Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection
Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection
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DOI：
10.1038/nchem.2387
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发表时间：
2016-01-01
期刊：
影响因子：
21.8
通讯作者：
Martin, Nazario
中科院分区：
文献类型：
--
作者：
Munoz, Antonio;Sigwalt, David;Martin, Nazario
使用多价碳水化合物来阻断细胞表面凝集素受体是抑制病原体进入细胞的一种有前途的策略，并可能导致新的抗病毒剂的发现。然而，这种方法的主要问题之一是，很难制造足够大小和多价的化合物来模拟自然系统，如病毒。[60]富勒烯的六方加合物在这方面是有用的结构单元，因为它们保持球形，同时允许控制大小和多价性。在这里，我们报告了水溶性十三碳富勒烯装饰与120个外围碳水化合物亚基，所谓的“超级球”，可以有效地合成从[60]富勒烯的hexakis加合物在一个步骤中通过使用铜催化的叠氮化物-炔环加成点击化学。感染试验表明，这些超级球是人工埃博拉病毒感染细胞的有效抑制剂，半最大抑制浓度在亚纳摩尔范围内。
The use of multivalent carbohydrate compounds to block cell-surface lectin receptors is a promising strategy to inhibit the entry of pathogens into cells and could lead to the discovery of novel antiviral agents. One of the main problems with this approach, however, is that it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses. Hexakis adducts of [60] fullerene are useful building blocks in this regard because they maintain a globular shape at the same time as allowing control over the size and multivalency. Here we report water-soluble tridecafullerenes decorated with 120 peripheral carbohydrate subunits, so-called 'superballs', that can be synthesized efficiently from hexakis adducts of [60] fullerene in one step by using copper-catalysed azide-alkyne cycloaddition click chemistry. Infection assays show that these superballs are potent inhibitors of cell infection by an artificial Ebola virus with half-maximum inhibitory concentrations in the subnanomolar range.