MALINOVSKÁ, Lenka, Son THAI LE, Mihály HERCZEG, Michaela VAŠKOVÁ, Josef HOUSER, Eva FUJDIAROVÁ, Jan KOMÁREK, Petr HODEK, Anikó BORBÁS, Michaela WIMMEROVÁ and 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. Biomolecules. MDPI, 2019, vol. 9, No 11, p. 686-707. ISSN 2218-273X. Available from: https://dx.doi.org/10.3390/biom9110686.
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Basic information
Original name 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
Authors MALINOVSKÁ, Lenka (203 Czech Republic, belonging to the institution), Son THAI LE, Mihály HERCZEG (348 Hungary), Michaela VAŠKOVÁ (203 Czech Republic), Josef HOUSER (203 Czech Republic, belonging to the institution), Eva FUJDIAROVÁ (203 Czech Republic, belonging to the institution), Jan KOMÁREK (203 Czech Republic, belonging to the institution), Petr HODEK (203 Czech Republic), Anikó BORBÁS (348 Hungary), Michaela WIMMEROVÁ (203 Czech Republic, guarantor, belonging to the institution) and Magdolna CSÁVÁS (348 Hungary).
Edition Biomolecules, MDPI, 2019, 2218-273X.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10400 1.4 Chemical sciences
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 4.082
RIV identification code RIV/00216224:14740/19:00107833
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.3390/biom9110686
UT WoS 000502267900047
Keywords in English Pseudomonas aeruginosa; cystic fibrosis; lectin; D-galactosides; multivalency
Tags CF BIC, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 31/3/2020 21:56.
Abstract
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
Links
GA18-18964S, research and development projectName: Lektiny a jejich úloha v interakci patogen/hostitel a buněčném rozpoznávání
Investor: Czech Science Foundation
LM2015043, research and development projectName: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)
Investor: Ministry of Education, Youth and Sports of the CR
LQ1601, research and development projectName: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR
LTC17076, research and development projectName: Interdisciplinární přístup ke studiu biologických systémů na molekulární úrovni
Investor: Ministry of Education, Youth and Sports of the CR, Interdisciplinary approach to study biological systems at the molecular level, INTER-COST
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