Yu Yanlei, Fu Li, He Peng, Xia Ke, Varghese Sony, Wang Hong, Zhang Fuming, Dordick Jonathan, Linhardt Robert J
College of Pharmaceutical Science & Collaborative Innovation Center for Yangtze River Delta Region Green Pharmaceuticals, Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, 310014 Hangzhou, People's Republic of China.
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York 12180, United States.
ACS Chem Biol. 2022 Mar 18;17(3):637-646. doi: 10.1021/acschembio.1c00928. Epub 2022 Feb 24.
Heparin products are widely used clinical anticoagulants essential in the practice of modern medicine. Low-molecular-weight heparins (LMWHs) are currently prepared by the controlled chemical or enzymatic depolymerization of unfractionated heparins (UFHs) that are extracted from animal tissues. In many clinical applications, LMWHs have displaced UFHs and currently comprise over 60% of the heparin market. In the past, our laboratory has made extensive efforts to prepare bioengineered UFHs relying on a chemoenzymatic process to address concerns about animal-sourced UFHs. The current study describes the use of a novel chemoenzymatic process to prepare a chemobiosynthetic LMWH from a low-molecular-weight heparosan. The resulting chemobiocatalytic LMWH matches most of the United States pharmacopeial specifications for enoxaparin, a LMWH prepared through the base-catalyzed depolymerization of animal-derived UFH.
肝素产品是现代医学实践中广泛使用的临床抗凝剂。低分子量肝素（LMWHs）目前是通过对从动物组织中提取的普通肝素（UFHs）进行可控化学或酶解聚来制备的。在许多临床应用中，低分子量肝素已取代了普通肝素，目前占肝素市场的60%以上。过去，我们实验室曾做出大量努力，依靠化学酶法制备生物工程化普通肝素，以解决对动物源普通肝素的担忧。当前的研究描述了使用一种新型化学酶法从低分子量乙酰肝素制备化学合成低分子量肝素的过程。所得的化学生物催化低分子量肝素符合美国药典中关于依诺肝素的大部分规格要求，依诺肝素是一种通过动物源普通肝素的碱催化解聚制备的低分子量肝素。
