Double Affinity Amplification of Galectin-Ligand Interactions through Arginine-Arene Interactions: Synthetic, Thermodynamic, and Computational Studies with Aromatic Diamido-Thiodigalactosides.
(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:
https://lup.lub.lu.se/record/1052149
- author
- Cumpstey, Ian LU ; Salomonsson, Emma LU ; Sundin, Anders LU ; Leffler, Hakon LU and Nilsson, Ulf LU
- organization
- publishing date
- 2008
- 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}},
}