Liu Xinyue, St Ange Kalib, Fareed Jawed, Hoppensteadt Debra, Jeske Walter, Kouta Ahmed, Chi Lianli, Jin Caijuan, Jin Yongsheng, Yao Yiming, Linhardt Robert J
1 Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, National Glycoengineering Research Center and State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong, China.
2 Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA.
Clin Appl Thromb Hemost. 2017 Sep;23(6):542-553. doi: 10.1177/1076029616686422. Epub 2017 Jan 5.
Heparin and its low-molecular-weight heparin (LMWH) derivatives are widely used clinical anticoagulants. These drugs are critical for the practice of medicine in applications including kidney dialysis, cardiopulmonary bypass, and in the management of venous thromboembolism. Currently, these drugs are derived from livestock, primarily porcine intestine. The worldwide dependence on a single animal species has made the supply chain for this critical drug quite fragile, leading to the search for other sources of these drugs, including bovine tissues such as bovine intestine or lung. A number of laboratories are currently examining the similarities and differences between heparins prepared from porcine and bovine tissues. The current study is designed to compare LMWH prepared from bovine heparins through chemical β-elimination, a process currently used to prepare the LMWH, enoxaparin, from porcine heparin. Using top-down, bottom-up, compositional analysis and bioassays, LMWHs, derived from bovine lung and intestine, are shown to closely resemble enoxaparin.
肝素及其低分子量肝素(LMWH)衍生物是临床广泛使用的抗凝剂。这些药物在包括肾脏透析、体外循环以及静脉血栓栓塞管理等医学应用中至关重要。目前,这些药物来源于家畜,主要是猪小肠。全球对单一动物物种的依赖使得这种关键药物的供应链相当脆弱,从而促使人们寻找这些药物的其他来源,包括牛组织,如牛肠或牛肺。目前许多实验室正在研究从猪组织和牛组织制备的肝素之间的异同。当前的研究旨在比较通过化学β消除法从牛肝素制备的低分子量肝素,这是目前用于从猪肝素制备低分子量肝素依诺肝素的过程。通过自上而下、自下而上、成分分析和生物测定,结果表明,源自牛肺和牛肠的低分子量肝素与依诺肝素非常相似。