Naphthyl Thio- and Carba-xylopyranosides for Exploration of the Active Site of β-1,4-Galactosyltransferase 7 (β4GalT7)

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
Organisations
External organisations
  • Stockholm University
  • Claude Bernard University Lyon 1
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Organic Chemistry

Keywords

  • carbohydrates, enzymes, structure–activity relationships, xylosides
Original languageEnglish
Pages (from-to)18057-18065
Number of pages9
JournalChemistry - A European Journal
Volume23
Issue number71
Publication statusPublished - 2017 Dec 19
Publication categoryResearch
Peer-reviewedYes