Microbes and microbial toxins have long been known to bind to glycoconjugates on host cell surfaces. Since binding is an early event in infection, a potential therapeutic approach is the inhibition of attachment using competitive oligosaccharide ligands. One limitation in this approach is that intrinsically weak protein-carbohydrate affinities must be overcome for therapeutic efficacy of low-molecular weight inhibitors. This can be overcome by utilizing multivalent glycoconjugates that collectivelybind much more tightly than the corresponding monomeric species. This approach has been employed in two gastro-enteric applications where synthetic oligosaccharides are immobilized on sily laminated diatomite supports. Immobilized trisaccharide 1, SYNSORB Pk~(R) (Scheme 1) effectively binds shiga-like toxin produced by Escherlchia coli O157:H7 the causative agent of hemorrhagic colitis and hemolytic-uremic syndrome. Immobilized SYNSORB Cd~(R), trisaccharide 2, binds Toxin A produced by Clostridium difficle, the causative agent of pseudomembranous colitis and antibiotic-associated diarrhea. The supports effectively bind the respective bacterial toxins and neutralize them by preventing binding to intestinal cells.
展开▼
