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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1971933
- author
- Siegbahn, Anna
; Aili, Ulrika
LU
; Ochocinska, Agata
; Olofsson, Martin
; Rönnols, Jerk
; Mani, Katrin
LU
; Widmalm, Göran
and Ellervik, Ulf
- organization
- publishing date
- 2011
- 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
- pmid:21622002
- 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
- 2016-04-04 08:56:45
- date last changed
- 2023-09-05 18:33:17
@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}},
doi = {{10.1016/j.bmc.2011.05.007}},
volume = {{19}},
year = {{2011}},
}