Synthesis,Biological Evaluation,WAC and NMR Studies of S‐Galactosides and Non‐Carbohydrate Ligands of Cholera Toxin Based on Polyhydroxyalkylfuroate Moieties |
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| Authors: | Javier Ramos‐Soriano Ulf Niss Dr Jesús Angulo Dr Manuel Angulo Dr Antonio J Moreno‐Vargas Dr Ana T Carmona Prof Dr Sten Ohlson Prof Dr Inmaculada Robina |
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| Institution: | 1. Department of Organic Chemistry, Faculty of Chemistry, University of Seville, Prof. García González 1, 41012 Seville (Spain), Fax: (+34)?954624960;2. Department of Chemistry and Biomedical Sciences, Linnaeus University, 391 82 Kalmar (Sweden);3. Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), CSIC and University of Seville, Americo Vespucio 49, 41092 Seville (Spain);4. Current address: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ (UK);5. Centro de Investigación Tecnológica e Innovación (CITIUS), University of Seville, Avda Reina Mercedes s/n, 41012 Seville (Spain) |
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| 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. |
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| Keywords: | weak affinity chromatography (WAC) biomimetic synthesis carbohydrates cholera toxin NMR spectroscopy |
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