Assessment in mice of the therapeutic potential of tailored, multivalent Shiga toxin carbohydrate ligands
Assessment in mice of the therapeutic potential of tailored, multivalent Shiga toxin carbohydrate ligands
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DOI：
10.1086/373996
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发表时间：
2003-02-15
影响因子：
6.4
通讯作者：
Armstrong, GD
中科院分区：
文献类型：
--
作者：
Mulvey, GL;Marcato, P;Armstrong, GD
在小鼠中测定了滋贺毒素（Stx）1和Stx 2的2种可溶性多价受体抑制剂的治疗潜力。其中之一，海星，保护小鼠时，它与致命剂量的Stx 1混合皮下注射，但不是Stx 2。海星还减少了I-125-Stx 1而不是I-125-Stx 2在小鼠肾脏和大脑中的分布。海星的一个修改版本，称为“雏菊”，其中Stx alphaGal（1，4）betaGal（1，4）betaGlc受体通过修改的拴系策略安装在核心葡萄糖结构上，保护小鼠免受Stx 1和Stx 2的侵害。Daisy还可以保护经链球菌处理的小鼠免受大肠杆菌O 91：H21的侵害，并且不会干扰小鼠免疫系统产生Stx特异性保护性抗体的能力。这些结果扩展了使用可溶性碳水化合物受体抑制剂预防肠出血性大肠杆菌感染引起的Stx介导的并发症的可能性。大肠杆菌血清型。
The therapeutic potential of 2 soluble multivalent receptor-based inhibitors of Shiga toxin (Stx) 1 and Stx2 was determined in mice. One of these, Starfish, protected mice when it was injected subcutaneously in admixture with a lethal dose of Stx1 but not Stx2. Starfish also reduced the distribution of I-125-Stx1 but not I-125-Stx2 to the murine kidney and brain. A modified version of Starfish, called "Daisy," in which the Stx alphaGal(1,4)betaGal(1,4)betaGlc receptors were installed on the core glucose structure via a modified tethering strategy, protected mice against both Stx1 and Stx2. Daisy also protected streptomycin-treated mice from Escherichia coli O91:H21 and did not interfere with the ability of the murine immune system to produce Stx-specific protective antibodies. These results extend the possibility of using soluble carbohydrate-based receptor inhibitors to prevent Stx-mediated complications arising from infections with enterohemorrhagic E. coli serotypes.