The globotriaosylceramide (Gb3) verotoxin (VT) interaction is one of several examples of glycolipid receptors where the ceramide (or lipid) free oligosaccharides fail to show the expected binding parameters. We present a novel, yet simple strategy to synthesize monovalent, water soluble glycosphingolipid mimics which retain receptor function. Replacing the fatty acid chain with rigid, three dimensional hydrocarbon frames, such as adamantane, gives a novel class of neohydrocarbon glycoconjugates. Such adamantyl conjugates derived from Gb3 showed significantly enhanced solubility in water compared to natural Gb3. Adamantyl-Gb3 showed a thousand fold enhanced inhibitory activity (IC50 = 1 microM) for VT-Gb3 binding as compared to a lipid free Gb3 oligosaccharide derivative, alphaGal1-4betaGal1-4betaGlc1-O-CH2CH(CH2SO2C 4H9)2 (IC50 > 2 mM). This represents a new approach to the generation of antagonists of glycolipid receptors.
Copyright 1999 Academic Press.