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Disubstituted naphthyl β-D-xylopyranosides : Synthesis, GAG priming, and histone acetyltransferase (HAT) inhibition

Thorsheim, Karin LU ; Persson, Andrea LU ; Siegbahn, Anna LU ; Tykesson, Emil LU orcid ; Westergren-Thorsson, Gunilla LU orcid ; Mani, Katrin LU orcid and Ellervik, Ulf LU orcid (2016) In Glycoconjugate Journal 33(2). p.57-245
Abstract

Xylosides are a group of compounds that can induce glycosaminoglycan (GAG) chain synthesis independently of a proteoglycan core protein. We have previously shown that the xyloside 2-(6-hydroxynaphthyl)β-D-xylopyranoside has a tumor-selective growth inhibitory effect both in vitro and in vivo, and that the effect in vitro was correlated to a reduction in histone H3 acetylation. In addition, GAG chains have previously been reported to inhibit histone acetyltransferases (HAT). To investigate if xylosides, or the corresponding xyloside-primed GAG chains, can be used as HAT inhibitors, we have synthesized a series of naphthoxylosides carrying structural motifs similar to the aromatic moieties of the known HAT inhibitors garcinol and... (More)

Xylosides are a group of compounds that can induce glycosaminoglycan (GAG) chain synthesis independently of a proteoglycan core protein. We have previously shown that the xyloside 2-(6-hydroxynaphthyl)β-D-xylopyranoside has a tumor-selective growth inhibitory effect both in vitro and in vivo, and that the effect in vitro was correlated to a reduction in histone H3 acetylation. In addition, GAG chains have previously been reported to inhibit histone acetyltransferases (HAT). To investigate if xylosides, or the corresponding xyloside-primed GAG chains, can be used as HAT inhibitors, we have synthesized a series of naphthoxylosides carrying structural motifs similar to the aromatic moieties of the known HAT inhibitors garcinol and curcumin, and studied their biological activities. Here, we show that the disubstituted naphthoxylosides induced GAG chain synthesis, and that the ones with at least one free phenolic group exhibited moderate HAT inhibition in vitro, without affecting histone H3 acetylation in cell culture. The xyloside-primed GAG chains, on the other hand, had no effect on HAT activity, possibly explaining why the effect of the xylosides on histone H3 acetylation was absent in cell culture as the xylosides were recruited for GAG chain synthesis. Further investigations are required to find xylosides that are effective HAT inhibitors or xylosides producing GAG chains with HAT inhibitory effects.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Glycoconjugate Journal
volume
33
issue
2
pages
13 pages
publisher
Springer
external identifiers
  • pmid:27023911
  • scopus:84962288787
  • wos:000374677600014
ISSN
1573-4986
DOI
10.1007/s10719-016-9662-6
language
English
LU publication?
yes
id
15d64c58-22d2-4bd4-abae-2503a3db0d96
date added to LUP
2016-04-18 12:09:22
date last changed
2025-01-12 00:53:34
@article{15d64c58-22d2-4bd4-abae-2503a3db0d96,
  abstract     = {{<p>Xylosides are a group of compounds that can induce glycosaminoglycan (GAG) chain synthesis independently of a proteoglycan core protein. We have previously shown that the xyloside 2-(6-hydroxynaphthyl)β-D-xylopyranoside has a tumor-selective growth inhibitory effect both in vitro and in vivo, and that the effect in vitro was correlated to a reduction in histone H3 acetylation. In addition, GAG chains have previously been reported to inhibit histone acetyltransferases (HAT). To investigate if xylosides, or the corresponding xyloside-primed GAG chains, can be used as HAT inhibitors, we have synthesized a series of naphthoxylosides carrying structural motifs similar to the aromatic moieties of the known HAT inhibitors garcinol and curcumin, and studied their biological activities. Here, we show that the disubstituted naphthoxylosides induced GAG chain synthesis, and that the ones with at least one free phenolic group exhibited moderate HAT inhibition in vitro, without affecting histone H3 acetylation in cell culture. The xyloside-primed GAG chains, on the other hand, had no effect on HAT activity, possibly explaining why the effect of the xylosides on histone H3 acetylation was absent in cell culture as the xylosides were recruited for GAG chain synthesis. Further investigations are required to find xylosides that are effective HAT inhibitors or xylosides producing GAG chains with HAT inhibitory effects.</p>}},
  author       = {{Thorsheim, Karin and Persson, Andrea and Siegbahn, Anna and Tykesson, Emil and Westergren-Thorsson, Gunilla and Mani, Katrin and Ellervik, Ulf}},
  issn         = {{1573-4986}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{57--245}},
  publisher    = {{Springer}},
  series       = {{Glycoconjugate Journal}},
  title        = {{Disubstituted naphthyl β-D-xylopyranosides : Synthesis, GAG priming, and histone acetyltransferase (HAT) inhibition}},
  url          = {{http://dx.doi.org/10.1007/s10719-016-9662-6}},
  doi          = {{10.1007/s10719-016-9662-6}},
  volume       = {{33}},
  year         = {{2016}},
}