alpha-galactose based neoglycopeptides. Inhibition of verotoxin binding toglobotriosylceramide

Solution and solid phase strategies for the synthesis of a-galactose based neoglycopeptide derivatives 2-13 were developed. Neoglycopeptides generated were tested for the inhibition of verotoxin binding to globotriosylceramid e (Gb3) using ELISA. Among all of the compounds tested, only the lipid deri vatives of neoglycopeptides, 11, 12 and 13 were found to be inhibitors, IC5 0 = 2.0 mM (11b and 12c) and 0.2 mM (11c and 13c). All of the inhibitors (1 1b, 11c, 12c and 13c) have a similar branching of the two alpha-galactosyl units at the N-terminal glycine residue of a short peptide and a lipid moie ty attached at the C-terminal site. Both of these factors seem to be crucia l for the inhibition. It is interesting to note that the inhibitors have on ly a portion of the natural trisaccharide ligand. The secondary groups eith er may contribute in sub-site oriented interactions with the protein recept ors or may mimic the internal sugar units of the cell-surface ligand, Gb3. (C) 1999 Elsevier Science Ltd. All rights reserved.