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Bioengineered human heparin with anticoagulant activity
Institution:1. Systems Biology and Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China;2. Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, China;3. Department of Cardiology, Affiliated Hospital of Qingdao University, Qingdao, China
Abstract:Heparin is a carbohydrate anticoagulant used clinically to prevent thrombosis, however impurities can limit its efficacy. Here we report the biosynthesis of heparin-like heparan sulfate via the recombinant expression of human serglycin in human cells. The expressed serglycin was also decorated with chondroitin/dermatan sulfate chains and the relative abundance of these glycosaminoglycan chains changed under different concentrations of glucose in the culture medium. The recombinantly expressed serglycin produced with 25 mM glucose present in the culture medium was found to possess anticoagulant activity one-seventh of that of porcine unfractionated heparin, demonstrating that bioengineered human heparin-like heparan sulfate may be a safe next-generation pharmaceutical heparin.
Keywords:Heparin  Serglycin  Proteoglycan  Glycosaminoglycan  Recombinant expression
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