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Stegmayr, John, Lepur, Adriana, Kahl-Knutson, Barbro, Aguilar-Moncayo, Matilde, Klyosov, Anatole A., Field, Robert A. 
ORCID: https://orcid.org/0000-0001-8574-0275, Oredsson, Stina, Nilsson, Ulf J. and Leffler, Hakon
(2016)
Low or no inhibitory potency of the canonical galectin carbohydrate-binding site by pectins and galactomannans.
Journal of Biological Chemistry, 291 (25).
pp. 13318-13334.
ISSN 0021-9258
Abstract
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 carbohydratebinding site.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by the European Community Seventh Framework Programme (FP7-2007-2013) under Grant HEALTH-F2-2011-256986 (PANACREAS) (to J. S.), FP6 Project "EuroPharm" Grant 043682 (to A. L.), Swedish Research Council Grant 621-2009-5656 (to H. L.) and 621-2003-4265 (to U. J. N.), Knut and Alice Wallenberg Foundation, Sweden (to H. L., U. J. N., and J. S.), United Kingdom Biotechnology and Biological Sciences Research Council Institute Strategic Programme Grant on Understanding and Exploiting Metabolism BB/J004561/1, and the John Innes Foundation (to M. A. and R. A. F.). A. A. K. is a shareholder in Galectin Therapeutics Inc., the company that owns the intellectual property for Davanat®.U.J.N.and H. L. are shareholders in Galecto Biotech AB, a company that develops galectin inhibitors (e.g. 33DFTG). |
| Uncontrolled Keywords: | biochemistry,molecular biology,cell biology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1303 |
| Faculty \ School: | Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 04 Sep 2024 13:34 |
| Last Modified: | 25 Sep 2024 18:06 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96528 |
| DOI: | 10.1074/jbc.M116.721464 |
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