{Reference Type}: Journal Article
{Title}: Integrated chemoenzymatic synthesis of a comprehensive sulfated ganglioside glycan library to decipher functional sulfoglycomics and sialoglycomics.
{Author}: Xu Z;Liu Y;Liu J;Ma W;Zhang Z;Chapla DG;Wen L;Moremen KW;Yi W;Li T;
{Journal}: Nat Chem
{Volume}: 16
{Issue}: 6
{Year}: 2024 Jun 6
{Factor}: 24.274
{DOI}: 10.1038/s41557-024-01540-x
{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.