A Synthetic Challenge to the Diversity of Gangliosides for Unveiling Their Biological Significance

Abstract

To determine the molecular basis underlying the multiple biological functions of glycoconjugates, such as glycoproteins and glycolipids, the chemical synthesis of homogenous glycoconjugates is essential. Our research into developing synthetic methods for glycoconjugates has resulted in a convenient synthetic approach to diverse gangliosides, a family of sialic acid-containing glycosphingolipids. The major difficulties in ganglioside synthesis, which involve the construction of sialic acid-containing oligosaccharides and the conjugation of the oligosaccharide and lipid, were overcome by developing highly reactive synthetic units for glycosidating sialic acids and incorporating the lipid. Furthermore, a method for fine-tuning the hydroxyl group reactivity of sialic acids enabled the sialic acids to be dimerized and embedded in oligosaccharide sequences. These methods have been combined to synthesize diverse gangliosides and their analogs for functional studies.