The synthesis of a multivalent heterobifunctional ligand for specific interaction with Shiga toxin 2 produced by E. coli O157:H7

Hemolytic uremic syndrome is a potentially fatal complication of food poisoning caused by Escherichia coli O157:H7, especially those strains that produce the Stx2 Shiga toxin. Multivalent inhibitors based on the P-k trisaccharide are most effective against Stx1 the less dangerous of the two Shiga toxins. Inhibitors containing a terminal 2-acetamido-2-deoxy-alpha-D-galactopyranosyl residue in place of the terminal alpha-D-galactopyranosyl residue of P-k trisaccharide have been shown to exhibit preferential binding to Stx2. A multivalent heterobifunctional P-k analog containing 2-acetamido-2-deoxy-alpha-D-galactopyranose has been synthesized in a format that facilitates the ablation of toxin activity via supramolecular complex formation between Stx and the endogenous protein, Human serum amyloid P component (HuSAP). (C) 2013 Elsevier Ltd. All rights reserved.