INHIBITION OF THE INTERACTION OF ENTEROTOXINS FROM THE CHOLERA TOXIN FAMILIY TO THE MEMBRANE RECEPTOR BY POLYVALENT GM1 OLIGOSACCHARIDE DERIVATIVES.
Diema Claudio D, Mitzutamari Roxana K, Landa Carlos A, Rodríguez Pablo EA, Monferran CG
The aim of this study was to examine the ability of polyvalent GM1 oligosaccharide (o-GM1, gal(beta)1-3galNAc(beta)1-4[sialic acid(afa)2-3]-gal(beta)1-4glc) derivatives covalently coupled to chitosan on the interaction of cholera toxin (CT) or the heat-labile toxins of E. coli infecting human (LTh) or porcine (LTp) intestines with GM1-coated plastic microtiter wells. Several concentrations of the different compounds were preincubated with 125I-labeled toxin and then added to the GM1-containing interface. The concentration of compound needed to inhibit binding of toxin to GM1 by 50% (IC50) was calculated. The IC50 obtained for the most effective inhibitor GM1-chitosan (o-GM1 containing a fatty acid residue) was similar to the IC50 obtained for GM1. The o-GM1-chitosan was about 1000 times less effective than GM1. The absence of the sialosyl moiety on the GM1 oligosaccharide (asialo o-GM1-chitosan) rendered the compound also a very poor inhibitor (IC50) 1000 times lower than the one for GM1. Similar resultswere obtained for CT, LTh and LTp when assayed in the same conditions. The low blocking effect observed with o-GM1-chitosan may be due to some requeriments of the hydrophobic moiety of GM1in the interaction with enterotoxins from the cholera toxin family.
