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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Stockholms universitet
  • Claude Bernard University Lyon 1
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Organisk kemi

Nyckelord

Originalspråkengelska
Sidor (från-till)18057-18065
Antal sidor9
TidskriftChemistry - A European Journal
Volym23
Utgåva nummer71
StatusPublished - 2017 dec 19
PublikationskategoriForskning
Peer review utfördJa