Sophie Manner
Studierektor
Naphthyl Thio- and Carba-xylopyranosides for Exploration of the Active Site of β-1,4-Galactosyltransferase 7 (β4GalT7)
Författare
Summary, in English
Xyloside analogues with substitution of the endocyclic oxygen atom by sulfur or carbon were investigated as substrates for β-1,4-galactosyltransferase 7 (β4GalT7), a key enzyme in the biosynthesis of glycosaminoglycan chains. The analogues with an endocyclic sulfur atom proved to be excellent substrates for β4GalT7, and were galactosylated approximately fifteen times more efficiently than the corresponding xyloside. The 5a-carba-β-xylopyranoside in the d-configuration proved to be a good substrate for β4GalT7, whereas the enantiomer in the l-configuration showed no activity. Further investigations by X-ray crystallography, NMR spectroscopy, and molecular modeling provided a rationale for the pronounced activity of the sulfur analogues. Favorable π–π interactions between the 2-naphthyl moiety and a tyrosine side chain of the enzyme were observed for the thio analogues, which open up for the design of efficient GAG primers and inhibitors.
Avdelning/ar
- Centrum för analys och syntes
- Matrix Biology
Publiceringsår
2017-12-19
Språk
Engelska
Sidor
18057-18065
Publikation/Tidskrift/Serie
Chemistry - A European Journal
Volym
23
Issue
71
Dokumenttyp
Artikel i tidskrift
Förlag
Wiley-Blackwell
Ämne
- Organic Chemistry
Nyckelord
- carbohydrates
- enzymes
- structure–activity relationships
- xylosides
Status
Published
Forskningsgrupp
- Matrix Biology
ISBN/ISSN/Övrigt
- ISSN: 0947-6539