AsianScientist (Jul. 2, 2015) – Research by a team from the Kunming Institute of Botany (KIB) of Chinese Academy of Sciences has identified a compound with potential as a novel anticoagulant due to its negligible bleeding risk: an oligosaccharide isolated from sea cucumbers. Their research has been published in the Proceedings of the National Academy of Sciences.
The discovery is significant since thrombotic disease—as one of the major causes of human death—is often treated with anticoagulants. However, almost all anticoagulants currently in use entail a severe risk of bleeding. Because intrinsic coagulant factors are necessary for thrombosis but not required for hemostasis, researchers have sought to develop new anticoagulants that selectively inhibit intrinsic coagulant factors.
Theoretically, intrinsic tenase is the final and rate-limiting enzyme complex in the intrinsic pathway of the blood coagulation cascade. It is an attractive but less explored target for developing new anticoagulants due to the lack of pure selective inhibitors.
In the present study, a team of researchers led by Professor Zhao Jinhua from KIB have purified a series of oligosaccharides with potent and selective inhibition for intrinsic tenase. The purified oligosaccharides particularly inhibit the intrinsic pathway, while having little effect on the extrinsic and common pathways of the blood coagulation cascade, highlighting the potential for the development of compounds for treatment of thrombotic disease.
In this research, compound 5 is the smallest compound among those oligosaccharides having strong anti-tenase activity. Using a rat venous thrombosis model, the researchers showed that the compound demonstrates significant antithrombotic activity, as strong as the most commonly used clinical drug, Enoxaparin.
Importantly, the compound has no significant effect on hemostatic function even at a high dose, whereas Enoxaparin is associated with significant hemorrhagic tendency. This result demonstrates the potential for development of a better drug in the near future. In addition, the finding is very useful for clarifying the difference between physiological hemostasis and pathological thrombosis.
The oligosaccharides were obtained from fucosylated glycosaminoglycan (FG), which is a natural product extracted from sea cucumber. However, the precise structure of native FG was not elucidated for many years due to the difficulty of conducting chemical research on complicated polysaccharides.
The article can be found at: Zhao et al. (2015) Discovery of an Intrinsic Tenase Complex Inhibitor: Pure Nonasaccharide from Fucosylated Glycosaminoglycan.
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Source: Chinese Academy of Sciences; Photo: Shutterstock.
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