4. CARBON NANOSTRUCTURES AS BIOMOLECULES
4.1. Glycofullerenes for emergent viruses
Our group is currently engaged in a research line to explore the potential biological and pharmacological properties of fullerenes, in particular in the area of emergent viruses. Several glycofullerenes bearing different number of carbohydrates as ligands have been synthesized by using a click chemistry CuAAC methodology. Glycofullerenes, and especially fullerene hexakis-adducts substituted in a globular fashion with carbohydrates, inhibit the infection by an artificial Ebola virus in a multivalent way. Among them, glycoderivatives of tridecafullerenes, in which a central [60]fullerene core is surrounded by other twelve [60]fullerene moieties, are the most efficient inhibitors of DC-SIGN mediated Ebola virus infection, with IC50 values in the subnanomolar range (IC50 ~ 0.66 nM).
Tridecafullerenes are giant multivalent [60]fullerene derivatives which efficiently inhibit infection by an artificial Ebola virus.
To improve the synthetic methodology, we have designed new multivalent platforms based on [60]fullerene for the use of copper-free click chemistry reactions, as SPAAC or thiol-maleimide Michael addition. Thus, employing a cyclooctyne functionalized hexakis adduct of [60]fullerene and a SPAAC strategy, we have synthesized a tridecafullerene with up to 360 disaccharides. This compound has been tested against Zika and Dengue viruses infections, showing IC50 values in the picomolar range!
4.2. Carbon Nanostructures for Bio-Medical applications
Different carbon nanoforms, SWCNTs, MWCNTs and SWCNHs have also been employed as virus mimicking nanocarbon platforms for the multivalent presentation of carbohydrates, and the resulting materials have been tested against Ebola virus infection. These carbon nanoforms have been chemically modified by the covalent attachment of glycodendrons and glycofullerenes using the CuAAC approach. This modification dramatically increases the water solubility of these structurally different nanocarbons. Their efficiency to block DC-SIGN mediated viral infection by an artificial Ebola virus has proved that glycoconjugates based on MWCNTs functionalized with glycofullerenes are potent inhibitors of viral infection, being appealing carbon-based scaffolds for biomedical applications.
Three types of carbon nanotubes, SWCNTs, MWCNTs and SWCNHs have been studied as platforms for the multivalent presentation of carbohydrates. Representative TEM micrographs of SWCNHs modified with glycofullerenes.