Informace o publikaci

Synthesis of beta-D-galactopyranoside-Presenting Glycoclusters, Investigation of Their Interactions with Pseudomonas aeruginosa Lectin A (PA-IL) and Evaluation of Their Anti-Adhesion Potential

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MALINOVSKÁ Lenka THAI LE Son HERCZEG Mihály VAŠKOVÁ Michaela HOUSER Josef FUJDIAROVÁ Eva KOMÁREK Jan HODEK Petr BORBÁS Anikó WIMMEROVÁ Michaela CSÁVÁS Magdolna

Rok publikování 2019
Druh Článek v odborném periodiku
Časopis / Zdroj Biomolecules
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www https://www.mdpi.com/2218-273X/9/11/686
Doi http://dx.doi.org/10.3390/biom9110686
Klíčová slova Pseudomonas aeruginosa; cystic fibrosis; lectin; D-galactosides; multivalency
Popis Pseudomonas aeruginosa is an opportunistic human pathogen associated with cystic fibrosis. This bacterium produces, among other virulence factors, a soluble D-galactose-specific lectin PA-IL (LecA). PA-IL plays an important role in the adhesion to the host cells and is also cytotoxic. Therefore, this protein is an interesting therapeutic target, suitable for inhibition by carbohydrate-based compounds. In the current study, beta-D-galactopyranoside-containing tri- and tetravalent glycoclusters were synthesized. Methyl gallate and pentaerythritol equipped with propargyl groups were chosen as multivalent scaffolds and the galactoclusters were built from the above-mentioned cores by coupling ethylene or tetraethylene glycol-bridges and peracetylated propargyl beta-D-galactosides using 1,3-dipolar azide-alkyne cycloaddition. The interaction between galactoside derivatives and PA-IL was investigated by several biophysical methods, including hemagglutination inhibition assay, isothermal titration calorimetry, analytical ultracentrifugation, and surface plasmon resonance. Their ability to inhibit the adhesion of P. aeruginosa to bronchial cells was determined by ex vivo assay. The newly synthesized multivalent galactoclusters proved to be significantly better ligands than simple d-galactose for lectin PA-IL and as a result, two representatives of the dendrimers were able to decrease adhesion of P. aeruginosa to bronchial cells to approximately 32% and 42%, respectively. The results may provide an opportunity to develop anti-adhesion therapy for the treatment of P. aeruginosa infection
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