Binding of Vibrio cholera Toxin and the Heat-labile Enterotoxin of Escherichia coli to GM1, Derivatives of GM1, and Nonlipid Oligosaccharide Polyvalent Ligands

Structural foundation for the design of receptor antagonists targeting Escherichia coli heat-labile enterotoxin

“…The residues comprising the galactose-binding site on the toxin are strictly conserved among all sequences reported for isolates of both LT and CT, with a single exception (His/Arg13) discussed later. The significant role played by the galactose moiety of G M1 is also evident from the reduction in affinity for the toxin if the terminal galactose is not present; for CT, the IC 50 measured via competitive ELISA increases from 25 nM to 410 nM in the absence of the terminal galactose [17].…”

Mimics of ganglioside GM1 as cholera toxin ligands: replacement of the GalNAc residueElectronic supplementary information (ESI) available: synthetic details, product characterisations and full NOE contact list. See http://www.rsc.org/suppdata/ob/b2/b210503a/

“…This approach has been validated 5 using as a model system the recognition pair composed of the head-group of ganglioside GM1 1 (Chart 1) and the two bacterial enterotoxins (cholera toxin (CT) and heat-labile toxin of E. coli (LT)) that use it as their target on cell membranes. GM1 interacts with CT and LT using the Gal and NeuAc residues at the oligosaccharide non-reducing end, as has been shown by biochemical 6 and structural 7 studies. Not long ago, we described the rational design and the synthesis of the pseudo-oligosaccharide 2 5,8 (Chart 1), a functional and structural mimic of ganglioside GM1 based on the use of a conformationally restricted cyclohexanediol (CHD) 3 to replace the reducing end of the ganglioside head-group, which is not involved in toxin binding.…”

Stannyl ceramides as efficient acceptors for synthesising β-galactosyl ceramides

“…3 This and other findings have stimulated the research in the synthesis of glycosphingolipids, 1a,b,4 ceramides 4a,b and sphingosines 4a, 5 as an alternative to the natural sources. 6 The current retrosynthetic analysis reveal three important steps in the syntheses of b-GalCer 4: (i) glycosylation of the sphingosine moiety, (ii) N-acylation with the fatty acid and finally (iii) elimination of the protecting groups (Fig. 2).…”