Title :

Multivalent Thiosialosides and Their Synergistic Interaction with Pathogenic Sialidases

Author(s) :

Brissonnet, Yoan [Auteur]
Assailly, Coralie [Auteur]
Saumonneau, Amélie [Auteur]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Maillasson, Mike [Auteur]
Petitot, Clémence [Auteur]
Roubinet, Benoit [Auteur]
Didak, Blanka [Auteur]
Landemarre, Ludovic [Auteur]
Bridot, Clarisse [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Blossey, Ralf [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Deniaud, David [Auteur]
Yan, Xibo [Auteur]
Bernard, Julien [Auteur]
Tellier, Charles [Auteur]
Grandjean, Cyrille [Auteur]
Daligault, Franck [Auteur]
Gouin, Sébastien G. [Auteur]

Journal title :

Chemistry - A European Journal

Abbreviated title :

Chem. Eur. J.

Volume number :

25

Pages :

2358-2365

Publisher :

Wiley

Publication date :

2019-01-11

ISSN :

0947-6539

English keyword(s) :

enzymes
glycoclusters
glycosidases
inhibition
sialidases

HAL domain(s) :

Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique

English abstract : [en]

Sialidases (SAs) hydrolyze sialyl residues from glycoconjugates of the eukaryotic cell surface and are virulence factors expressed by pathogenic bacteria, viruses, and parasites. The catalytic domains of SAs are often ...
Show more >Sialidases (SAs) hydrolyze sialyl residues from glycoconjugates of the eukaryotic cell surface and are virulence factors expressed by pathogenic bacteria, viruses, and parasites. The catalytic domains of SAs are often flanked with carbohydrate‐binding module(s) previously shown to bind sialosides and to enhance enzymatic catalytic efficiency. Herein, non‐hydrolyzable multivalent thiosialosides were designed as probes and inhibitors of V. cholerae, T. cruzi, and S. pneumoniae (NanA) sialidases. NanA was truncated from the catalytic and lectinic domains (NanA‐L and NanA‐C) to probe their respective roles upon interacting with sialylated surfaces and the synthetically designed di‐ and polymeric thiosialosides. The NanA‐L domain was shown to fully drive NanA binding, improving affinity for the thiosialylated surface and compounds by more than two orders of magnitude. Importantly, each thiosialoside grafted onto the polymer was also shown to reduce NanA and NanA‐C catalytic activity with efficiency that was 3000‐fold higher than that of the monovalent thiosialoside reference. These results extend the concept of multivalency for designing potent bacterial and parasitic sialidase inhibitors.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Computational Molecular Systems Biology

Submission date :

2021-01-04T09:00:52Z
2021-01-07T12:07:09Z