Depolymerization of Fucosylated chondroitin sulfate with a modified fenton-system and anticoagulant activity of the resulting fragments

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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43 Scopus citations

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.

Original languageEnglish
Article number170
JournalMarine Drugs
Volume14
Issue number9
DOIs
StatePublished - Sep 2016
Externally publishedYes

Keywords

  • Anticoagulant activity
  • Free-radical depolymerization
  • Fucosylated chondroitin sulfate
  • Sea cucumber

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