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@article{1587678,
author = {Malinovská, Lenka and Thai Le, Son and Herczeg, Mihály and Vašková, Michaela and Houser, Josef and Fujdiarová, Eva and Komárek, Jan and Hodek, Petr and Borbás, Anikó and Wimmerová, Michaela and Csávás, Magdolna},
article_number = {11},
doi = {http://dx.doi.org/10.3390/biom9110686},
keywords = {Pseudomonas aeruginosa; cystic fibrosis; lectin; D-galactosides; multivalency},
language = {eng},
issn = {2218-273X},
journal = {Biomolecules},
title = {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},
url = {https://www.mdpi.com/2218-273X/9/11/686},
volume = {9},
year = {2019}
}
TY - JOUR
ID - 1587678
AU - Malinovská, Lenka - Thai Le, Son - Herczeg, Mihály - Vašková, Michaela - Houser, Josef - Fujdiarová, Eva - Komárek, Jan - Hodek, Petr - Borbás, Anikó - Wimmerová, Michaela - Csávás, Magdolna
PY - 2019
TI - 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
JF - Biomolecules
VL - 9
IS - 11
SP - 686
EP - 686
PB - MDPI
SN - 2218273X
KW - Pseudomonas aeruginosa
KW - cystic fibrosis
KW - lectin
KW - D-galactosides
KW - multivalency
UR - https://www.mdpi.com/2218-273X/9/11/686
L2 - https://www.mdpi.com/2218-273X/9/11/686
N2 - 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
ER -
MALINOVSKÁ, Lenka, Son THAI LE, Mihály HERCZEG, Michaela VAŠKOVÁ, Josef HOUSER, Eva FUJDIAROVÁ, Jan KOMÁREK, Petr HODEK, Anikó BORBÁS, Michaela WIMMEROVÁ a Magdolna CSÁVÁS. 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. \textit{Biomolecules}. MDPI, 2019, roč.~9, č.~11, s.~686-707. ISSN~2218-273X. Dostupné z: https://dx.doi.org/10.3390/biom9110686.
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