Low or No Inhibitory Potency of the Canonical Galectin Carbohydrate-binding Site by Pectins and Galactomannans
| Autor: | Matilde Aguilar-Moncayo, Adriana Lepur, Hakon Leffler, John Stegmayr, Anatole A. Klyosov, Robert A. Field, Ulf J. Nilsson, Stina Oredsson, Barbro Kahl-Knutson |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
animal structures Galectins Glycobiology and Extracellular Matrices Antineoplastic Agents Fluorescence Polarization fluorescence anisotropy Polysaccharide Biochemistry Mannans Inhibitory Concentration 50 03 medical and health sciences chemistry.chemical_compound Galactomannan glycobiology Polysaccharides Cell Line Tumor Manchester Institute of Biotechnology otorhinolaryngologic diseases Humans Binding site Molecular Biology Galectin pectin chemistry.chemical_classification Binding Sites galectin davanat Hemagglutination Galactose Cell Biology Carbohydrate Oligosaccharide Galactan ResearchInstitutes_Networks_Beacons/manchester_institute_of_biotechnology 3. Good health stomatognathic diseases 030104 developmental biology chemistry pectasol polysaccharide galactomannan Pectins cancer therapy hemagglutination Drug Screening Assays Antitumor Protein Binding |
| Zdroj: | Stegmayr, J, Lepur, A, Kahl-Knutson, B, Aguilar-Moncayo, M, Klyosov, A A, Field, R A, Oredsson, S, Nilsson, U J & Leffler, H 2016, ' Low or No Inhibitory Potency of the Canonical Galectin Carbohydrate-binding Site by Pectins and Galactomannans ', Journal of Biological Chemistry . https://doi.org/10.1074/jbc.M116.721464 The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m116.721464 |
| Popis: | Some complex plant-derived polysaccharides, such as modified citrus pectins and galactomannans, have been shown to have promising anti-inflammatory and anti-cancer effects. Most reports propose or claim that these effects are due to interaction of the polysaccharides with galectins because the polysaccharides contain galactose-containing side chains that might bind this class of lectin. However, their direct binding to and/or inhibition of the evolutionarily conserved galactoside-binding site of galectins has not been demonstrated. Using a well established fluorescence anisotropy assay, we tested the direct interaction of several such polysaccharides with physiological concentrations of a panel of galectins. The bioactive pectic samples tested were very poor inhibitors of the canonical galactoside-binding site for the tested galectins, with IC50 values >10 mg/ml for a few or in most cases no inhibitory activity at all. The galactomannan Davanat® was more active, albeit not a strong inhibitor (IC50 values ranging from 3 to 20 mg/ml depending on the galectin). Pure synthetic oligosaccharide fragments found in the side chains and backbone of pectins and galactomannans were additionally tested. The most commonly found galactan configuration in pectins had no inhibition of the galectins tested. Galactosylated tri- and pentamannosides, representing the structure of Davanat®, had an inhibitory effect of galectins comparable with that of free galactose. Further evaluation using cell-based assays, indirectly linked to galectin-3 inhibition, showed no inhibition of galectin-3 by the polysaccharides. These data suggest that the physiological effects of these plant polysaccharides are not due to inhibition of the canonical galectin carbohydrate-binding site. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|