Self‐Assembly of Glycolipid Epimers: Their Supramolecular Morphology Control and Immunoactivation Function

Abstract Although advances have been made in carbohydrate‐based macromolecular self‐assembly, harnessing epimers of carbohydrates to perform molecular assembly and further investigating the properties of supramolecular materials remain little explored. Herein, two classes of stereoisomeric glycolipid amphiphiles based on d ‐ N ‐acetylgalactosamine (GalNAc) are reported, and they can aggregate into ribbon‐like structures in the aqueous solution due to amphiphilic property, which allow to obtain glycocalyx‐mimicking supramolecular materials. The subtle distinction in glycoside configuration of GalNAc‐α‐SSA and GalNAc‐β‐SSA dictates the different molecular packing in self‐assembled structures. Since driven by the distinguishing carbohydrate–carbohydrate interactions, the ribbon‐like architectures transform into spherical nanostructures via mixing GalNAc‐α‐SSA and GalNAc‐β‐SSA. The resulting spherical micelles fabricated by blending glycolipid epimers can potentiate the macrophage‐ and dendritic cell‐mediated immune responses in vitro. Such glycolipid epimers will pave the way to create glycocalyx‐mimicking immune modulators by incorporating stereochemistry into supramolecular self‐assembly.