Host–Guest Chemistry-Mediated Biomimetic Chemoenzymatic Synthesis of Complex Glycosphingolipids

作者：Yuan Ma, Yating Liu, Chang Cao, Jiarong Peng, Yinyu Jiang, Tiehai Li · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.4c17725 · 被引用次数：12 · 研究领域：Glycosylation and Glycoproteins Research、Carbohydrate Chemistry and Synthesis、Lysosomal Storage Disorders Research

Glycosphingolipids (GSLs) are amphipathic complex biomolecules constituted of hydrophilic glycans covalently linked to hydrophobic lipids via glycosidic bonds. GSLs are widely distributed in cells and tissues, where they play crucial roles in various biological functions and disease processes. However, the heterogeneity and complexity of GSLs make it difficult to explore their precise biofunctions due to obstacles in obtaining well-defined structures. Herein, we report a host-guest-chemistry-mediated biomimetic chemoenzymatic approach for the efficient synthesis of diverse complex GSLs. A key feature of this approach is that the use of methyl-β-cyclodextrin enables amphipathic glycolipids forming water-soluble inclusion complexes to improve their solubility in aqueous media, thereby facilitating enzyme-catalyzed reactions. The power and applicability of our approach are demonstrated by the streamlined synthesis of biologically important globo-, ganglio-, neolacto-, and lacto-series GSLs library containing 20 neutral and acidic glycolipids with different fucosylation and sialylation patterns. The developed method will open new avenues to easily access a wide range of complex GSLs for biomedical applications.