A galactoside-binding protein tricked into binding unnatural pyranose derivatives : 3-deoxy-3-methyl-gulosides selectively inhibit galectin-1
(2019) In International Journal of Molecular Sciences 20(15).- Abstract
Galectins are a family of galactoside-recognizing proteins involved in different galectin-subtype-specific inflammatory and tumor-promoting processes, which motivates the development of inhibitors that are more selective galectin inhibitors than natural ligand fragments. Here, we describe the synthesis and evaluation of 3-C-methyl-gulopyranoside derivatives and their evaluation as galectin inhibitors. Methyl 3-deoxy-3-C-(hydroxymethyl)-β-d-gulopyranoside showed 7-fold better affinity for galectin-1 than the natural monosaccharide fragment analog methyl β-d-galactopyranoside, as well as a high selectivity over galectin-2, 3, 4, 7, 8, and 9. Derivatization of the 3-C-hydroxymethyl into amides gave gulosides with improved selectivities and... (More)
Galectins are a family of galactoside-recognizing proteins involved in different galectin-subtype-specific inflammatory and tumor-promoting processes, which motivates the development of inhibitors that are more selective galectin inhibitors than natural ligand fragments. Here, we describe the synthesis and evaluation of 3-C-methyl-gulopyranoside derivatives and their evaluation as galectin inhibitors. Methyl 3-deoxy-3-C-(hydroxymethyl)-β-d-gulopyranoside showed 7-fold better affinity for galectin-1 than the natural monosaccharide fragment analog methyl β-d-galactopyranoside, as well as a high selectivity over galectin-2, 3, 4, 7, 8, and 9. Derivatization of the 3-C-hydroxymethyl into amides gave gulosides with improved selectivities and affinities; methyl 3-deoxy-3-C-(methyl-2,3,4,5,6-pentafluorobenzamide)-β-d-gulopyranoside had Kd 700 µM for galectin-1, while not binding any other galectin.
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- author
- Pal, Kumar Bhaskar ; Mahanti, Mukul LU ; Leffler, Hakon LU and Nilsson, Ulf J. LU
- organization
- publishing date
- 2019-08-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Benzamide, Fluorescence polarization, Galectin-1, Gulopyranosides, Selective
- in
- International Journal of Molecular Sciences
- volume
- 20
- issue
- 15
- article number
- 3786
- publisher
- MDPI AG
- external identifiers
-
- scopus:85070972252
- pmid:31382488
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms20153786
- language
- English
- LU publication?
- yes
- id
- 3f36c04e-e64e-4d32-9882-f62eaa571d23
- date added to LUP
- 2019-09-09 11:42:21
- date last changed
- 2024-04-16 19:06:58
@article{3f36c04e-e64e-4d32-9882-f62eaa571d23,
abstract = {{<p>Galectins are a family of galactoside-recognizing proteins involved in different galectin-subtype-specific inflammatory and tumor-promoting processes, which motivates the development of inhibitors that are more selective galectin inhibitors than natural ligand fragments. Here, we describe the synthesis and evaluation of 3-C-methyl-gulopyranoside derivatives and their evaluation as galectin inhibitors. Methyl 3-deoxy-3-C-(hydroxymethyl)-β-d-gulopyranoside showed 7-fold better affinity for galectin-1 than the natural monosaccharide fragment analog methyl β-d-galactopyranoside, as well as a high selectivity over galectin-2, 3, 4, 7, 8, and 9. Derivatization of the 3-C-hydroxymethyl into amides gave gulosides with improved selectivities and affinities; methyl 3-deoxy-3-C-(methyl-2,3,4,5,6-pentafluorobenzamide)-β-d-gulopyranoside had K<sub>d</sub> 700 µM for galectin-1, while not binding any other galectin.</p>}},
author = {{Pal, Kumar Bhaskar and Mahanti, Mukul and Leffler, Hakon and Nilsson, Ulf J.}},
issn = {{1661-6596}},
keywords = {{Benzamide; Fluorescence polarization; Galectin-1; Gulopyranosides; Selective}},
language = {{eng}},
month = {{08}},
number = {{15}},
publisher = {{MDPI AG}},
series = {{International Journal of Molecular Sciences}},
title = {{A galactoside-binding protein tricked into binding unnatural pyranose derivatives : 3-deoxy-3-methyl-gulosides selectively inhibit galectin-1}},
url = {{http://dx.doi.org/10.3390/ijms20153786}},
doi = {{10.3390/ijms20153786}},
volume = {{20}},
year = {{2019}},
}