Cyclotriveratrylene‐Based Glycoclusters as High Affinity Ligands of Bacterial Lectins from Pseudomonas aeruginosa and Burkholderia ambifaria

Abstract

The design of multivalent glycoconjugates has been largely studied using a variety of core scaffolds. Cyclotriveratrylenes (CTV) have been scarcely used in this context. The synthesis of the tri‐ and hexa‐propargylated CTV cores allowed the preparation of the corresponding glycoclusters with galactose or fucose residues through azide‐alkyne “click” chemistry. Their interactions with bacterial lectins (LecA, LecB and BambL) was confirmed and studied by titration microcalorimetry. Adsorption onto carbon nanotubes was then attempted based on the hydrophobic CTV cores. Their incorporation into field effect transistor (FET) devices was accomplished but the data collected largely suggested a poor interaction of CTV‐based glycoclusters with the carbon nanotubes leading to non‐specific detection of the lectins.

Perylenediimide-based glycoclusters as high affinity ligands of bacterial lectins: synthesis, binding studies and anti-adhesive properties

“…35,36 We have also previously designed a large series of glycoclusters for applications in anti-adhesive strategies against P. aeruginosa infection. [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] We have especially demonstrated the excellent anti-adhesive properties of calixarene-based glycoclusters in animal models of lung infection leading to protection of mice against P. aeruginosa infection.…”

Low-Valent Calix[4]arene Glycoconjugates Based on Hydroxamic Acid Bearing Linkers as Potent Inhibitors in a Model of Ebola Virus Cis-Infection and HCMV-gB-Recombinant Glycoprotein Interaction with MDDC Cells by Blocking DC-SIGN

“…The protein surfaces in the vicinity of these Ca 2+ sites can also play a role as a secondary recognition domain; thus, small noncarbohydrate molecules, interacting with these hydrophobic surfaces, − or glycomimetic with binding affinities for Ca 2+ -dependent CRDs, have emerged as potent classes of DC-SIGN inhibitors. , An understanding of the CRD structures and their locations on protein surfaces facilitates the design of glycomimetic DC-SIGN antagonists. DC-SIGN naturally recognizes mannose- and fucose-based glycans expressed by microorganisms and on endogenous cell surfaces. , As is typical for a wide range of lectins, − DC-SIGN has only a moderate affinity for specific monovalent sugars in the millimolar range for α- d -mannose and α- l -fucose. , Inspired by nature, the use of the multivalent system that creates a strong synergistic multiple binding with lectin stands out as an obvious solution to amplify lectin/carbohydrate recognition. , Thus, antiviral therapies based on competitive multivalent DC-SIGN antagonists could counter the decreasing efficacy of existing antiviral drugs. , Examples including mannosylated scaffold-based dendrimers, , gold nanoparticles, fullerenes, , polymers, proteins, or peptides have been reported over the last 2 decades for this purpose. We have contributed by the first water-soluble calixarene- and thiacalixarene glycoclusters with pseudopeptide (PP) bearing spacer that strongly inhibits DC-SIGN in solution and cellular assays .…”

Multivalent Glycomimetics with Affinity and Selectivity toward Fucose-Binding Receptors from Emerging Pathogens

“…Fucosylated glycocluster exhibiting 4, 6, or 8 residues were synthesized based on mannose-centered and branched-phosphodiester scaffolds with best affinities of approximately 43 nM . Additionally, hexavalent cyclotriveratrylene and penta- and decavalent pillarenes , have also shown very strong affinity for BambL (ca. 20 nM).…”

“…16 branched-phosphodiester scaffolds with best affinities of approximately 43 nM. 17 Additionally, hexavalent cyclotriveratrylene 18 and penta-and decavalent pillarenes 19,20 have also shown very strong affinity for BambL (ca. 20 nM).…”