Synthesis of Double-Modified Xyloside Analogues for Probing the β4GalT7 Active Site
Willén, Daniel LU ; Bengtsson, Dennis ; Clementson, Sebastian ; Tykesson, Emil LU
; Manner, Sophie
LU
and Ellervik, Ulf
LU
(2018)
In Journal of Organic Chemistry
83(3).
p.1259-1277
- Abstract
Monosubstituted naphthoxylosides have been shown to function as substrates for, and inhibitors of, the enzyme β4GalT7, a key enzyme in the biosynthetic pathway leading to glycosaminoglycans and proteoglycans. In this article, we explore the synthesis of 16 xyloside analogues, modified at two different positions, as well as their function as inhibitors of and/or substrates for the enzyme. Seemingly simple compounds turned out to require complex synthetic pathways. A meta-analysis of the synthetic work shows that, regardless of the abundance of methods available for carbohydrate synthesis, even simple modifications can turn out to be problematic, and double modifications present additional challenges due to conformational, steric, and... (More)
Monosubstituted naphthoxylosides have been shown to function as substrates for, and inhibitors of, the enzyme β4GalT7, a key enzyme in the biosynthetic pathway leading to glycosaminoglycans and proteoglycans. In this article, we explore the synthesis of 16 xyloside analogues, modified at two different positions, as well as their function as inhibitors of and/or substrates for the enzyme. Seemingly simple compounds turned out to require complex synthetic pathways. A meta-analysis of the synthetic work shows that, regardless of the abundance of methods available for carbohydrate synthesis, even simple modifications can turn out to be problematic, and double modifications present additional challenges due to conformational, steric, and stereoelectronic effects.
(Less)
- author
- Willén, Daniel
LU
; Bengtsson, Dennis
; Clementson, Sebastian
; Tykesson, Emil
LU
; Manner, Sophie
LU
and Ellervik, Ulf
LU
- organization
- publishing date
- 2018-02-02
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Organic Chemistry
- volume
- 83
- issue
- 3
- pages
- 19 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:29282986
- scopus:85041624906
- ISSN
- 0022-3263
- DOI
- 10.1021/acs.joc.7b02809
- language
- English
- LU publication?
- yes
- id
- 5c2bd194-d347-4ec8-a1e8-65dc59e60feb
- date added to LUP
- 2018-02-21 10:07:50
- date last changed
- 2024-06-24 10:08:41
@article{5c2bd194-d347-4ec8-a1e8-65dc59e60feb,
abstract = {{<p>Monosubstituted naphthoxylosides have been shown to function as substrates for, and inhibitors of, the enzyme β4GalT7, a key enzyme in the biosynthetic pathway leading to glycosaminoglycans and proteoglycans. In this article, we explore the synthesis of 16 xyloside analogues, modified at two different positions, as well as their function as inhibitors of and/or substrates for the enzyme. Seemingly simple compounds turned out to require complex synthetic pathways. A meta-analysis of the synthetic work shows that, regardless of the abundance of methods available for carbohydrate synthesis, even simple modifications can turn out to be problematic, and double modifications present additional challenges due to conformational, steric, and stereoelectronic effects.</p>}},
author = {{Willén, Daniel and Bengtsson, Dennis and Clementson, Sebastian and Tykesson, Emil and Manner, Sophie and Ellervik, Ulf}},
issn = {{0022-3263}},
language = {{eng}},
month = {{02}},
number = {{3}},
pages = {{1259--1277}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Journal of Organic Chemistry}},
title = {{Synthesis of Double-Modified Xyloside Analogues for Probing the β4GalT7 Active Site}},
url = {{http://dx.doi.org/10.1021/acs.joc.7b02809}},
doi = {{10.1021/acs.joc.7b02809}},
volume = {{83}},
year = {{2018}},
}