title: Comparison of Low-Molecular-Weight Heparins Prepared From Bovine Lung Heparin and Porcine Intestine Heparin.
abstract: Currently porcine intestine is the only approved source for producing pharmaceutical heparin in most countries. Enoxaparin, prepared by benzylation and alkaline depolymerization from porcine intestine heparin, is prevalent in the anticoagulant drug market. It is predicted that porcine intestine heparin-derived enoxaparin (PIE) will encounter shortage, and expanding its production from heparins obtained from other animal tissues may, therefore, be inevitable. Bovine lung heparin is a potential alternative source for producing enoxaparin. Critical processing parameters for producing bovine lung heparin-derived enoxaparin (BLE) are discussed. Three batches of BLEs were prepared and their detailed structures were compared with PIEs using modern analytical techniques, including disaccharide composition, intact chain mapping by liquid chromatography-mass spectrometry and 2-dimensional nuclear magnetic resonance spectroscopy. The results suggested that the differences between PIEs and BLEs mainly result from N-acetylation differences derived from the parent heparins. In addition, bioactivities of BLEs were about 70% of PIEs based on anti-factor IIa and Xa chromogenic assays. We conclude that BLE has the potential to be developed as an analogue of PIE, although some challenges still remain.
authors.affiliation: National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan, Shandong, China.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Guan
authors.affiliation: National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan, Shandong, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.affiliation: National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan, Shandong, China; Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Liu
authors.affiliation: National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan, Shandong, China.
authors.forename: Anran
authors.initials: A
authors.lastname: Sheng
authors.affiliation: National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan, Shandong, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180; Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180; Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.affiliation: National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan, Shandong, China. Electronic address: lianlichi@sdu.edu.cn.
authors.forename: Lianli
authors.initials: L
authors.lastname: Chi
mesh_terms: D000818:Animals; D002417:Cattle; D006493:Heparin / Q000032:analysis / Q000737:chemistry; D006495:Heparin, Low-Molecular-Weight / Q000032:analysis* / Q000737:chemistry*; D007413:Intestinal Mucosa / Q000737:chemistry*; D007422:Intestines / Q000737:chemistry; D008168:Lung / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013552:Swine
chemical_list: D006495:Heparin, Low-Molecular-Weight; D006493:Heparin
keywords: LC-MS; NMR spectroscopy; bioanalysis; bovine lung; enoxaparin; glycosaminoglycans; heparin; molecular weight determination; porcine intestine; processing