Lord Megan S, Cheng Bill, Tang Fengying, Lyons J Guy, Rnjak-Kovacina Jelena, Whitelock John M
Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
Metab Eng. 2016 Nov;38:105-114. doi: 10.1016/j.ymben.2016.07.006. Epub 2016 Jul 18.
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.
肝素是一种临床上用于预防血栓形成的碳水化合物抗凝剂，然而杂质会限制其疗效。在此，我们报告了通过人细胞中重组表达人丝甘蛋白来生物合成类肝素硫酸乙酰肝素的方法。表达的丝甘蛋白还带有硫酸软骨素/硫酸皮肤素链，并且这些糖胺聚糖链的相对丰度在培养基中不同葡萄糖浓度下会发生变化。发现在培养基中存在25mM葡萄糖时重组表达的丝甘蛋白具有的抗凝活性是猪未分级肝素的七分之一，这表明生物工程化的人源类肝素硫酸乙酰肝素可能是一种安全的下一代药用肝素。
