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Synthesis, Biological Evaluation, WAC and NMR Studies of S ‐Galactosides and Non‐Carbohydrate Ligands of Cholera Toxin Based on Polyhydroxyalkylfuroate Moieties
Author(s) -
RamosSoriano Javier,
Niss Ulf,
Angulo Jesús,
Angulo Manuel,
MorenoVargas Antonio J.,
Carmona Ana T.,
Ohlson Sten,
Robina Inmaculada
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201302786
Subject(s) - cholera toxin , chemistry , galactose , glycosidic bond , stereochemistry , galactosides , toxin , ligand (biochemistry) , carbohydrate , ganglioside , biochemistry , receptor , biology , enzyme , microbiology and biotechnology
Abstract The synthesis of several non‐carbohydrate ligands of cholera toxin based on polyhydroxyalkylfuroate moieties is reported. Some of them have been linked to D ‐galactose through a stable and well‐tolerated S ‐glycosidic bond. They represent a novel type of non‐hydrolyzable bidentate ligand featuring galactose and polyhydroxyalkylfuroic esters as pharmacophoric residues, thus mimicking the GM1 ganglioside. The affinity of the new compounds towards cholera toxin was measured by weak affinity chromatography (WAC). The interaction of the best candidates with this toxin was also studied by saturation transfer difference NMR experiments, which allowed identification of the binding epitopes of the ligands interacting with the protein. Interestingly, the highest affinity was shown by non‐carbohydrate mimics based on a polyhydroxyalkylfuroic ester structure.