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Synthesis, conformation and biology of naphthoxylosides.

Siegbahn, Anna; Aili, Ulrika LU ; Ochocinska, Agata; Olofsson, Martin; Rönnols, Jerk; Mani, Katrin LU ; Widmalm, Göran and Ellervik, Ulf (2011) In Bioorganic & Medicinal Chemistry 19. p.4114-4126
Abstract
Proteoglycans (PG) are polyanionic proteins consisting of a core protein substituted with carbohydrate chains, that is, glycosaminoglycans (GAG). The biosynthesis of GAG can be manipulated by simple xylosides carrying hydrophobic aglycons, which can enter the cell and initiate the biosynthesis. While the importance of the aglycon is well investigated, there is far less information on the effect of modifications in the xylose residue. We have developed a new synthetic protocol, based on acetal protection and selective benzylation, for modification of the three hydroxyl groups in xylose. Thus we have synthesized twelve analogs of 2-naphthyl β-d-xylopyranoside (XylNap), where each hydroxyl group has been epimerized or replaced by methoxy,... (More)
Proteoglycans (PG) are polyanionic proteins consisting of a core protein substituted with carbohydrate chains, that is, glycosaminoglycans (GAG). The biosynthesis of GAG can be manipulated by simple xylosides carrying hydrophobic aglycons, which can enter the cell and initiate the biosynthesis. While the importance of the aglycon is well investigated, there is far less information on the effect of modifications in the xylose residue. We have developed a new synthetic protocol, based on acetal protection and selective benzylation, for modification of the three hydroxyl groups in xylose. Thus we have synthesized twelve analogs of 2-naphthyl β-d-xylopyranoside (XylNap), where each hydroxyl group has been epimerized or replaced by methoxy, fluoro, or hydrogen. To gain more information about the properties of xylose, conformational studies were made on some of the analogs. It was found that the (4)C(1) conformation is highly predominant, accompanied by a nonnegligible population of the (2)S(0) conformation. However, deoxygenation at C3 results in a large portion of the (1)C(4) conformation. The GAG priming ability and proliferation activity of the twelve analogs, were investigated using a matched pair of human breast fibroblasts and human breast carcinoma cells. None of the analogs initiated the biosynthesis of GAG, but an inhibitory effect on endogenous PG production was observed for analogs fluorinated or deoxygenated at C4. From our data it seems reasonable that all three hydroxyl groups in XylNap are essential for the priming of GAG chains and for selective toxicity for tumor cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Bioorganic & Medicinal Chemistry
volume
19
pages
4114 - 4126
publisher
Elsevier
external identifiers
  • wos:000291934700027
  • pmid:21622002
  • scopus:79959497980
ISSN
0968-0896
DOI
10.1016/j.bmc.2011.05.007
language
English
LU publication?
yes
id
7ac329b6-0bcc-44d7-ba69-83bb40b507b6 (old id 1971933)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21622002?dopt=Abstract
date added to LUP
2011-06-07 23:40:45
date last changed
2017-09-24 04:40:26
@article{7ac329b6-0bcc-44d7-ba69-83bb40b507b6,
  abstract     = {Proteoglycans (PG) are polyanionic proteins consisting of a core protein substituted with carbohydrate chains, that is, glycosaminoglycans (GAG). The biosynthesis of GAG can be manipulated by simple xylosides carrying hydrophobic aglycons, which can enter the cell and initiate the biosynthesis. While the importance of the aglycon is well investigated, there is far less information on the effect of modifications in the xylose residue. We have developed a new synthetic protocol, based on acetal protection and selective benzylation, for modification of the three hydroxyl groups in xylose. Thus we have synthesized twelve analogs of 2-naphthyl β-d-xylopyranoside (XylNap), where each hydroxyl group has been epimerized or replaced by methoxy, fluoro, or hydrogen. To gain more information about the properties of xylose, conformational studies were made on some of the analogs. It was found that the (4)C(1) conformation is highly predominant, accompanied by a nonnegligible population of the (2)S(0) conformation. However, deoxygenation at C3 results in a large portion of the (1)C(4) conformation. The GAG priming ability and proliferation activity of the twelve analogs, were investigated using a matched pair of human breast fibroblasts and human breast carcinoma cells. None of the analogs initiated the biosynthesis of GAG, but an inhibitory effect on endogenous PG production was observed for analogs fluorinated or deoxygenated at C4. From our data it seems reasonable that all three hydroxyl groups in XylNap are essential for the priming of GAG chains and for selective toxicity for tumor cells.},
  author       = {Siegbahn, Anna and Aili, Ulrika and Ochocinska, Agata and Olofsson, Martin and Rönnols, Jerk and Mani, Katrin and Widmalm, Göran and Ellervik, Ulf},
  issn         = {0968-0896},
  language     = {eng},
  pages        = {4114--4126},
  publisher    = {Elsevier},
  series       = {Bioorganic & Medicinal Chemistry},
  title        = {Synthesis, conformation and biology of naphthoxylosides.},
  url          = {http://dx.doi.org/10.1016/j.bmc.2011.05.007},
  volume       = {19},
  year         = {2011},
}