title: Bioengineered human heparin with anticoagulant activity.
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 25mM 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.
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: m.lord@unsw.edu.au.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Lord
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Bill
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Fengying
authors.initials: F
authors.lastname: Tang
authors.affiliation: Sydney Head and Neck Cancer Institute, Cancer Services, Royal Prince Alfred Hospital, Sydney, Australia; Discipline of Dermatology, Bosch Institute, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia; Immune Imaging Division, Centenary Institute, Sydney, NSW 2050, Australia.
authors.forename: J Guy
authors.initials: JG
authors.lastname: Lyons
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Rnjak-Kovacina
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: John M
authors.initials: JM
authors.lastname: Whitelock
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D005818:Genetic Engineering / Q000379:methods*; D057809:HEK293 Cells; D006493:Heparin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D060847:Metabolic Engineering; D011509:Proteoglycans / Q000008:administration & dosage* / Q000096:biosynthesis* / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000008:administration & dosage* / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000925:Anticoagulants; D011509:Proteoglycans; D033921:Vesicular Transport Proteins; C036090:heparin proteoglycan; C075430:serglycin; D006493:Heparin
keywords: Glycosaminoglycan; Heparin; Proteoglycan; Recombinant expression; Serglycin