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Tuning the Preference of Thiodigalactoside- and Lactosamine-Based Ligands to Galectin-3 over Galectin-1

van Hattum, Hilde; Branderhorst, Hilbert M.; Moret, Ed E.; Nilsson, Ulf LU ; Leffler, Hakon LU and Pieters, Roland J. (2013) In Journal of Medicinal Chemistry 56(3). p.1350-1354
Abstract
Inhibitors for galectin-1 and -3 were synthesized from thiodigalactoside and lactosamine by derivatization of the galactose C3. Introduction of 4-phenyl-1H-1,2,3-triazol-1-yl substituents at the thiodigalactoside C3 by CuAAC, targeting arginine-arene interactions, increased the affinity to 13 nM but yielded little selectivity. The builder 4-(4-phenoxypheny1)-1H-1,2,3-triazol-1-yl substituent, however, increased the preference for galectin-3 over galectin-1 to more than 200-fold. Modeling showed more arginine-arene interactions for galectin-3 than for galectin-1. Introducing 4-phenoxyaryl groups on lactosamine had a similar effect.
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medicinal Chemistry
volume
56
issue
3
pages
1350 - 1354
publisher
American Chemical Society (ACS)
external identifiers
  • wos:000315182100060
  • scopus:84873903645
ISSN
1520-4804
DOI
10.1021/jm301677r
language
English
LU publication?
yes
id
87790cbe-a99d-4579-82d9-12b0cfbddd2f (old id 3671227)
date added to LUP
2013-04-23 14:49:16
date last changed
2019-02-20 03:24:33
@article{87790cbe-a99d-4579-82d9-12b0cfbddd2f,
  abstract     = {Inhibitors for galectin-1 and -3 were synthesized from thiodigalactoside and lactosamine by derivatization of the galactose C3. Introduction of 4-phenyl-1H-1,2,3-triazol-1-yl substituents at the thiodigalactoside C3 by CuAAC, targeting arginine-arene interactions, increased the affinity to 13 nM but yielded little selectivity. The builder 4-(4-phenoxypheny1)-1H-1,2,3-triazol-1-yl substituent, however, increased the preference for galectin-3 over galectin-1 to more than 200-fold. Modeling showed more arginine-arene interactions for galectin-3 than for galectin-1. Introducing 4-phenoxyaryl groups on lactosamine had a similar effect.},
  author       = {van Hattum, Hilde and Branderhorst, Hilbert M. and Moret, Ed E. and Nilsson, Ulf and Leffler, Hakon and Pieters, Roland J.},
  issn         = {1520-4804},
  language     = {eng},
  number       = {3},
  pages        = {1350--1354},
  publisher    = {American Chemical Society (ACS)},
  series       = {Journal of Medicinal Chemistry},
  title        = {Tuning the Preference of Thiodigalactoside- and Lactosamine-Based Ligands to Galectin-3 over Galectin-1},
  url          = {http://dx.doi.org/10.1021/jm301677r},
  volume       = {56},
  year         = {2013},
}