Multivalent Tryptophan‐ and Tyrosine‐Containing [60]Fullerene Hexa‐Adducts as Dual HIV and Enterovirus A71 Entry Inhibitors

Abstract

Unprecedented 3D hexa-adducts of [60]fullerene peripherally decorated with twelve tryptophan (Trp) or tyrosine (Tyr) residues have been synthesized. Studies on the antiviral activity of these novel compounds against HIV and EV71 reveal that they are much more potent against HIV and equally active against EV71 than the previously described dendrimer prototypes AL-385 and AL-463, which possess the same number of Trp/Tyr residues on the periphery but attached to a smaller and more flexible pentaerythritol core. These results demonstrate the relevance of the globular 3D presentation of the peripheral groups (Trp/Tyr) as well as the length of the spacer connecting them to the central core to interact with the viral envelopes, particularly in the case of HIV, and support the hypothesis that [60]fullerene can be an alternative and attractive biocompatible carbon-based scaffold for this type of highly symmetrical dendrimers. In addition, the functionalized fullerenes here described, which display twelve peripheral negatively charged indole moieties on their globular surface, define a new and versatile class of compounds with a promising potential in biomedical applications.

Synthesis of an Azide- and Tetrazine-Functionalized [60]Fullerene and Its Controlled Decoration with Biomolecules

“…In conclusion, a bifunctional C 60 core ( 1 ) has been described, which can be selectively functionalized by two subsequent pericyclic click reactions (iEDDA and SPAAC) in catalyst-free conditions. The applicability of the core in a one-pot assembly has been demonstrated for the synthesis of heteroantennary glycoballs (and one glyco-peptide C 60 -conjugate , ) C4 – C7 , which were obtained in 56–69% isolated yields. Furthermore, a novel type SNA ( C9 ) with extraordinary stable covalently bound double helices, verified by UV- and CD-melting profile experiments, has been assembled in 29% overall yield.…”

Synthesis and biological application of glyco- and peptide derivatives of fullerene C60

“…Cycloaddition is not the only way to obtain amino acids or peptides derivatives, indeed another approach involves nucleophilic addictions.Bingel belongs to this class of reactions, Ruiz-Santaquiteria et al [73] exploited it to obtain a hexa-adduct fullerene containing tryptophane or tyrosine (Scheme 8A).…”

Topological and Multivalent Effects in Glycofullerene Oligomers as EBOLA Virus Inhibitors

“…In this regard, during the last years different studies have revealed important antiviral activity developed by [60]fullerene derivatives. In particular, by hexakis-adducts of [60]fullerene highly derivatized with biomolecules such as carbohydrates [ 6 , 7 , 8 , 9 , 10 ] and amino acids [ 11 ]. These hexakis-adducts present icosahedral geometry, are soluble in biological media, and are not cytotoxic.…”