Synthesis of a library of variously modified 4-methylumbelliferyl xylosides and a structure-activity study of human β4GalT7.
Fiche publication
Date publication
novembre 2017
Journal
Organic & biomolecular chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FOURNEL-GIGLEUX Sylvie, Dr GULBERTI Sandrine
Tous les auteurs :
Dahbi S, Jacquinet JC, Bertin-Jung I, Robert A, Ramalanjaona N, Gulberti S, Fournel-Gigleux S, Lopin-Bon C
Lien Pubmed
Résumé
Proteoglycans (PGs) are complex macromolecules that are composed of glycosaminoglycan (GAG) chains covalently attached to a core protein through a tetrasaccharide linker. The biosynthesis of PGs is complex and involves a large number of glycosyltranferases. Here we present a structure-activity study of human β4GalT7, which transfers the first Gal residue onto a xyloside moiety of the linkage region. An efficient and regiocontrolled synthesis of a library of modified analogs of 4-methylumbelliferyl xyloside (XylMU) is reported herein. Hydroxyl groups at the position C-2, C-3 or C-4 have been epimerized and/or replaced by a hydrogen or a fluorine, while the anomeric oxygen was replaced by either a sulfur or a sulfone. The effect of these compounds on human β4GalT7 activity in vitro and on GAG biosynthesis in cellulo was then evaluated.
Mots clés
Carbohydrate Conformation, Galactosyltransferases, metabolism, Glycosides, biosynthesis, Humans, Small Molecule Libraries, chemistry, Structure-Activity Relationship
Référence
Org. Biomol. Chem.. 2017 Nov 22;15(45):9653-9669