Oligosaccharide-derivatized dendrimers: defined multivalent inhibitors of the adherence of the cholera toxin B subunit and the heat labile enterotoxin of E. coli to GM1.
Poly(propylene imine) dendrimers having four or eight primary amino groups and a Starburst (PAMAM) dendrimer having eight primary amino groups were used as core molecules, to which phenylisothiocyanate derivatized (PITC) galbeta1-3galNAcbeta1-4[sialic acid alpha2-3]-galbeta1-4glc (oligo-GM1) residues were covalently attached to yield multivalent oligosaccharides. The synthesis of the oligo-GM1-PITC derivatized dendrimers was monitored using high performance thin layer chromatography, infrared spectroscopy, sialic acid content, and mass spectroscopy. The ability of multivalent oligo-GM1-PITC dendrimers to inhibit the binding of 125I-labeled cholera toxin B subunit and the heat labile enterotoxin of E. coli to GM1-coated microtiter wells was determined. IC50s obtained for the oligo-GM1-PITC dendrimers, GM1, and the oligosaccharide moiety of GM1 indicated that the derivatized dendrimers inhibited binding of the choleragenoid and the heat labile enterotoxin to GM1-coated wells at a molar concentration five- to 15-fold lower than native GM1 and more than 1,000-fold lower than that of the free oligosaccharide.
Thompson
J P
JP
Department of Biochemistry and Molecular Biology, The M.S. Hershey Medical Center, The Pennsylvania State University, Hershey 17033, USA.
Schengrund
C L
CL
D000818:Animals; D001388:Aziridines / Q000737:chemistry / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002417:Cattle; D002772:Cholera Toxin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004768:Enterotoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005677:G(M1) Ganglioside / Q000378:metabolism*; D008968:Molecular Conformation; D011108:Polymers; D011485:Protein Binding
D001388:Aziridines; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011108:Polymers; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli; C031132:propyleneimine