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Double Affinity Amplification of Galectin-Ligand Interactions through Arginine-Arene Interactions: Synthetic, Thermodynamic, and Computational Studies with Aromatic Diamido-Thiodigalactosides.

Cumpstey, Ian LU ; Salomonsson, Emma LU ; Sundin, Anders LU ; Leffler, Hakon LU and Nilsson, Ulf LU (2008) In Chemistry: A European Journal 14(14). p.4233-4245
Abstract
A series of aromatic mono- or diamido-thiodigalactoside derivatives were synthesized and studied as ligands for galectin-1, -3, -7, -8N terminal domain, and -9N terminal domain. The affinity determination in vitro with competitive fluorescence-polarization experiments and thermodynamic analysis by isothermal microcalorimetry provided a coherent picture of structural requirements for arginine-arene interactions in galectin-ligand binding. Computational studies were employed to explain binding preferences for the different galectins. Galectin-3 formed two almost ideal arene-arginine stacking interactions according to computer modeling and also had the highest affinity for the diamido-thiodigalactosides (K(d) below 50 nM). Site-directed... (More)
A series of aromatic mono- or diamido-thiodigalactoside derivatives were synthesized and studied as ligands for galectin-1, -3, -7, -8N terminal domain, and -9N terminal domain. The affinity determination in vitro with competitive fluorescence-polarization experiments and thermodynamic analysis by isothermal microcalorimetry provided a coherent picture of structural requirements for arginine-arene interactions in galectin-ligand binding. Computational studies were employed to explain binding preferences for the different galectins. Galectin-3 formed two almost ideal arene-arginine stacking interactions according to computer modeling and also had the highest affinity for the diamido-thiodigalactosides (K(d) below 50 nM). Site-directed mutagenesis of galectin-3 arginines involved in binding corroborated the importance of their interaction with the aromatic diamido-thiodigalactosides. Furthermore, the arginine mutants revealed distinct differences between free, flexible, and solvent-exposed arginine side chains and tightly ion-paired arginine side chains in interactions with aromatic systems. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
carbohydrates, galectin, inhibitors, thioglycosides
in
Chemistry: A European Journal
volume
14
issue
14
pages
4233 - 4245
publisher
John Wiley & Sons
external identifiers
  • pmid:18366047
  • wos:000256131800012
  • scopus:46749132784
ISSN
1521-3765
DOI
10.1002/chem.200701932
language
English
LU publication?
yes
id
25d57b00-b6ac-4af2-a500-eea3894a7eef (old id 1052149)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18366047?dopt=Abstract
date added to LUP
2008-05-12 12:52:51
date last changed
2017-08-27 04:41:16
@article{25d57b00-b6ac-4af2-a500-eea3894a7eef,
  abstract     = {A series of aromatic mono- or diamido-thiodigalactoside derivatives were synthesized and studied as ligands for galectin-1, -3, -7, -8N terminal domain, and -9N terminal domain. The affinity determination in vitro with competitive fluorescence-polarization experiments and thermodynamic analysis by isothermal microcalorimetry provided a coherent picture of structural requirements for arginine-arene interactions in galectin-ligand binding. Computational studies were employed to explain binding preferences for the different galectins. Galectin-3 formed two almost ideal arene-arginine stacking interactions according to computer modeling and also had the highest affinity for the diamido-thiodigalactosides (K(d) below 50 nM). Site-directed mutagenesis of galectin-3 arginines involved in binding corroborated the importance of their interaction with the aromatic diamido-thiodigalactosides. Furthermore, the arginine mutants revealed distinct differences between free, flexible, and solvent-exposed arginine side chains and tightly ion-paired arginine side chains in interactions with aromatic systems.},
  author       = {Cumpstey, Ian and Salomonsson, Emma and Sundin, Anders and Leffler, Hakon and Nilsson, Ulf},
  issn         = {1521-3765},
  keyword      = {carbohydrates,galectin,inhibitors,thioglycosides},
  language     = {eng},
  number       = {14},
  pages        = {4233--4245},
  publisher    = {John Wiley & Sons},
  series       = {Chemistry: A European Journal},
  title        = {Double Affinity Amplification of Galectin-Ligand Interactions through Arginine-Arene Interactions: Synthetic, Thermodynamic, and Computational Studies with Aromatic Diamido-Thiodigalactosides.},
  url          = {http://dx.doi.org/10.1002/chem.200701932},
  volume       = {14},
  year         = {2008},
}