RT Journal Article
T1 Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection
A1 Muñoz, Antonio
A1 Sigwalt, David
A1 Illescas Martínez, Beatriz María
A1 Luczkowiak, Joana
A1 Rodríguez, Laura
A1 Nierengarten, Iwona
A1 Holler, Michel
A1 Remy, Jean Serge
A1 Buffet, Kevin
A1 Vincent, Stéphane P.
A1 Rojo, Javier
A1 Delgado Vázquez, Rafael
A1 Nierengarten, Jean-Françoise
A1 Martín León, Nazario
AB 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.
PB Nature Publishing Group
SN 1755-4330
YR 2016
FD 2016-01
LK https://hdl.handle.net/20.500.14352/23168
UL https://hdl.handle.net/20.500.14352/23168
LA eng
NO Muñoz, A., Sigwalt, D., Illescas Martínez, B. M. et al. «Synthesis of Giant Globular Multivalent Glycofullerenes as Potent Inhibitors in a Model of Ebola Virus Infection». Nature Chemistry, vol. 8, n.o 1, enero de 2016, pp. 50-57. DOI.org (Crossref), https://doi.org/10.1038/nchem.2387.
NO Unión Europea
NO Ministerio de Economía, Comercio y Empresa (España)
NO Comunidad Autónoma de Madrid
NO Instituto de Salud Carlos III
NO Agence Nationale de la Recherche (Francia)
DS Docta Complutense
RD 9 abr 2025