Iminosugar-Cyclopeptoid Conjugates Raise Multivalent Effect in Glycosidase Inhibition at Unprecedented High Levels.
Fiche publication
Date publication
avril 2016
Journal
Chemistry (Weinheim an der Bergstrasse, Germany)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BIRCK Catherine
Tous les auteurs :
Lepage ML, Schneider JP, Bodlenner A, Meli A, De Riccardis F, Schmitt M, Tarnus C, Nguyen-Huynh NT, Francois YN, Leize-Wagner E, Birck C, Cousido-Siah A, Podjarny A, Izzo I, Compain P
Lien Pubmed
Résumé
A series of cyclopeptoid-based iminosugar clusters has been evaluated to finely probe the ligand content-dependent increase in α-mannosidase inhibition. This study led to the largest binding enhancement ever reported for an enzyme inhibitor (up to 4700-fold on a valency-corrected basis), which represents a substantial advance over the multivalent glycosidase inhibitors previously reported. Electron microscopy imaging and analytical data support, for the best multivalent effects, the formation of a strong chelate complex in which two mannosidase molecules are cross-linked by one inhibitor.
Mots clés
Enzyme Inhibitors, chemistry, Glycoside Hydrolases, antagonists & inhibitors, Imino Sugars, chemistry, Ligands, Peptides, Cyclic, chemistry, alpha-Mannosidase, chemistry
Référence
Chemistry. 2016 Apr;22(15):5151-5