Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments

Abstract

Fucosylated chondroitin sulfate (fCS) from sea cucumber <i>Isostichopus badionotus</i> (fCS-<i>Ib</i>) with a chondroitin sulfate type E (CSE) backbone and 2,4-<i>O</i>-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-<i>Ib</i> 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-<i>Ib</i> and no loss of sulfate groups take place during depolymerization. A reduction in the molecular weight of fCS-<i>Ib</i> 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.