Sugar mimics: An artificial receptor for cholera toxin

The paper describes the pseudosugar 2 [Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)DCCHD], a high affinity binder of cholera toxin (CT). The molecule was designed using molecular modeling techniques to mimic the natural CT membrane receptor, ganglioside GM1. The central residue of GM1, a 3,4-disubstituted galactose unit, was recognized as the ganglioside scaffold element and substituted with a conformationally locked cyclohexanediol (DCCHD). DCCHD was synthesized in enantiopure form using enantioselective Diels Alder methodology and regioselectively alpha-sialylation at the equatorial position. Glycosylation with a Gal beta(1-3)GalNAc donor completed the synthesis of 2. The solution structure of 2 and its binding ability to CT were found to be analogous to those of the GM1 oligosaccharide.