Title :

α-L-fucosidase inhibition by pyrrolidine-ferrocene hybrids: rationalization of ligand-binding properties by structural studies

Author(s) :

Hottin, Audrey [Auteur]
Institut de Chimie Moléculaire de Reims - UMR 7312 [ICMR]
Wright, Daniel W. [Auteur]
University of York [York, UK]
Steenackers, Agata [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Delannoy, Philippe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Dubar, Faustine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Biot, Christophe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Davies, Gideon J. [Auteur]
University of York [York, UK]
Behr, Jean-Bernard [Auteur]
Institut de Chimie Moléculaire de Reims - UMR 7312 [ICMR]

Journal title :

Chemistry (Weinheim an der Bergstrasse, Germany)

Abbreviated title :

Chemistry

Volume number :

19

Pages :

9526-9533

Publication date :

2013-07-15

ISSN :

1521-3765

HAL domain(s) :

Chimie/Chimie théorique et/ou physique
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie moléculaire

English abstract : [en]

Enhanced metabolism of fucose through fucosidase overexpression is a signature of some cancer types, thus suggesting that fucosidase-targetted ligands could play the role of drug-delivery vectors. Herein, we describe the ...
Show more >Enhanced metabolism of fucose through fucosidase overexpression is a signature of some cancer types, thus suggesting that fucosidase-targetted ligands could play the role of drug-delivery vectors. Herein, we describe the synthesis of a new series of pyrrolidine-ferrocene conjugates, consisting of a L-fuco-configured dihydroxypyrrolidine as the fucosidase ligand armed with a cytotoxic ferrocenylamine moeity. Three-dimensional structures of several of these fucosidase inhibitors reveal transition-state-mimicking (3)E conformations. Elaboration with the ferrocenyl moiety results in sub-micromolar inhibitors of both bovine and bacterial fucosidases, with the 3D structure of the latter revealing electron density indicative of highly mobile alkylferrocene compounds. The best compounds show a strong antiproliferative effect, with up to 100% inhibition of the proliferation of MDA-MB-231 cancer cells at 50 μM.Show less >

Language :

Anglais

Audience :

Non spécifiée

Administrative institution(s) :

CNRS
Université de Lille

Collections :

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

Research team(s) :

Régulation de la glycosylation terminale
Chemical Glycobiology

Submission date :

2020-02-12T15:11:08Z
2021-03-03T08:38:45Z