Naphthyl Thio- and Carba-xylopyranosides for Exploration of the Active Site of β-1,4-Galactosyltransferase 7 (β4GalT7)
(2017) In Chemistry - A European Journal 23(71). p.18057-18065- 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.... (More)
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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- author
- Thorsheim, Karin LU ; Willén, Daniel LU ; Tykesson, Emil LU ; Ståhle, Jonas ; Praly, Jean Pierre ; Vidal, Sébastien ; Johnson, Magnus T. LU ; Widmalm, Göran ; Manner, Sophie LU and Ellervik, Ulf LU
- organization
- publishing date
- 2017-12-19
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- carbohydrates, enzymes, structure–activity relationships, xylosides
- in
- Chemistry - A European Journal
- volume
- 23
- issue
- 71
- pages
- 9 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:29024190
- wos:000418356700030
- scopus:85035223936
- ISSN
- 0947-6539
- DOI
- 10.1002/chem.201704267
- language
- English
- LU publication?
- yes
- id
- 50e95737-9077-4511-aedc-78824232ae51
- date added to LUP
- 2018-01-05 08:13:12
- date last changed
- 2024-09-16 13:49:07
@article{50e95737-9077-4511-aedc-78824232ae51, abstract = {{<p>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.</p>}}, author = {{Thorsheim, Karin and Willén, Daniel and Tykesson, Emil and Ståhle, Jonas and Praly, Jean Pierre and Vidal, Sébastien and Johnson, Magnus T. and Widmalm, Göran and Manner, Sophie and Ellervik, Ulf}}, issn = {{0947-6539}}, keywords = {{carbohydrates; enzymes; structure–activity relationships; xylosides}}, language = {{eng}}, month = {{12}}, number = {{71}}, pages = {{18057--18065}}, publisher = {{Wiley-Blackwell}}, series = {{Chemistry - A European Journal}}, title = {{Naphthyl Thio- and Carba-xylopyranosides for Exploration of the Active Site of β-1,4-Galactosyltransferase 7 (β4GalT7)}}, url = {{http://dx.doi.org/10.1002/chem.201704267}}, doi = {{10.1002/chem.201704267}}, volume = {{23}}, year = {{2017}}, }