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

Karin Thorsheim Daniel Willén Emil Tykesson Jonas Ståhle Jean-Pierre Praly 1 Sébastien Vidal 1 Magnus Johnson Göran Widmalm 2 Sophie Manner Ulf Ellervik
1 CO2GLYCO - Chimie Organique 2-Glycochimie
ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
2 Stockholm University
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.
Keywords : carbohydrates enzymes structure-activity relationships xylosides
Document type :
Journal articles
Complete list of metadatas
https://hal-udl.archives-ouvertes.fr/hal-02121732
Contributor : Umr5246 Icbms <>
Submitted on : Monday, May 6, 2019 - 5:19:08 PM
Last modification on : Wednesday, May 22, 2019 - 4:24:07 PM

Links full text

openaccess

Identifiers

Collections

UNIV-LYON1 | INC-CNRS | INSA-LYON | INSA-GROUPE

Citation

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, Wiley-VCH Verlag, 2017, 23 (71), pp.18057-18065. ⟨10.1002/chem.201704267⟩. ⟨hal-02121732⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

16

Contact

CCSD