Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-09-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/14/9/170 |
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| author | Jun-hui Li Shan Li Zi-jian Zhi Lu-feng Yan Xing-qian Ye Tian Ding Lei Yan Robert John Linhardt Shi-guo Chen |
| author_facet | Jun-hui Li Shan Li Zi-jian Zhi Lu-feng Yan Xing-qian Ye Tian Ding Lei Yan Robert John Linhardt Shi-guo Chen |
| author_sort | Jun-hui Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T12:43:12Z |
| format | Article |
| id | doaj.art-7d12ca7e6dd541aeb8bf24f30bf72a55 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T12:43:12Z |
| publishDate | 2016-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-7d12ca7e6dd541aeb8bf24f30bf72a552022-12-22T04:23:26ZengMDPI AGMarine Drugs1660-33972016-09-0114917010.3390/md14090170md14090170Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting FragmentsJun-hui Li0Shan Li1Zi-jian Zhi2Lu-feng Yan3Xing-qian Ye4Tian Ding5Lei Yan6Robert John Linhardt7Shi-guo Chen8Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, ChinaZhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, ChinaZhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, ChinaZhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, ChinaZhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, ChinaZhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, ChinaCenter for Biotechnology & Interdisciplinary Studies, Department of Chemistry & Chemical Biology, Rensselaer Polytechnic Institute, Biotechnology Center 4005, Troy, NY 12180, USACenter for Biotechnology & Interdisciplinary Studies, Department of Chemistry & Chemical Biology, Rensselaer Polytechnic Institute, Biotechnology Center 4005, Troy, NY 12180, USAZhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, ChinaFucosylated 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.http://www.mdpi.com/1660-3397/14/9/170sea cucumberfucosylated chondroitin sulfatefree-radical depolymerizationanticoagulant activity |
| spellingShingle | Jun-hui Li Shan Li Zi-jian Zhi Lu-feng Yan Xing-qian Ye Tian Ding Lei Yan Robert John Linhardt Shi-guo Chen Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments Marine Drugs sea cucumber fucosylated chondroitin sulfate free-radical depolymerization anticoagulant activity |
| title | Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments |
| title_full | Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments |
| title_fullStr | Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments |
| title_full_unstemmed | Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments |
| title_short | Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments |
| title_sort | depolymerization of fucosylated chondroitin sulfate with a modified fenton system and anticoagulant activity of the resulting fragments |
| topic | sea cucumber fucosylated chondroitin sulfate free-radical depolymerization anticoagulant activity |
| url | http://www.mdpi.com/1660-3397/14/9/170 |
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