GalNAc glycans play pivotal roles in diverse biological and pathological processes, including cell adhesion, vascular development, immune cell trafficking, tumor growth, and progression. Despite their importance, the limited availability of asymmetrically branched O-GalNAc glycans has hindered the exploration of their structure–function relationships. Herein, we report a diversity-oriented enzymatic approach for the collective preparation of branched Core 2 O-GalNAc glycans. The Core 2 trisaccharide was enzymatically synthesized with human β1,6- N -acetylglucosaminyltransferase 1 (GCNT1) expressed in Escherichia coli . Subsequently, using well-programmed glycosyltransferase modules, the Core 2 trisaccharide was systematically extended to construct a library of multibranched O-GalNAc glycans. Glycan microarray analysis revealed the binding profiles of selected glycan-binding proteins to these synthetic structures. This comprehensive collection of synthetic Core 2 O-GalNAc glycans serves not only as valuable standards for structural identification in complex biological samples but also significantly enhances the applicability in functional O-glycomics, paving the way for targeted therapeutic development.