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The synthesis of pillar[5]arene-based glycoclusters has been readily achieved by CuAAC conjugations of azido- and alkyne-functionalized precursors. The lectin binding properties of the resulting glycosylated multivalent ligands have been studied by at least two complementary techniques to provide a good understanding. Three lectins were selected from bacterial pathogens based on their potential therapeutic applications as anti-adhesives, namely LecA and LecB from Pseudomonas aeruginosa and BambL from Burkholderia ambifaria. As a general trend, multivalency improved the binding to lectins and a higher affinity can be obtained by increasing to a certain limit the length of the spacer arm between the carbohydrate subunits and the central macrocyclic core., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The use of multivalent carbohydrate compounds to block cell-surface lectin receptors is a promising strategy to inhibit the entry of pathogens into cells and could lead to the discovery of novel antiviral agents. One of the main problems with this approach, however, is that it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses. Hexakis adducts of [60]fullerene are useful building blocks in this regard because they maintain a globular shape at the same time as allowing control over the size and multivalency. Here we report water-soluble tridecafullerenes decorated with 120 peripheral carbohydrate subunits, so-called 'superballs', that can be synthesized efficiently from hexakis adducts of [60]fullerene in one step by using copper-catalysed azide–alkyne cycloaddition click chemistry. Infection assays show that these superballs are potent inhibitors of cell infection by an artificial Ebola virus with half-maximum inhibitory concentrations in the subnanomolar range.

Design of multivalent glycoconjugates can find applications such as in anti-adhesive therapy against bacterial infections. Nevertheless, the access to such macromolecules requires functionalized building blocks prepared in a minimum number of steps and on a multi-gram scale at least for the laboratory. Fucose is a representative epitope used by several bacteria for adhesion to their host cells. The stereoselective, rapid, and efficient access to two 'clickable' α-fucosides was re-investigated using PPh3/CBr4-promoted glycosylation of chloro- (as precursors of azido-) and alkyne-functionalized triethyleneglycols with fully unprotected l-fucose. The convenient access to such building blocks paves the way to the design of new multivalent glycoconjugates functionalized with fucose epitopes and their applications., (Copyright © 2014 Elsevier Ltd. All rights reserved.)