Sequence determination and anticoagulant and antithrombotic activities of a novel sulfated fucan isolated from the sea cucumber Isostichopus badionotus
| Autor: | Xinqian Ye, Yaqin Hu, Changhu Xue, Guangli Yu, Shiguo Chen, Wengang Chai, Guoyun Li |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Spectrometry Mass Electrospray Ionization Magnetic Resonance Spectroscopy Stereochemistry Sea Cucumbers Molecular Sequence Data Biophysics Biochemistry Rats Sprague-Dawley Thrombin Polysaccharides Tandem Mass Spectrometry Antithrombotic medicine Animals Tetrasaccharide Isostichopus badionotus Blood Coagulation Molecular Biology Heparin cofactor II chemistry.chemical_classification biology Chemistry Antithrombin Anticoagulants Thrombosis Heparin Oligosaccharide biology.organism_classification Rats Carbohydrate Sequence Factor Xa Blood Coagulation Tests Sequence Analysis Factor Xa Inhibitors medicine.drug |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - General Subjects. 1820:989-1000 |
| ISSN: | 0304-4165 |
| Popis: | 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 IIa 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)α1→3Fuc(2S)α1→3Fuc(2S)α1→3Fucα1→]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. |
| Databáze: | OpenAIRE |
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