期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1820, 期 7, 页码 989-1000出版社
ELSEVIER
DOI: 10.1016/j.bbagen.2012.03.002
关键词
Sea cucumber; Fucan; ES-MS; NMR; Anticoagulant; Antithrombotic
资金
- International Science & Technology Cooperation Program of China [2010DFA31330]
- Marine Scientific Research and Specific Public Service Project [201105029, 201005024]
- National Natural Science Foundation of China [30871944, 30972284]
Background: The aim is to analyze the structure, anticoagulant and antithrombotic activities of a sulfated fucan isolated from sea cucumber Isostichopus badionotus (fucan-Ib). Methods: Fucan-Ib was hydrolyzed under mild acid conditions. The oligosaccharide fragments were fractionated by gel-filtration chromatography and the structures were determined by negative-ion electrospray tandem mass spectrometry with collision-induced dissociation and two-dimensional NMR. Anticoagulant activities were measured by activated partial thromboplastin, thrombin and prothrombin times, and by in vitro inhibition experiments with factors ha and Xa. Antithrombotic activities were determined in vitro by measuring the length and weight of the thrombus generated. Result: The linear polysaccharide sequence of fucan-Ib was deduced from the structures of its oligosaccharide fragments produced by acid hydrolysis. Under mild conditions, the glycosidic bonds between the non-sulfated and 2,4-O-disulfated fucose residues were selectively cleaved and highly ordered oligosaccharide fragments with a tetrasaccharide repeating unit [-> 3Fuc(2S,4S)alpha 1 -> 3Fuc(2S)alpha 1 -> 3Fuc(2S)alpha 1 -> 3Fuc alpha 1 ->](n) were obtained. In in vitro assays fucan-Ib showed good anticoagulant and antithrombotic activities compared with heparin and the fucosylated chondroitin sulfate isolated from the same source (fCS-Ib). The two polysaccharides, fucan-Ib and fCS-Ib, differ in the mechanism of action; the former exhibited activity mainly by potentiation of antithrombin acted on thrombin and factor Xa whereas the latter mainly through heparin cofactor II. Conclusion: Fucan-Ib has a well defined structure with tetrasaccharide tandem repeats and good anticoagulant and antithrombotic activities. General importance: Fucan-Ib has a well defined structure and can be readily quality-controlled, and therefore has potential therapeutic value as an affective antithrombotic drug with low risk of bleeding. (C) 2012 Elsevier B.V. All rights reserved.
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