The functional valency of dodecamannosylated fullerenes with Escherichia coli FimH—towards novel bacterial antiadhesives

Abstract

Fullerene hexakis-adducts bearing 12 peripheral mannose moieties have been prepared by grafting sugar derivatives onto the fullerene core and assayed as inhibitors of FimH, a bacterial adhesin, using isothermal titration calorimetry, surface plasmon resonance and hemagglutination assays.

Glycodendrimers: versatile tools for nanotechnology

“…The best candidate 38, with an HAI titer of 1 μM, showed a 32-fold better binding affinity when corrected on a per mannoside residue. This value compares favorably well with the ones recently published using fullerene (Durka et al, 2011) or pentaerythritol (Gouin et al, 2009 scaffolds. However, a linear heptameric mannocluster built on sugar scaffolds and having a more hydrophobic heptyl aglycon showed better HAI titers than the one reported herein (Almant et al, 2011).…”

Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

“…28,29 The composition of compounds 17b and 17c has also been ascertained by their respective XPS analyses which showed the presence of the expected elements, according to their relative abundance (see Supplementary Figure 4 Previous inhibition studies using the same infection model and fullerenes displaying up to 36 mannoses show relative inhibitor potency (RIP) values at least two orders of magnitude smaller. 19 Moreover, huge virus-like particles (VLP) with a radius of 16 nm and up to 1640 mannoses 33 were 18 fold less potent than compound 17c described in this work (see Supplementary Table 2). These results have confirmed the efficiency of these systems to interact with DC-SIGN and to compete with Ebola virus glycoprotein-pseudotyped particles during their entry into target cells.…”

“…16 On the other hand, fullerene hexakis-adducts bearing 12 mannoses on the periphery behave as inhibitors of FimH, a bacterial adhesin. 19 Furthermore, studies carried out on hexakis-adducts of [60]fullerene endowed with 12, 24 and 36 mannoses have shown a multivalent effect in the interaction with Concanavalin A, 15 and acting as efficient inhibitors of cell infection by Ebola pseudotyped viral particles. 20 These preliminary studies reveal that fullerenes are adequate platforms for the multivalent presentation of carbohydrates, thus paving the way to the covalent linkage of a wide variety of different bio-active molecules in a multivalent manner and a singular and less-explored globular topology.…”

Glycoconjugates and Glycomimetics as Microbial Anti-Adhesives

“…against gut-colonizing AIEC), or when FimH adhesion is exploited to achieve bacterial aggregation and biofilm disruption. They vary from medium-sized scaffolds [19][20][21][22][23], to dendrimers [3,24], polymers [25] and nanoparticles [26][27][28][29]. Despite the spacing between fimbriae can vary between strains and depends on growth conditions [30], only the largest of these materials are likely to engage more than one protein at the time, because the FimH binding site can interact with only one mannose residue at the time and each of the fimbriae carries only a single copy of FimH.…”