α-Galactose based neoglycopeptides. Inhibition of verotoxin binding to globotriosylceramide Original Research Article

Solution and solid phase strategies for the synthesis of α-galactose based neoglycopeptide derivatives were developed. Neoglycopeptides generated were tested for the inhibition of verotoxin binding to globotriosylceramide (Gb3) using ELISA. Among all of the compounds tested, only the lipid derivatives of neoglycopeptides, and were found to be inhibitors, IC50=2.0 mM () and 0.2 mM (). All of the inhibitors () have a similar branching of the two α-galactosyl units at the N-terminal glycine residue of a short peptide and a lipid moiety attached at the C-terminal site. Both of these factors seem to be crucial for the inhibition. It is interesting to note that the inhibitors have only a portion of the natural trisaccharide ligand. The secondary groups either may contribute in sub-site oriented interactions with the protein receptors or may mimic the internal sugar units of the cell-surface ligand, Gb3.