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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F25%3A00140396" target="_blank" >RIV/00216224:14310/25:00140396 - isvavai.cz</a>

Výsledek na webu

<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202403546" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202403546</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/chem.202403546" target="_blank" >10.1002/chem.202403546</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10400 - Chemical sciences

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemistry – A European Journal

ISSN

0947-6539

e-ISSN

1521-3765

Svazek periodika

31

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

10

Strana od-do

1-10

Kód UT WoS článku

001365219400001

EID výsledku v databázi Scopus

2-s2.0-85210516828