Naphthyl Thio- and Carba-xylopyranosides for Exploration of the Active Site of β-1,4-Galactosyltransferase 7 (β4GalT7) - Archive ouverte HAL Access content directly
Journal Articles Chemistry - A European Journal Year : 2017

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

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Karin Thorsheim
  • Function : Author
Daniel Willén
  • Function : Author
Emil Tykesson
  • Function : Author
Jonas Ståhle
  • Function : Author
Magnus Johnson
  • Function : Author
Göran Widmalm
Sophie Manner
  • Function : Author
Ulf Ellervik
  • Function : Author

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.

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hal-02121732 , version 1 (06-05-2019)

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Karin Thorsheim, Daniel Willén, Emil Tykesson, Jonas Ståhle, Jean-Pierre Praly, et al.. Naphthyl Thio- and Carba-xylopyranosides for Exploration of the Active Site of β-1,4-Galactosyltransferase 7 (β4GalT7). Chemistry - A European Journal, 2017, 23 (71), pp.18057-18065. ⟨10.1002/chem.201704267⟩. ⟨hal-02121732⟩
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