title: Low or No Inhibitory Potency of the Canonical Galectin Carbohydrate-binding Site by Pectins and Galactomannans.
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 carbohydrate-binding site.
authors.affiliation: From the Section MIG (Microbiology, Immunology, Glycobiology), Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden, the Department of Biology and john.stegmayr@med.lu.se.
authors.forename: John
authors.identifier: 0000-0002-8167-9259
authors.initials: J
authors.lastname: Stegmayr
authors.affiliation: From the Section MIG (Microbiology, Immunology, Glycobiology), Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden.
authors.forename: Adriana
authors.initials: A
authors.lastname: Lepur
authors.affiliation: From the Section MIG (Microbiology, Immunology, Glycobiology), Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden.
authors.forename: Barbro
authors.initials: B
authors.lastname: Kahl-Knutson
authors.affiliation: the Department of Biological Chemistry, John Innes Centre, Norwich Research Park, NR4 7UH Norwich, United Kingdom, and.
authors.forename: Matilde
authors.initials: M
authors.lastname: Aguilar-Moncayo
authors.affiliation: Galectin Therapeutics, Newton, Massachusetts 02459.
authors.forename: Anatole A
authors.initials: AA
authors.lastname: Klyosov
authors.affiliation: the Department of Biological Chemistry, John Innes Centre, Norwich Research Park, NR4 7UH Norwich, United Kingdom, and.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Field
authors.affiliation: the Department of Biology and.
authors.forename: Stina
authors.initials: S
authors.lastname: Oredsson
authors.affiliation: Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Lund, Sweden.
authors.forename: Ulf J
authors.initials: UJ
authors.lastname: Nilsson
authors.affiliation: From the Section MIG (Microbiology, Immunology, Glycobiology), Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden, hakon.leffler@med.lu.se.
authors.forename: Hakon
authors.identifier: 0000-0003-4482-8945
authors.initials: H
authors.lastname: Leffler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005454:Fluorescence Polarization; D005690:Galactose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D037161:Galectins / Q000737:chemistry*; D006384:Hemagglutination; D006801:Humans; D020128:Inhibitory Concentration 50; D008351:Mannans; D010368:Pectins / Q000737:chemistry* / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding
chemical_list: D000970:Antineoplastic Agents; D037161:Galectins; D008351:Mannans; D011134:Polysaccharides; C012990:galactomannan; D010368:Pectins; D005690:Galactose
keywords: cancer therapy; davanat; fluorescence anisotropy; galactomannan; galectin; glycobiology; hemagglutination; pectasol; pectin; polysaccharide