Bispecific Thio-linked Disaccharides as Inhibitors of
Pseudomonas aeruginosa Lectins LecA (PA-IL) and LecB (PA-IIL):
Dual-Targeting Strategy

J 2025

Bispecific Thio-linked Disaccharides as Inhibitors of Pseudomonas aeruginosa Lectins LecA (PA-IL) and LecB (PA-IIL): Dual-Targeting Strategy

FALTINEK, Lukáš, Filip MELICHER, Viktor KELEMEN, Erika MEZŐ, Anikó BORBÁS et. al.

Základní údaje

Originální název

Bispecific Thio-linked Disaccharides as Inhibitors of Pseudomonas aeruginosa Lectins LecA (PA-IL) and LecB (PA-IIL): Dual-Targeting Strategy

Název česky

Bispecifické thio-vázané disacharidy jako inhibitory lektinů Pseudomonas aeruginosa LecA (PA-IL) a LecB (PA-IIL): Strategie dvojitého cílení

Autoři

FALTINEK, Lukáš (203 Česká republika, domácí), Filip MELICHER (703 Slovensko, domácí), Viktor KELEMEN (348 Maďarsko), Erika MEZŐ (348 Maďarsko), Anikó BORBÁS (348 Maďarsko) a Michaela WIMMEROVÁ (203 Česká republika, garant, domácí)

Vydání

Chemistry – A European Journal, Wiley, 2025, 0947-6539

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10400 1.4 Chemical sciences

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Full text

Impakt faktor

Impact factor: 3.900 v roce 2023

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1002/chem.202403546

UT WoS

001365219400001

Klíčová slova česky

lektiny; Pseudomonas aeruginosa; syntetické sacharidy; inhibice; aglutinace

Klíčová slova anglicky

lectins; Pseudomonas aeruginosa; synthetic carbohydrates; inhibition; agglutination

Štítky

CF BIC, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 17. 3. 2025 10:06, Mgr. Eva Dubská

Anotace

V originále

Pseudomonas aeruginosa is a prevalent opportunistic human pathogen, particularly associated with cystic fibrosis. Among its virulence factors are the LecA and LecB lectins. Both lectins play an important role in the adhesion to the host cells and display cytotoxic activity. In this study, we successfully synthesized hardly hydrolysable carbohydrate ligands targeting these pathogenic lectins, including two bispecific glycans. The interactions between LecA/LecB lectins and synthetic glycans were evaluated using hemagglutination (yeast agglutination) inhibition assays, comparing their efficacy with corresponding monosaccharides. Additionally, the binding affinities of bispecific glycans were assessed using isothermal titration calorimetry (ITC). Structural insight into the lectin-ligand interaction was obtained by determining the crystal structures of LecA/LecB lectins in complex with one of the bispecific ligands using X ray crystallography. This comprehensive investigation into the inhibitory potential of synthetic glycosides against P. aeruginosa lectins sheds light on their potential application in antimicrobial therapy.

Návaznosti

EF18_046/0015974, projekt VaV

Název: Modernizace České infrastruktury pro integrativní strukturní biologii

GA21-29622S, projekt VaV

Název: Biologická úloha lektinů v symbióze a patogenezi

Investor: Grantová agentura ČR, Biologická úloha lektinů v symbióze a patogenezi

90242, velká výzkumná infrastruktura

Název: CIISB III

Citovat

FALTINEK, Lukáš, Filip MELICHER, Viktor KELEMEN, Erika MEZŐ, Anikó BORBÁS a Michaela WIMMEROVÁ. Bispecific Thio-linked Disaccharides as Inhibitors of Pseudomonas aeruginosa Lectins LecA (PA-IL) and LecB (PA-IIL): Dual-Targeting Strategy. Chemistry – A European Journal. Wiley, 2025, roč. 31, č. 5, s. 1-10. ISSN 0947-6539. Dostupné z: https://dx.doi.org/10.1002/chem.202403546.

@article{2455557,
   author = {Faltinek, Lukáš and Melicher, Filip and Kelemen, Viktor and Mező, Erika and Borbás, Anikó and Wimmerová, Michaela},
   article_number = {5},
   doi = {http://dx.doi.org/10.1002/chem.202403546},
   keywords = {lectins; Pseudomonas aeruginosa; synthetic carbohydrates; inhibition; agglutination},
   language = {eng},
   issn = {0947-6539},
   journal = {Chemistry – A European Journal},
   title = {Bispecific Thio-linked Disaccharides as Inhibitors of Pseudomonas aeruginosa Lectins LecA (PA-IL) and LecB (PA-IIL): Dual-Targeting Strategy},
   url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202403546},
   volume = {31},
   year = {2025}
}

TY  - JOUR
ID  - 2455557
AU  - Faltinek, Lukáš - Melicher, Filip - Kelemen, Viktor - Mező, Erika - Borbás, Anikó - Wimmerová, Michaela
PY  - 2025
TI  - Bispecific Thio-linked Disaccharides as Inhibitors of Pseudomonas aeruginosa Lectins LecA (PA-IL) and LecB (PA-IIL): Dual-Targeting Strategy
JF  - Chemistry – A European Journal
VL  - 31
IS  - 5
SP  - 1-10
EP  - 1-10
PB  - Wiley
SN  - 09476539
KW  - lectins
KW  - Pseudomonas aeruginosa
KW  - synthetic carbohydrates
KW  - inhibition
KW  - agglutination
UR  - https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202403546
N2  - Pseudomonas aeruginosa is a prevalent opportunistic human pathogen, particularly associated with cystic fibrosis. Among its virulence factors are the LecA and LecB lectins. Both lectins play an important role in the adhesion to the host cells and display cytotoxic activity. In this study, we successfully synthesized hardly hydrolysable carbohydrate ligands targeting these pathogenic lectins, including two bispecific glycans. The interactions between LecA/LecB lectins and synthetic glycans were evaluated using hemagglutination (yeast agglutination) inhibition assays, comparing their efficacy with corresponding monosaccharides. Additionally, the binding affinities of bispecific glycans were assessed using isothermal titration calorimetry (ITC). Structural insight into the lectin-ligand interaction was obtained by determining the crystal structures of LecA/LecB lectins in complex with one of the bispecific ligands using X ray crystallography. This comprehensive investigation into the inhibitory potential of synthetic glycosides against P. aeruginosa lectins sheds light on their potential application in antimicrobial therapy.
ER  -

FALTINEK, Lukáš, Filip MELICHER, Viktor KELEMEN, Erika MEZ$\backslash$H O, Anikó BORBÁS a Michaela WIMMEROVÁ. Bispecific Thio-linked Disaccharides as Inhibitors of Pseudomonas aeruginosa Lectins LecA (PA-IL) and LecB (PA-IIL): Dual-Targeting Strategy. \textit{Chemistry – A European Journal}. Wiley, 2025, roč.~31, č.~5, s.~1-10. ISSN~0947-6539. Dostupné z: https://dx.doi.org/10.1002/chem.202403546.

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