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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)
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author
; ; ; and
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
Wiley-Blackwell
external identifiers
  • pmid:18366047
  • wos:000256131800012
  • pmid:18366047
  • scopus:44749094652
ISSN
1521-3765
DOI
10.1002/chem.200701932
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: Division of Microbiology, Immunology and Glycobiology - MIG (013025200), Organic chemistry (S/LTH) (011001240)
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
2016-04-01 13:40:52
date last changed
2022-08-29 03:51:59
@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}},
  keywords     = {{carbohydrates; galectin; inhibitors; thioglycosides}},
  language     = {{eng}},
  number       = {{14}},
  pages        = {{4233--4245}},
  publisher    = {{Wiley-Blackwell}},
  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}},
  doi          = {{10.1002/chem.200701932}},
  volume       = {{14}},
  year         = {{2008}},
}