A variety of different chemical and bio-inspired scaffolds have previously been used in the search for new glycoconjugates bearing the carbohydrates located in the appropriate spatial arrangement. Actually, there are a many examples where multivalency drastically enhances the interactions between biomolecules in comparison to the analogous monovalent binding.

In order to design multivalent peripheral ligands with glycomimetic properties that structurally can attach to the receptor sites of complex biological structures, a broad variety of ‘‘artificial glycoforms’’ have been created to study and understand the mechanisms involved in multivalent binding interactions. In this regard, we have recently shown that hexakis-adducts of [60]fullerene endowed with 12, 24 or 36 mannoses, act as strong inhibitors for DC-SIGN in an Ebola infection assay model.¹ Furthermore, a drastic increase in the inhibition process at the subnanomolar scale has been observed when the size and mannoses´ number are increased in the firstly reported tridecafullerenes endowed with 120 mannose units decorating the periphery of the molecule.²

From the work carried out by our group on glycofullerenes with globular symmetry, it is possible to bring to light the significance of size and shape of the glycomimetic, being even more determinant that the number of carbohydrate moieties in the glycoparticle.

In the present work, the synthetic approach is simplified, using C₆₀ mono-adducts instead of C₆₀ hexakis-adducts, without compromising the spherical form of the final glycomimetic, provided by the supramolecular aggregate resulting from the self-assembly of mono-adducts.³ The efficiency to block DC-SIGN mediated viral infection by an artificial Ebola virus has been tested in a cellular experimental assay finding that, these systems are potent inhibitors of viral infection.

References

1. a) B. M. Illescas, J. Rojo, R. Delgado, N. Martín, "Multivalent Glycosylated Nanostructures To Inhibit Ebola Virus Infection" J. Am. Chem. Soc., 2017, 139, 6018−6025; b) J. Luczkowiak, A. Muñoz, M. Sánchez-Navarro, R. Ribeiro-Viana, A. Ginieis, B. M. Illescas, N. Martín, R. Delgado, J. Rojo, Biomacromolecules 2013, 14, 431-437; c) J.-F. Nierengarten, J. Iehl, V. Oerthel, M. Holler, B. M. Illescas, A. Muñoz, N. Martín, J. Rojo, M. Sánchez-Navarro, S. Cecioni, S. Vidal, K. Buffet, M. Durka, S. P. Vincent, Chem. Commun. 2010, 46, 3860-3862; d) M. Sánchez-Navarro, A. Muñoz, B. M. Illescas, J. Rojo, N. Martín, Chem. Eur. J. 2011, 17, 766-769.
2. A. Muñoz, D. Sigwalt, B. M. Illescas, J. Luczkowiak, L. Rodríguez, I. Nierengarten, M. Holler, J.-S. Remy, K. Buffet, S. P. Vincent, J. Rojo, R. Delgado, J.-F. Nierengarten, N. Martín, Nat. Chem., 2016, 8, 50-57.
3. A. Muñoz, B. M. Illescas, J. Luczkowiak, F. Lasala, R. Ribeiro-Viana, J. Rojo, R. Delgado, N. Martín, J. Mater. Chem. B, 2017, 5, 6566-6571.