Chemobiocatalytic Synthesis of a Low-Molecular-Weight Heparin
Authors:
Yanlei Yu, Li Fu, Peng He, Ke Xia, Sony Varghese, Hong Wang, Fuming Zhang*, Jonathan Dordick*, Robert J. Linhardt*
Affiliation:
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
Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, United States
Department of Biology and Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, United States
Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, United States
Description:
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.