Naphthyl Thio- and Carba-xylopyranosides for Exploration of the Active Site of [beta]-1,4-Galactosyltransferase 7 ([beta]4GalT7)
Xyloside analogues with substitution of the endocyclic oxygen atom by sulfur or carbon were investigated as substrates for [beta]-1,4-galactosyltransferase7 ([beta]4GalT7), a key enzyme in the biosynthesis of glycosaminoglycan chains. The analogues with an endocyclic sulfur atom proved to be excelle...
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| Veröffentlicht in: | Chemistry : a European journal 2017-12, Vol.23 (71), p.18057 |
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| container_issue | 71 |
| container_start_page | 18057 |
| container_title | Chemistry : a European journal |
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| creator | Thorsheim, Karin Willen, Daniel Tykesson, Emil Stahle, Jonas Praly, Jean-Pierre Vidal, Sébastien Johnson, Magnus T Widmalm, Göran Manner, Sophie Ellervik, Ulf |
| description | Xyloside analogues with substitution of the endocyclic oxygen atom by sulfur or carbon were investigated as substrates for [beta]-1,4-galactosyltransferase7 ([beta]4GalT7), a key enzyme in the biosynthesis of glycosaminoglycan chains. The analogues with an endocyclic sulfur atom proved to be excellent substrates for [beta]4GalT7, and were galactosylated approximately fifteen times more efficiently than the corresponding xyloside. The 5a-carba-[beta]-xylopyranoside in the d-configuration proved to be a good substrate for [beta]4GalT7, 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. |
| doi_str_mv | 10.1002/chem.201704267 |
| format | Article |
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The analogues with an endocyclic sulfur atom proved to be excellent substrates for [beta]4GalT7, and were galactosylated approximately fifteen times more efficiently than the corresponding xyloside. The 5a-carba-[beta]-xylopyranoside in the d-configuration proved to be a good substrate for [beta]4GalT7, 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.</description><identifier>ISSN: 0947-6539</identifier><identifier>EISSN: 1521-3765</identifier><identifier>DOI: 10.1002/chem.201704267</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>Biosynthesis ; Chains ; Chemistry ; Configurations ; Crystal structure ; Crystallography ; Enzymes ; Magnetic resonance spectroscopy ; Molecular modelling ; NMR ; NMR spectroscopy ; Nuclear magnetic resonance ; Primers ; Substrates ; Sulfur ; Tyrosine ; X-ray crystallography ; Xylopyranoside</subject><ispartof>Chemistry : a European journal, 2017-12, Vol.23 (71), p.18057</ispartof><rights>2017 Wiley-VCH Verlag GmbH & Co. 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| ispartof | Chemistry : a European journal, 2017-12, Vol.23 (71), p.18057 |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Biosynthesis Chains Chemistry Configurations Crystal structure Crystallography Enzymes Magnetic resonance spectroscopy Molecular modelling NMR NMR spectroscopy Nuclear magnetic resonance Primers Substrates Sulfur Tyrosine X-ray crystallography Xylopyranoside |
| title | Naphthyl Thio- and Carba-xylopyranosides for Exploration of the Active Site of [beta]-1,4-Galactosyltransferase 7 ([beta]4GalT7) |
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