Polymeric iminosugars improve the activity of carbohydrate-processing enzymes.
Multivalent iminosugars have recently emerged as powerful tools to inhibit the activities of specific glycosidases. In this work, biocompatible dextrans were coated with iminosugars to form linear and ramified polymers with unprecedently high valencies (from 20 to 900) to probe the evolution of the multivalent inhibition as a function of ligand valency. This study led to the discovery that polyvalent iminosugars can also significantly enhance, not only inhibit, the enzymatic activity of specific glycoside-hydrolase, as observed on two galactosidases, a fucosidase, and a bacterial mannoside phosphorylase for which an impressive 70-fold activation was even reached. The concept of glycosidase activation is largely unexplored, with a unique recent example of small-molecules activators of a bacterial O-GlcNAc hydrolase. The possibility of using these polymers as "artificial enzyme effectors" may therefore open up new perspectives in therapeutics and biocatalysis.
†LUNAM Université, CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
Yoan
Y
Brissonnet
‡Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, Institut National des Sciences Appliquées, CNRS UMR5504, Institut National de Recherche Agronomique, UMR792, 135 Ave. de Rangueil, 31077 Toulouse, France.
Simon
S
Ladevèze
†LUNAM Université, CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
David
D
Tezé
§Université Lille 1, Unité de Glycobiologie Structurale et Fonctionnelle, UMR 8576, 59650 Villeneuve d'Ascq, France.
Emeline
E
Fabre
†LUNAM Université, CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
David
D
Deniaud
⊥UFIP, UMR CNRS 6286, Faculté des Sciences et Techniques, Université de Nantes, 2 rue de la Houssinière, F-44322 Nantes, France.
Franck
F
Daligault
⊥UFIP, UMR CNRS 6286, Faculté des Sciences et Techniques, Université de Nantes, 2 rue de la Houssinière, F-44322 Nantes, France.
Charles
C
Tellier
∥Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravska cesta 9, 845 38 Bratislava, Slovakia.
Sergej
S
Šesták
‡Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, Institut National des Sciences Appliquées, CNRS UMR5504, Institut National de Recherche Agronomique, UMR792, 135 Ave. de Rangueil, 31077 Toulouse, France.
Magali
M
Remaud-Simeon
‡Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, Institut National des Sciences Appliquées, CNRS UMR5504, Institut National de Recherche Agronomique, UMR792, 135 Ave. de Rangueil, 31077 Toulouse, France.
Gabrielle
G
Potocki-Veronese
†LUNAM Université, CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
Sébastien G
SG
Gouin
D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D004789:Enzyme Activation; D006026:Glycoside Hydrolases / Q000737:chemistry*; D050111:Imino Sugars / Q000737:chemistry*; D008024:Ligands; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry; D006005:Phosphorylases / Q000737:chemistry; D058105:Polymerization; D005644:alpha-L-Fucosidase / Q000737:chemistry
D020099:Coated Materials, Biocompatible; D003911:Dextrans; D050111:Imino Sugars; D008024:Ligands; D006005:Phosphorylases; D010727:Phosphoric Diester Hydrolases; D006026:Glycoside Hydrolases; D005644:alpha-L-Fucosidase