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

被引:9
作者
Jacobson, Jared M. [1 ]
Kitov, Pavel I. [1 ]
Bundle, David R. [1 ]
机构
[1] Univ Alberta, Dept Chem, Alberta Glyc Ctr, Edmonton, AB T6G 2G2, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
Shiga toxin 2; P-k trisaccharide; Toxin inhibitors; Trisaccharide synthesis; Heterobifunctional ligand; Escherichia coli O157:H7; HEMOLYTIC-UREMIC SYNDROME; AMYLOID-P COMPONENT; ESCHERICHIA-COLI; TERMINAL ALKYNES; PATHOGENESIS; ASSOCIATION; ACETALS; AZIDES;
D O I
10.1016/j.carres.2013.05.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4 / 14
页数:11
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