Polymorphism of Kdo-Based Glycolipids: The Elaborately Determined Stable and Dynamic Bicelles

Understanding how the diversity of glycolipids, including how their chemical structures and composition affect their biological functions, is a remarkable fundamental challenge. In this work, we employed a rare monosaccharide, 3-deoxy-D-manno-2-octulosonic acid (Kdo) to build a simple and biomimetic model to understand the diversity of glycolipids from the viewpoint of supramolecular chemistry. Kdo was chosen not only because its unusual 8-carbon acidic carbohydrate backbone is very different from common hexoses, but also because of its key structural role in lipopolysaccharides and prevalence in bacteria, plant life, and algae. It was found that although both of the two Kdo-lipids S-Kdo and Kdo-S derived from the same carbohydrate backbone and gave bicelles as their self-assembled morphology, experimental results revealed that the self-assembly showed pathway complexity. Bicelle is the thermodynamic product of S-Kdo, while for Kdo-S, the bicelle is only a kinetically trapped state, which finally transforms to a ribbon. Molecular simulation clearly revealed the different packing of Kdo-lipids in the bicelles with different contribution from hydrogen bonds and electrostatic interactions.