Heparin: Past, Present, and Future.
Heparin: Past, Present, and Future.
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DOI：
10.3390/ph9030038
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发表时间：
2016-07-04
期刊：
影响因子：
--
通讯作者：
Sharfstein ST
中科院分区：
文献类型：
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作者：
Oduah EI;Linhardt RJ;Sharfstein ST
肝素是当今世界上使用最广泛的抗凝血药物，它仍然是一种动物源性产品，存在掺假和污染的风险。2007-2008年的污染危机增加了提供在cGMP条件下生产的非动物来源肝素的动力。此外，最近的研究表明，肝素可能具有显著的抗肿瘤活性，独立于其抗凝血活性，而其他研究表明肝素在治疗炎症、不孕症和传染病方面发挥作用。已经提出了多种生产生物工程肝素的策略。在这篇综述中，我们讨论了几种这些策略，包括微生物生产，哺乳动物细胞生产和化学酶修饰。我们还提出了创造具有各种生化和生理特性的“设计”肝素和肝素-硫酸盐的策略。
Heparin, the most widely used anticoagulant drug in the world today, remains an animal-derived product with the attendant risks of adulteration and contamination. A contamination crisis in 2007–2008 increased the impetus to provide non-animal-derived sources of heparin, produced under cGMP conditions. In addition, recent studies suggest that heparin may have significant antineoplastic activity, separate and distinct from its anticoagulant activity, while other studies indicate a role for heparin in treating inflammation, infertility, and infectious disease. A variety of strategies have been proposed to produce a bioengineered heparin. In this review, we discuss several of these strategies including microbial production, mammalian cell production, and chemoenzymatic modification. We also propose strategies for creating “designer” heparins and heparan-sulfates with various biochemical and physiological properties.