Physiochemical Tuning of Potent Escherichia ...
Document type :
Article dans une revue scientifique
DOI :
PMID :
Permalink :
Title :
Physiochemical Tuning of Potent Escherichia coli Anti-Adhesives by Microencapsulation and Methylene Homologation
Author(s) :
Alvarez Dorta, Dimitri [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Chalopin, Thibaut [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Sivignon, Adeline [Auteur]
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH]
De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Dumych, Tetiana [Auteur]
Danylo Halytsky Lviv National Medical University [Lviv, Ukraine]
Bilyy, Rostyslav [Auteur]
Danylo Halytsky Lviv National Medical University [Lviv, Ukraine]
Deniaud, David [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Barnich, Nicolas [Auteur]
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Gouin, Sébastien G. [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Chalopin, Thibaut [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Sivignon, Adeline [Auteur]
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH]
De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Dumych, Tetiana [Auteur]
Danylo Halytsky Lviv National Medical University [Lviv, Ukraine]
Bilyy, Rostyslav [Auteur]
Danylo Halytsky Lviv National Medical University [Lviv, Ukraine]
Deniaud, David [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Barnich, Nicolas [Auteur]
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH]
Bouckaert, Julie [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Gouin, Sébastien G. [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Journal title :
ChemMedChem
Abbreviated title :
ChemMedChem
Volume number :
12
Pages :
986-998
Publication date :
2017-06-21
ISSN :
1860-7187
English keyword(s) :
Methane
Fimbriae Proteins
Adhesins, Escherichia coli
Humans
Escherichia coli
FimH antagonists
Models, Molecular
C-mannosides
Crohn Disease
Crohn's disease
anti-adhesive therapy
Bacterial Adhesion
Microbial Sensitivity Tests
Anti-Bacterial Agents
Capsules
microencapsulation
Molecular Structure
Fimbriae Proteins
Adhesins, Escherichia coli
Humans
Escherichia coli
FimH antagonists
Models, Molecular
C-mannosides
Crohn Disease
Crohn's disease
anti-adhesive therapy
Bacterial Adhesion
Microbial Sensitivity Tests
Anti-Bacterial Agents
Capsules
microencapsulation
Molecular Structure
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
Thiazolylaminomannosides (TazMan) are FimH antagonists with anti-adhesive potential against adherent-invasive Escherichia coli (AIEC) promoting gut inflammation in patients with Crohn's disease. The lead TazMan is highly ...
Show more >Thiazolylaminomannosides (TazMan) are FimH antagonists with anti-adhesive potential against adherent-invasive Escherichia coli (AIEC) promoting gut inflammation in patients with Crohn's disease. The lead TazMan is highly potent in vitro, but shows limited in vivo efficiency, probably due to low pH stability and water solubility. We recently developed a second generation of stable TazMan, but the anti-adhesive effect was lower than the first. Herein we report a co-crystal structure of the lead TazMan in FimH, revealing that the anomeric NH group and the second thiazole moiety provide a positive hydrogen bonding interaction with a trapped water molecule, and π-stacking with Tyr48 of FimH, respectively. Consequently, we developed NeoTazMan homologated with a methylene group for low-pH and mannosidase stability with a conserved NH group and bearing various heterocyclic aglycones. Microencapsulation of the lead NeoTazMan in γ-cyclodextrin dramatically improved water solubility without disrupting the affinity for FimH or the anti-adhesive effect against AIEC isolated from patients with Crohn's disease.Show less >
Show more >Thiazolylaminomannosides (TazMan) are FimH antagonists with anti-adhesive potential against adherent-invasive Escherichia coli (AIEC) promoting gut inflammation in patients with Crohn's disease. The lead TazMan is highly potent in vitro, but shows limited in vivo efficiency, probably due to low pH stability and water solubility. We recently developed a second generation of stable TazMan, but the anti-adhesive effect was lower than the first. Herein we report a co-crystal structure of the lead TazMan in FimH, revealing that the anomeric NH group and the second thiazole moiety provide a positive hydrogen bonding interaction with a trapped water molecule, and π-stacking with Tyr48 of FimH, respectively. Consequently, we developed NeoTazMan homologated with a methylene group for low-pH and mannosidase stability with a conserved NH group and bearing various heterocyclic aglycones. Microencapsulation of the lead NeoTazMan in γ-cyclodextrin dramatically improved water solubility without disrupting the affinity for FimH or the anti-adhesive effect against AIEC isolated from patients with Crohn's disease.Show less >
Language :
Anglais
Audience :
Non spécifiée
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Research team(s) :
Computational Molecular Systems Biology
Submission date :
2020-02-12T15:11:23Z
2021-05-20T07:18:01Z
2021-05-20T07:18:01Z