Ribosome-inactivating proteins: from plant defense to tumor attack.

Ribosome-inactivating proteins: from plant defense to tumor attack.
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DOI:
10.3390/toxins2112699
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发表时间:
2010-11
期刊:
影响因子:
4.2
通讯作者:
Fabbrini MS
Fabbrini MS
中科院分区:
医学2区
文献类型:
--
作者:
de Virgilio M;Lombardi A;Caliandro R;Fabbrini MS

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核糖体失活蛋白(riboase -inactivating protein, RIPs)是一种EC3.2.32.22 n -糖苷酶,它识别23S/25S/28S rRNA中普遍保守的茎环结构,去纯化单个腺嘌呤(在大鼠中为A4324)并不可逆地阻断蛋白质翻译,最终导致中毒的哺乳动物细胞死亡。蓖麻毒素是一种植物RIP原型,它包含一个催化a亚基,连接一个半乳糖结合凝集素B亚基,在大多数哺乳动物细胞中允许细胞表面结合和毒素进入,显示出在皮摩尔范围内的效力。利用植物rip作为对抗癌细胞的武器,最有希望的方法要么是设计分子,其中的毒性区域与选择性肿瘤靶向区域相关联,要么是直接作为自杀基因传递给癌症基因治疗。在这里,我们将全面介绍植物rip的概况,并讨论具有治疗潜力的嵌合分子的成功设计和特征。
Ribosome-inactivating proteins (RIPs) are EC3.2.32.22 N-glycosidases that recognize a universally conserved stem-loop structure in 23S/25S/28S rRNA, depurinating a single adenine (A4324 in rat) and irreversibly blocking protein translation, leading finally to cell death of intoxicated mammalian cells. Ricin, the plant RIP prototype that comprises a catalytic A subunit linked to a galactose-binding lectin B subunit to allow cell surface binding and toxin entry in most mammalian cells, shows a potency in the picomolar range. The most promising way to exploit plant RIPs as weapons against cancer cells is either by designing molecules in which the toxic domains are linked to selective tumor targeting domains or directly delivered as suicide genes for cancer gene therapy. Here, we will provide a comprehensive picture of plant RIPs and discuss successful designs and features of chimeric molecules having therapeutic potential.
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