Studies of arginine-arene interactions through synthesis and evaluation of a series of galectin-binding aromatic lactose esters
(2007) In ChemBioChem 8(12). p.1389-1398- Abstract
- Aromatic lactose 2-O-esters were synthesized and used to probe arene-arginine interactions with the galectin family of proteins. They were found to be low mu m inhibitors of galectin-1, -3, and -9N-terminal domain and moderate inhibitors of galectin-7, but not inhibitors of galectin-8N-terminal, which locks an arginine residue close to the critical, esterified lactose 2-O-position. Molecular modeling of galectins in complex with aromatic lactose 2-O-esters, as well as binding studies with a galectin-3 R186S mutant, confirmed that the inhibitory efficiency of the lactose 2-O-esters was due to the formation of strong interactions between the aromatic ester moieties and the arginine guanidinium groups of galectin-1 and -3. An important common... (More)
- Aromatic lactose 2-O-esters were synthesized and used to probe arene-arginine interactions with the galectin family of proteins. They were found to be low mu m inhibitors of galectin-1, -3, and -9N-terminal domain and moderate inhibitors of galectin-7, but not inhibitors of galectin-8N-terminal, which locks an arginine residue close to the critical, esterified lactose 2-O-position. Molecular modeling of galectins in complex with aromatic lactose 2-O-esters, as well as binding studies with a galectin-3 R186S mutant, confirmed that the inhibitory efficiency of the lactose 2-O-esters was due to the formation of strong interactions between the aromatic ester moieties and the arginine guanidinium groups of galectin-1 and -3. An important common feature shared by galectin-1 and -3 was that the arginines formed in-plane ion pairs with two side-chain carboxylates, which resulted in extended planar pi-electron surfaces that did not require solvation by water; these surfaces were ideal for stocking with aromatic moieties of the ligands. The results provide a basis for the design of lectin inhibitors and drugs that exploit interactions with arginine side-chains via aromatic moieties, which are involved in intramolecular protein salt bridges. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/689584
- author
- Cumpstey, Ian LU ; Salomonsson, Emma LU ; Sundin, Anders LU ; Leffler, Hakon LU and Nilsson, Ulf LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- inhibitors, galectin, cation-pi interaction, arenes, carbohydrates
- in
- ChemBioChem
- volume
- 8
- issue
- 12
- pages
- 1389 - 1398
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000248851700011
- scopus:34548118303
- ISSN
- 1439-4227
- DOI
- 10.1002/cbic.200700040
- 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
- c14e4450-6997-4f3a-ac55-92b0ecdad95d (old id 689584)
- date added to LUP
- 2016-04-01 12:19:19
- date last changed
- 2022-01-27 02:01:44
@article{c14e4450-6997-4f3a-ac55-92b0ecdad95d,
abstract = {{Aromatic lactose 2-O-esters were synthesized and used to probe arene-arginine interactions with the galectin family of proteins. They were found to be low mu m inhibitors of galectin-1, -3, and -9N-terminal domain and moderate inhibitors of galectin-7, but not inhibitors of galectin-8N-terminal, which locks an arginine residue close to the critical, esterified lactose 2-O-position. Molecular modeling of galectins in complex with aromatic lactose 2-O-esters, as well as binding studies with a galectin-3 R186S mutant, confirmed that the inhibitory efficiency of the lactose 2-O-esters was due to the formation of strong interactions between the aromatic ester moieties and the arginine guanidinium groups of galectin-1 and -3. An important common feature shared by galectin-1 and -3 was that the arginines formed in-plane ion pairs with two side-chain carboxylates, which resulted in extended planar pi-electron surfaces that did not require solvation by water; these surfaces were ideal for stocking with aromatic moieties of the ligands. The results provide a basis for the design of lectin inhibitors and drugs that exploit interactions with arginine side-chains via aromatic moieties, which are involved in intramolecular protein salt bridges.}},
author = {{Cumpstey, Ian and Salomonsson, Emma and Sundin, Anders and Leffler, Hakon and Nilsson, Ulf}},
issn = {{1439-4227}},
keywords = {{inhibitors; galectin; cation-pi interaction; arenes; carbohydrates}},
language = {{eng}},
number = {{12}},
pages = {{1389--1398}},
publisher = {{John Wiley & Sons Inc.}},
series = {{ChemBioChem}},
title = {{Studies of arginine-arene interactions through synthesis and evaluation of a series of galectin-binding aromatic lactose esters}},
url = {{http://dx.doi.org/10.1002/cbic.200700040}},
doi = {{10.1002/cbic.200700040}},
volume = {{8}},
year = {{2007}},
}