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Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

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Muñoz, Antonio and Sigwalt, David and Illescas, Beatriz M. and Luczkowiak, Joana and Rodríguez, Laura and Nierengarten, Iwona and Holler, Michel and Remy, Jean Serge and Buffet, Kevin and Vincent, Stéphane P. and Rojo, Javier and Delgado, Rafael and Nierengarten, Jean-Françoise and Martín, Nazario (2016) Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection. Nature Chemistry, 8 . pp. 50-57. ISSN ISSN: 1755-4330 EISSN: 1755-4349

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Official URL: http://www.nature.com/nchem/journal/v8/n1/full/nchem.2387.html



Abstract

The inhibition of pathogens entry through the blockade of DC-SIGN (dendritic cell-specific intercelular adhesion molecule-3-grabbing nonintegrin) receptor at early stages of infection is an efficient strategy for testing new antiviral agents. Although a variety of models have been reported, one of the main problems is achieving adequate size and multivalency to mimic natural systems such as viruses or other pathogens. In this regard, hexakis-adducts of [60]fullerene allow a full control of size and multivalency while maintaining a globular shape. For this purpose,tridecafullerenes decorated with 120 peripheral carbohydrate subunits have been efficiently synthesized from hexakis-adducts of [60]fullerene in one synthetic step by using the copper-catalyzed azide–alkyne cycloaddition (CuAAC) click-chemistry methodology. These so-called 'superballs' decorated with 120 mono-saccharides (mannose or galactose) moieties are water soluble, allowing the study of their biological properties. An infection assay has been employed to test the ability of these compounds to inhibit the infection of cells by an artificial Ebola virus. The results obtained in these experiments show that the 'superballs' are potent inhibitors of cell infection by this artificial Ebola virus with IC50s in the sub-nanomolar range. This implies more than a three-orders-of-magnitude increase of activity in comparison to the hexakis-adduct containing just 12 mannoses and only 18-fold less activity than virus-like glycodendrinanoparticles with diameters of roughly 32 nm displaying up to 1620 glycans.


Item Type:Article
Uncontrolled Keywords:antivirus agent; azide; fullerene derivative; glycoconjugate; mannose
Subjects:Sciences > Chemistry > Chemistry, Organic
ID Code:41690
Deposited On:07 Mar 2017 12:24
Last Modified:07 Mar 2017 12:43

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