Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments |
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Authors: | Jun-hui Li Shan Li Zi-jian Zhi Lu-feng Yan Xing-qian Ye Tian Ding Lei Yan Robert John Linhardt Shi-guo Chen |
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Affiliation: | 1Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, China; (J.L.); (S.L.); (Z.Z.); (L.Y.); (X.Y.); (T.D.);2Center for Biotechnology & Interdisciplinary Studies, Department of Chemistry & Chemical Biology, Rensselaer Polytechnic Institute, Biotechnology Center 4005, Troy, NY 12180, USA; (L.Y.); (R.J.L.) |
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Abstract: | Fucosylated chondroitin sulfate (fCS) from sea cucumber Isostichopus badionotus (fCS-Ib) with a chondroitin sulfate type E (CSE) backbone and 2,4-O-sulfo fucose branches has shown excellent anticoagulant activity although has also show severe adverse effects. Depolymerization represents an effective method to diminish this polysaccharide’s side effects. The present study reports a modified controlled Fenton system for degradation of fCS-Ib and the anticoagulant activity of the resulting fragments. Monosaccharides and nuclear magnetic resonance (NMR) analysis of the resulting fragments indicate that no significant chemical changes in the backbone of fCS-Ib and no loss of sulfate groups take place during depolymerization. A reduction in the molecular weight of fCS-Ib should result in a dramatic decrease in prolonging activated partial thromboplastin time and thrombin time. A decrease in the inhibition of thrombin (FIIa) by antithromin III (AT III) and heparin cofactor II (HCII), and the slight decrease of the inhibition of factor X activity, results in a significant increase of anti-factor Xa (FXa)/anti-FIIa activity ratio. The modified free-radical depolymerization method enables preparation of glycosaminoglycan (GAG) oligosaccharides suitable for investigation of clinical anticoagulant application. |
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Keywords: | sea cucumber fucosylated chondroitin sulfate free-radical depolymerization anticoagulant activity |
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