title: The synthesis of a multivalent heterobifunctional ligand for specific interaction with Shiga toxin 2 produced by E. coli O157:H7.
abstract: 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-α-d-galactopyranosyl residue in place of the terminal α-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-α-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).
authors.affiliation: Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Pavel I
authors.initials: PI
authors.lastname: Kitov
authors.forename: David R
authors.initials: DR
authors.lastname: Bundle
mesh_terms: D060326:Chemistry Techniques, Synthetic; D019453:Escherichia coli O157 / Q000378:metabolism*; D005690:Galactose / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D022641:Shiga Toxin 2 / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D008024:Ligands; D009844:Oligosaccharides; D022641:Shiga Toxin 2; D005690:Galactose
keywords: Escherichia coli O157:H7; Heterobifunctional ligand; P(k) trisaccharide; Shiga toxin 2; Toxin inhibitors; Trisaccharide synthesis