Selectivity of original C-hexopyranosyl calix[4]arene conjugates towards lectins of different origin

Kašáková, Martina; Malinovská, Lenka; Klejch, Tomáš; Hlaváčková, Martina; Dvořáková, Hana; Fujdiarová, Eva; Rottnerová, Zdeňka; Maťátková, Olga; Lhoták, Pavel; Wimmerová, Michaela; Moravcová, Jitka

doi:10.1016/j.carres.2018.08.012

Cited by 14 publications

(13 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They are derived either from fucose or mannose (reviewed recently in [12]) and could be effective on BC2L-C. Nevertheless, to date only C-fucosides-calix [4]arene (1-3-alternate) have been tested on BC2L-C [33]. This inhibitor is able to crosslink B. cenocepacia cells and inhibits BC2L-C-induced hemagglutination.…”

Section: Discussionmentioning

confidence: 99%

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

2020

View full text Add to dashboard Cite

Lectins mediate adhesion of pathogens to host tissues, filling in a key role in the first steps of infection. Belonging to the opportunistic pathogen Burkholderia cenocepacia, BC2L-C is a superlectin with dual carbohydrate specificity, believed to mediate cross-linking between bacteria and host cells. Its C-terminal domain binds to bacterial mannosides while its N-terminal domain (BCL2-CN) recognizes fucosylated human epitopes. BC2L-CN presents a tumor necrosis factor alpha (TNF-α) fold previously unseen in lectins with a novel fucose binding mode. We report, here, the production of a novel recombinant form of BC2L-CN (rBC2L-CN2), which allowed better protein stability and unprecedented co-crystallization with oligosaccharides. Isothermal calorimetry measurements showed no detrimental effect on ligand binding and data were obtained on the binding of Globo H hexasaccharide and l-galactose. Crystal structures of rBC2L-CN2 were solved in complex with two blood group antigens: H-type 1 and H-type 3 (Globo H) by X-ray crystallography. They provide new structural information on the binding site, of importance for the structural-based design of glycodrugs as new antimicrobials with antiadhesive properties.

show abstract

Section: Discussionmentioning

confidence: 99%

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

2020

View full text Add to dashboard Cite

show abstract

“…The subsequent adhesion of bacterial clusters to the epithelial cells resulted in an increased fluorescence signal. Cross-linking of bacterial cells by multivalent carbohydrate-based compounds has been reported previously [17]. In contrast to the low inhibitory activity against lectin PA-IIL observed in vitro by a hemagglutination inhibition assay, the results obtained on a cell-cell level indicate that compound 2 has the potential to reduce the interactions of P. aeruginosa with epithelial cells of humans suffering from cystic fibrosis.…”

Section: Resultsmentioning

confidence: 84%

“…These data may suggest that BC2L-C does not employ a strong avidity effect during interaction. However, as previously tested C-hexopyranosyl calix[4]arene-based inhibitors displayed up to a 256-fold increase in inhibitory potency compared to monovalent l -fucose [17], the currently used multivalent inhibitors may be simply unable to bind to several binding sites simultaneously and further optimization will be necessary. Nevertheless, the tetravalent α- O -glycoside 2 with terminal l -fucose with longer spacers surprisingly proved to be the best inhibitor of all lectins used in this study.…”

Section: Resultsmentioning

confidence: 99%

“…The known multivalent inhibitors of AFL include cyclopeptide-based hexavalent compounds with a terminal fucose residue and multivalent compounds based on cyclodextrin or octameric silsesquioxane scaffolds [15,16]. C-hexopyranosyl calix[4]arene conjugates were used as potential multivalent inhibitors of BC2L-C and AFL [17]. A broad variety of potential monovalent and multivalent inhibitors were designed and tested against PA-IIL, including C-glycosidic glycomimetics, cinnamide and sulfonamide carbohydrate derivatives, fucofullerenes, glycopeptide dendrimers, pentavalent pillar[5]arene-based glycoclusters, perylenediimide-based glycoclusters, and photoswitchable Janus glycodendrimer micelles [18,19,20,21,22,23,24].…”

Section: Introductionmentioning

confidence: 99%

“…A broad variety of potential monovalent and multivalent inhibitors were designed and tested against PA-IIL, including C-glycosidic glycomimetics, cinnamide and sulfonamide carbohydrate derivatives, fucofullerenes, glycopeptide dendrimers, pentavalent pillar[5]arene-based glycoclusters, perylenediimide-based glycoclusters, and photoswitchable Janus glycodendrimer micelles [18,19,20,21,22,23,24]. Fucofullerenes and C-hexopyranosyl calix[4]arene conjugates were examined as potential multivalent inhibitors of RSL [17,18,19,20].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Investigation of the Binding Affinity of a Broad Array of l-Fucosides with Six Fucose-Specific Lectins of Bacterial and Fungal Origin

Malinovská

Vašková

et al. 2019

Molecules

Self Cite

View full text Add to dashboard Cite

Series of multivalent α-l-fucoside containing glycoclusters and variously decorated l-fucosides were synthesized to find potential inhibitors of fucose-specific lectins and study the structure-binding affinity relationships. Tri- and tetravalent fucoclusters were built using copper-mediated azide-alkyne click chemistry. Series of fucoside monomers and dimers were synthesized using various methods, namely glycosylation, an azide-alkyne click reaction, photoinduced thiol-en addition, and sulfation. The interactions between compounds with six fucolectins of bacterial or fungal origin were tested using a hemagglutination inhibition assay. As a result, a tetravalent, α-l-fucose presenting glycocluster showed to be a ligand that was orders of magnitude better than a simple monosaccharide for tested lectins in most cases, which can nominate it as a universal ligand for studied lectins. This compound was also able to inhibit the adhesion of Pseudomonas aeruginosa cells to human epithelial bronchial cells. A trivalent fucocluster with a protected amine functional group also seems to be a promising candidate for designing glycoconjugates and chimeras.

show abstract

Targeting Bacterial Biofilm: A New LecA Multivalent Ligand with Inhibitory Activity

2019

View full text Add to dashboard Cite

Biofilm formation by bacterial pathogens is a hallmark of chronic infections and is associated to increased antibiotic tolerance that makes pathogens difficult to eradicate with conventional antibiotic therapies. Infections caused by Pseudomonas aeruginosa are of great concern, especially for immunocompromised and cystic fibrosis patients. P. aeruginosa lectins LecA and LecB are virulence factors and play a key role in establishing biofilm; therefore, inhibition of the function of these proteins has potential in dismantling the bacterium from the protective biofilm environment and in restoring the activity of antibiotics. Here, we report the NMR characterization of the binding of a galactose‐based dendrimer (Gal18) to LecA. Moreover, we demonstrate the activity of the Gal18 molecule in inhibiting P. aeruginosa biofilm formation in vitro.

show abstract

Selectivity of original C-hexopyranosyl calix[4]arene conjugates towards lectins of different origin

Cited by 14 publications

References 62 publications

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

Investigation of the Binding Affinity of a Broad Array of l-Fucosides with Six Fucose-Specific Lectins of Bacterial and Fungal Origin

Targeting Bacterial Biofilm: A New LecA Multivalent Ligand with Inhibitory Activity

Contact Info

Product

Resources

About