OLIGOSACCHARIDE-DERIVATIZED DENDRIMERS - DEFINED MULTIVALENT INHIBITORS OF THE ADHERENCE OF THE CHOLERA-TOXIN-B SUBUNIT AND THE HEAT-LABILEENTEROTOXIN OF ESCHERICHIA-COLI GM1

Poly(propylene imine) dendrimers having four or eight primary amino gr oups and a Starburst(TM) (PAMAM) dendrimer having eight primary amino groups were used as core molecules, to which phenylisothiocyanate deri vatized (PITC) gal beta 1-3galNAc beta 1-4[sialic acid alpha 2-3]-gal beta 1-4glc (oligo-GM1) residues were covalently attached to yield mul tivalent oligosaccharides. The synthesis of the oligo-GM1-PITC derivat ized dendrimers was monitored using high performance thin layer chroma tography, infrared spectroscopy, sialic acid content, and mass spectro scopy. The ability of multivalent oligo-GM1-PITC dendrimers to inhibit the binding of I-125-labeled cholera toxin B subunit and the heat lab ile enterotoxin of E. coli to GM1-coated microtiter wells was determin ed. IC(50)s obtained for the oligo-GM1-PITC dendrimers, GM1, and the o ligosaccharide moiety of GM1 indicated that the derivatized dendrimers inhibited binding of the choleragenoid and the heat labile enterotoxi n to GM1-coated wells at a molar concentration five-to 15-fold lower t han native GM1 and more than 1,000-fold lower than that of the free ol igosaccharide.