Oligo-dendrimer inhibition of cholera toxin binding to GM1

While GM1 is the cell surface receptor for cholera toxin, the free oligosaccharide portion of GM1 is not as effective a Hgand as clusters of the oligosaccharide are (Schengnmd & Ringlet, J. Biol. Chem. 264: 13233, 1989). Since gangliosides may exist in clusters in cell membranes (Hakomori, Biochem. Soc. Trans. 21: 583, 1993) and are known to form micelles in water, molecules with clustered GM1 oligosaccharide residues were synthesized as potential inhibitors. Dendrimers were used as the backbone for preparation of "polyvalent" oligosaccharides. First and second generation polyfpropylene iraine) dendrimers (de-Brabander-van den Berg and Meyer, Angew. Chem. Int. Ed. 32: 1308, 1993) were synthesized and the phenylisothiocyanate derivative of oligo-GMl coupled to each terminal primary amine. First generation dendrimers had 4 oligo-GMl residues, second, 8. Their effectiveness as inhibitors was determined by their ability to inhibit binding of ¹²⁵I-labeled cholera toxin B subunit to GM1 coated microtiter wells. OligoGMl dendrimers inhibited binding of cholera toxin to the wells at concentrations -7.5 fold (4-mer) and -15 fold (8-mer) leas than native GM1.