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

J 2019

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

MALINOVSKÁ, Lenka, Son THAI LE, Mihály HERCZEG, Michaela VAŠKOVÁ, Josef HOUSER et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10400 1.4 Chemical sciences

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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 project

Name: Lektiny a jejich úloha v interakci patogen/hostitel a buněčném rozpoznávání

Investor: Czech Science Foundation

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

LTC17076, research and development project

Name: 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

90043, large research infrastructures

Name: CIISB

Citovat

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.

@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 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. \textit{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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