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Hydroxylated oxanes as xyloside analogs for determination of the minimal binding requirements of β4GalT7

Thorsheim, Karin LU ; Clementson, Sebastian; Tykesson, Emil LU ; Strand, Daniel LU ; Ellervik, Ulf LU and Bengtsson, Dennis (2017) In Tetrahedron Letters 58(35). p.3466-3469
Abstract

β-1,4-Galactosyltransferase 7 (β4GalT7) is a key enzyme in the biosynthesis of glycosaminoglycan (GAG) chains. Natural and synthetic xylosides can be used to both inhibit and prime GAG synthesis by acting as inhibitors or substrates for β4GalT7. In this report, we exploit hydroxylated oxanes as deoxygenated xyloside analogs to clarify the minimum protein-ligand interactions required for galactosylation and/or inhibition. Enantiomerically pure substances were synthesized using a chiral pool approach whereas the corresponding racemates were obtained from simple starting materials. The results of a β4GalT7 assay show that a single hydroxyl group on an oxane ring is insufficient to induce galactosylation or inhibition, which implies that at... (More)

β-1,4-Galactosyltransferase 7 (β4GalT7) is a key enzyme in the biosynthesis of glycosaminoglycan (GAG) chains. Natural and synthetic xylosides can be used to both inhibit and prime GAG synthesis by acting as inhibitors or substrates for β4GalT7. In this report, we exploit hydroxylated oxanes as deoxygenated xyloside analogs to clarify the minimum protein-ligand interactions required for galactosylation and/or inhibition. Enantiomerically pure substances were synthesized using a chiral pool approach whereas the corresponding racemates were obtained from simple starting materials. The results of a β4GalT7 assay show that a single hydroxyl group on an oxane ring is insufficient to induce galactosylation or inhibition, which implies that at least two substituents, one of which being 3-OH, needs to be present.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chiral pool approach, De novo synthesis, Mechanistic probes, Xyloside analogs, β4GalT7
in
Tetrahedron Letters
volume
58
issue
35
pages
4 pages
publisher
Elsevier
external identifiers
  • scopus:85026414813
ISSN
0040-4039
DOI
10.1016/j.tetlet.2017.07.078
language
English
LU publication?
yes
id
db7ce79e-fc0a-46f9-8df3-dc4eebf26eb3
date added to LUP
2017-08-29 12:47:35
date last changed
2018-02-18 05:03:14
@article{db7ce79e-fc0a-46f9-8df3-dc4eebf26eb3,
  abstract     = {<p>β-1,4-Galactosyltransferase 7 (β4GalT7) is a key enzyme in the biosynthesis of glycosaminoglycan (GAG) chains. Natural and synthetic xylosides can be used to both inhibit and prime GAG synthesis by acting as inhibitors or substrates for β4GalT7. In this report, we exploit hydroxylated oxanes as deoxygenated xyloside analogs to clarify the minimum protein-ligand interactions required for galactosylation and/or inhibition. Enantiomerically pure substances were synthesized using a chiral pool approach whereas the corresponding racemates were obtained from simple starting materials. The results of a β4GalT7 assay show that a single hydroxyl group on an oxane ring is insufficient to induce galactosylation or inhibition, which implies that at least two substituents, one of which being 3-OH, needs to be present.</p>},
  author       = {Thorsheim, Karin and Clementson, Sebastian and Tykesson, Emil and Strand, Daniel and Ellervik, Ulf and Bengtsson, Dennis},
  issn         = {0040-4039},
  keyword      = {Chiral pool approach,De novo synthesis,Mechanistic probes,Xyloside analogs,β4GalT7},
  language     = {eng},
  month        = {08},
  number       = {35},
  pages        = {3466--3469},
  publisher    = {Elsevier},
  series       = {Tetrahedron Letters},
  title        = {Hydroxylated oxanes as xyloside analogs for determination of the minimal binding requirements of β4GalT7},
  url          = {http://dx.doi.org/10.1016/j.tetlet.2017.07.078},
  volume       = {58},
  year         = {2017},
}