| Abstract | Solution and solid phase strategies for the synthesis of α-galactose based neoglycopeptide derivatives Figure 2, Figure 3, Figure 3, Scheme 3 and Scheme 4 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, Figure 3 and Scheme 4 and Figure 3 and Scheme 4 were found to be inhibitors, IC50=2.0 mM (Figure 3 and Scheme 4) and 0.2 mM (Figure 3 and Scheme 4). All of the inhibitors (Figure 3 and Scheme 4) 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. |
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