Blood–brain barrier shuttle peptides are increasingly more potent and versatile tools to enhance drug delivery to the brain.

Fullerene hexakis-adducts bearing 12 peripheral carbohydrate moieties have been prepared by grafting sugar derivatives onto the fullerene core through the copper mediated Huisgen 1,3-dipolar cycloaddition of azides and alkynes.

Ligand polyvalency is a powerful modulator of protein–receptor interactions. Host–pathogen infection interactions are often mediated by glycan ligand–protein interactions, yet its interrogation with very high copy number ligands has been limited to heterogenous systems. Here we report that through the use of nested layers of multivalency we are able to assemble the most highly valent glycodendrimeric constructs yet seen (bearing up to 1,620 glycans). These constructs are pure and well-defined single entities that at diameters of up to 32 nm are capable of mimicking pathogens both in size and in their highly glycosylated surfaces. Through this mimicry these glyco-dendri-protein-nano-particles are capable of blocking (at picomolar concentrations) a model of the infection of T-lymphocytes and human dendritic cells by Ebola virus. The high associated polyvalency effects (β>10⁶, β/N ~10²–10³) displayed on an unprecedented surface area by precise clusters suggest a general strategy for modulation of such interactions.

The free-radical hydrothiolation of alkynes (thiol-yne coupling, TYC) unites two thiol fragments across the carbon-carbon triple bond to give a dithioether derivative with exclusive 1,2-addition; this reaction can be used for modification of peptides and proteins allowing glycoconjugation and fluorescent labeling. These results have implications not only as a flexible strategy for attaching two modifications at a single site in proteins but also for unanticipated side-reactions of reagents (such as cycloalkynes) used in other protein coupling reactions.