title: Structural characterization and anti-inflammatory activity of two novel polysaccharides from the sea squirt, Ascidiella aspersa.
abstract: It is now recognized that certain polysaccharides can exhibit anti-inflammatory activity, including the glycosaminoglycan (GAG) heparin that is widely used as an anti-coagulant drug. However, it would be desirable to identify molecules that retain the anti-inflammatory actions of heparin, but that are devoid of significant anti-coagulant activity. In the present study we have identified a number of novel GAG and GAG-like polysaccharides (VRP327) from marine organisms, most of which were resistant to digestion by heparinase II and chondroitinase ABC. Fourier transform infra-red spectrum (FTIR) revealed species with variable degrees of sulphation and monosaccharide analysis revealed a range of sugar compounds, which in some cases included sugars not present in mammalian GAGs. (1)H NMR spectra of these species are consistent with the structures of complex polysaccharides. From an initial screening cascade to remove compounds having significant anti-coagulant activity and no overt cytotoxicity, we identified a high molecular weight oversulphated dermatan sulphate (VRP327) isolated from the tunicate Ascidiella aspersa which was fully characterised by NMR spectroscopy. This material was depolymerised to produce well characterized low molecular weight fractions which were demonstrated to be non-toxic, with low levels of anti-coagulant activity, and to have demonstrable anti-inflammatory activity assessed in several in vitro and in vivo models. The identification of low molecular weight polysaccharides having significant anti-inflammatory activity without significant anti-coagulant activity may provide novel templates for the development of a novel class of anti-inflammatory drugs.
authors.affiliation: GlycoMar Ltd, European Centre for Marine Biotechnology, Oban, Scotland PA37 1QA, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Thomson
authors.affiliation: EaStCHEM School of Chemistry, Joseph Black Building, The King's Buildings, Edinburgh EH9 3JJ, UK.
authors.forename: Charalampos G
authors.initials: CG
authors.lastname: Panagos
authors.affiliation: Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, SE1 9NH, UK.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Venkatasamy
authors.affiliation: GlycoMar Ltd, European Centre for Marine Biotechnology, Oban, Scotland PA37 1QA, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Moss
authors.affiliation: GlycoMar Ltd, European Centre for Marine Biotechnology, Oban, Scotland PA37 1QA, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Robinson
authors.affiliation: GlycoMar Ltd, European Centre for Marine Biotechnology, Oban, Scotland PA37 1QA, UK.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Bavington
authors.affiliation: Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, SE1 9NH, UK; National Institute for Biological Standards and Control, South Mimms, Herts EN6 3QG, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hogwood
authors.affiliation: Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, SE1 9NH, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mulloy
authors.affiliation: EaStCHEM School of Chemistry, Joseph Black Building, The King's Buildings, Edinburgh EH9 3JJ, UK.
authors.forename: Dušan
authors.initials: D
authors.lastname: Uhrín
authors.affiliation: Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, SE1 9NH, UK.
authors.forename: Domenico
authors.initials: D
authors.lastname: Spina
authors.affiliation: Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, SE1 9NH, UK. Electronic address: clive.page@kcl.ac.uk.
authors.forename: Clive P
authors.initials: CP
authors.lastname: Page
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000925:Anticoagulants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004195:Disease Models, Animal; D006025:Glycosaminoglycans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D011134:Polysaccharides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014561:Urochordata / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D006025:Glycosaminoglycans; D011134:Polysaccharides; D003871:Dermatan Sulfate
keywords: Adhesion; Elastase; Glycosaminoglycans; Inflammation; Marine organisms