Synthesis of a phenyl thio-b-D-galactopyranoside library from 1,5-difluoro-2,4-dinitrobenzene: discovery of efficient and selective monosaccharide inhibitors of galectin-7
(2005) In Organic and Biomolecular Chemistry 3(10). p.1922-1932- Abstract
- The galectins are a family of -galactoside-binding proteins that have been implicated in cancer and inflammation processes. Herein, we report the synthesis of a library of 28 compounds that was tested for binding to galectins-1, -3, -7, -8N and -9N. An aromatic nucleophilic substitution reaction between 1,5-difluoro-2,4-dinitrobenzene and a galacto thiol gave 5-fluoro-2,4-dinitrophenyl 2,3,4,6-tetra-O-acetyl-1-thio--D-galactopyranoside. This versatile intermediate was then modified in a two dimensional manner: either by further substitution of the second fluoride by amines or thiols, or by reduction of the nitro groups and acylation of the resulting amines, or both. Deacetylation then gave a library of aromatic -galactosides that showed... (More)
- The galectins are a family of -galactoside-binding proteins that have been implicated in cancer and inflammation processes. Herein, we report the synthesis of a library of 28 compounds that was tested for binding to galectins-1, -3, -7, -8N and -9N. An aromatic nucleophilic substitution reaction between 1,5-difluoro-2,4-dinitrobenzene and a galacto thiol gave 5-fluoro-2,4-dinitrophenyl 2,3,4,6-tetra-O-acetyl-1-thio--D-galactopyranoside. This versatile intermediate was then modified in a two dimensional manner: either by further substitution of the second fluoride by amines or thiols, or by reduction of the nitro groups and acylation of the resulting amines, or both. Deacetylation then gave a library of aromatic -galactosides that showed variable inhibitory activity against the different galectins, as shown by screening with a fluorescence-polarisation assay. Particularly efficient inhibitors were found against galectin-7, while less impressive enhancements of inhibitor affinity over methyl -D-galactopyranoside were found for galectin-1, -3, -8N and -9N. The best inhibitors against galectin-7 showed significantly higher affinity (Kd as low as 140 µM) than both -methyl galactoside (Kd 4.8 mM) and the unsubstituted -phenyl thiogalactoside (non-inhibitory). The best inhibitors against galectin-7 were poor against the other galectins and thus have potential as structurally simple and selective tools for dissecting biological functions of galectin-7. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/158687
- author
- Cumpstey, Ian LU ; Nordenfelt, Susanne LU ; Leffler, Hakon LU and Nilsson, Ulf LU
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Organic and Biomolecular Chemistry
- volume
- 3
- issue
- 10
- pages
- 1922 - 1932
- publisher
- Royal Society of Chemistry
- external identifiers
-
- wos:000229067300016
- pmid:15889175
- scopus:19944425218
- ISSN
- 1477-0539
- DOI
- 10.1039/b502354h
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240), Division of Microbiology, Immunology and Glycobiology - MIG (013025200), Paediatrics (Lund) (013002000)
- id
- 8bd1799a-8b89-443b-a6a8-64f4d66b4b84 (old id 158687)
- date added to LUP
- 2016-04-01 12:14:32
- date last changed
- 2023-02-07 11:31:06
@article{8bd1799a-8b89-443b-a6a8-64f4d66b4b84,
abstract = {{The galectins are a family of -galactoside-binding proteins that have been implicated in cancer and inflammation processes. Herein, we report the synthesis of a library of 28 compounds that was tested for binding to galectins-1, -3, -7, -8N and -9N. An aromatic nucleophilic substitution reaction between 1,5-difluoro-2,4-dinitrobenzene and a galacto thiol gave 5-fluoro-2,4-dinitrophenyl 2,3,4,6-tetra-O-acetyl-1-thio--D-galactopyranoside. This versatile intermediate was then modified in a two dimensional manner: either by further substitution of the second fluoride by amines or thiols, or by reduction of the nitro groups and acylation of the resulting amines, or both. Deacetylation then gave a library of aromatic -galactosides that showed variable inhibitory activity against the different galectins, as shown by screening with a fluorescence-polarisation assay. Particularly efficient inhibitors were found against galectin-7, while less impressive enhancements of inhibitor affinity over methyl -D-galactopyranoside were found for galectin-1, -3, -8N and -9N. The best inhibitors against galectin-7 showed significantly higher affinity (Kd as low as 140 µM) than both -methyl galactoside (Kd 4.8 mM) and the unsubstituted -phenyl thiogalactoside (non-inhibitory). The best inhibitors against galectin-7 were poor against the other galectins and thus have potential as structurally simple and selective tools for dissecting biological functions of galectin-7.}},
author = {{Cumpstey, Ian and Nordenfelt, Susanne and Leffler, Hakon and Nilsson, Ulf}},
issn = {{1477-0539}},
language = {{eng}},
number = {{10}},
pages = {{1922--1932}},
publisher = {{Royal Society of Chemistry}},
series = {{Organic and Biomolecular Chemistry}},
title = {{Synthesis of a phenyl thio-b-D-galactopyranoside library from 1,5-difluoro-2,4-dinitrobenzene: discovery of efficient and selective monosaccharide inhibitors of galectin-7}},
url = {{http://dx.doi.org/10.1039/b502354h}},
doi = {{10.1039/b502354h}},
volume = {{3}},
year = {{2005}},
}