The multivalent effect in glycosidase inhibition: probing the influence of architectural parameters with cyclodextrin-based iminosugar click clusters.
Chemistry
; 17(49): 13825-31, 2011 Dec 02.
Article
in En
| MEDLINE
| ID: mdl-22052823
ABSTRACT
In contrast to most lectins, glycosidases may appear to be unpromising targets for multivalent binding because they display only a single active site. To explore the potential of multivalency on glycosidase inhibition, unprecedented cyclodextrin-based iminosugar conjugates have been designed and prepared. The synthesis was performed by way of Cu(I) -catalyzed azide-alkyne cycloaddition reaction under microwave activation between propargylated multivalent ß-cyclodextrins and an azide-armed N-alkyl 1-deoxynojirimycin derivative. Evaluation with a panel of glycosidases of this new class of glycomimetic clusters revealed the strongest affinity enhancement observed to date for a multivalent glycosidase inhibitor, with binding enhancement up to four orders of magnitude over the corresponding monovalent ligand for α-mannosidase. These results demonstrate that the multivalency concept extends beyond carbohydrate-lectin recognition processes to glycomimetic-enzyme inhibition.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Beta-Cyclodextrins
/
Imino Sugars
/
Glycoside Hydrolases
Language:
En
Journal:
Chemistry
Journal subject:
QUIMICA
Year:
2011
Document type:
Article
Affiliation country:
France