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Ang Chem Int Ed：科学家基于霍乱毒素开发出新型有效的霍乱弧菌抑制剂

2014-07-07 佚名 生物谷

霍乱毒素抑制剂
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近日，刊登在国际杂志Angewandte Chemie International Edition上的一篇研究论文中，来自英国利兹大学等处的研究人员通过研究发现，一种新型的抑制剂可以阻断霍乱弧菌产生的霍乱毒素同肠道细胞表面的碳水化合物进行结合，这种新型抑制剂蛋白支架是基于失活的霍乱毒素而开发的，其携带有五种短糖链可以用作配体。 霍乱弧菌是一种感染性的致病菌，其主要通过食用污染过的水和食物来进

近日，刊登在国际杂志Angewandte Chemie International Edition上的一篇研究论文中，来自英国利兹大学等处的研究人员通过研究发现，一种新型的抑制剂可以阻断霍乱弧菌产生的霍乱毒素同肠道细胞表面的碳水化合物进行结合，这种新型抑制剂蛋白支架是基于失活的霍乱毒素而开发的，其携带有五种短糖链可以用作配体。

霍乱弧菌是一种感染性的致病菌，其主要通过食用污染过的水和食物来进行感染和传播，霍乱毒素可以攻击肠道细胞引发患者患危及生命的痢疾；霍乱毒素是一种蛋白质，其包含有毒素A亚单位和五个非毒素B亚单位（CTB），其形状就像一个有5个花瓣的花朵一样，霍乱毒素可以结合肠道细胞表面的特殊碳水化合物，即糖脂GM1的低聚糖单位，从而引发疾病。

为了开发阻断霍乱弧菌传播的策略，这项研究中研究者开发了一种五价的抑制剂，利用5个非毒素B亚单位作为该抑制剂蛋白质的支架；文章中，研究者通过诱导CTB亚单位上的GM1结合位点的突变，使得抑制剂并不能够结合肠道细胞，另外连接每个非毒素亚单位间的特殊链会被进行化学性修饰以使其可以承受一定的偶联反应。

研究者表示，尽管糖基的合成相对复杂一些，但是蛋白质抑制剂支架可以在工业上很容易被遗传产生，而且其也可以被进行化学修饰并且使糖类与其吸附，研究者希望这种新型技术可以被用于开发其它蛋白质-碳水化合物反应的多价抑制剂。

原始出处：

Branson TR1, McAllister TE, Garcia-Hartjes J, Fascione MA, Ross JF, Warriner SL, Wennekes T, Zuilhof H, Turnbull WB.A Protein-Based Pentavalent Inhibitor of the Cholera Toxin B-Subunit.Angew Chem Int Ed Engl. 2014 Jul 2. doi: 10.1002/anie.201404397. [Epub ahead of print]

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    2015-05-01 lilianxiang

    #霍乱弧菌#

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    2015-02-05 jklm09

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    2015-04-07 ms3830150583600765

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    2014-07-09 klivis

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