Heparosan-Derived Heparan Sulfate/Heparin-Like Compounds: One Kind of Potential Therapeutic Agents

Authors

  • Pingli Li,

    1. Institute of Biochemical and Biotechnological Drug & National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Shandong, China
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  • Juzheng Sheng,

    1. Institute of Biochemical and Biotechnological Drug & National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Shandong, China
    2. Division of Medicinal Chemistry and Natural Product, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, 27599, USA
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  • Yuhong Liu,

    1. Institute of Biochemical and Biotechnological Drug & National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Shandong, China
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  • Juan Li,

    1. Institute of Biochemical and Biotechnological Drug & National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Shandong, China
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  • Jian Liu,

    Corresponding author
    1. Division of Medicinal Chemistry and Natural Product, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, 27599, USA
    • Institute of Biochemical and Biotechnological Drug & National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Shandong, China
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  • Fengshan Wang

    Corresponding author
    • Institute of Biochemical and Biotechnological Drug & National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Shandong, China
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Correspondence to: Jian Liu, Division of Medicinal Chemistry and Natural Product, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA, E-mail:jian_liu@unc.edu

Fengshan Wang, School of Pharmaceutical Sciences, Shandong University, No.44, Wenhua Xilu, Jinan 250012, Shandong, China, E-mail: fswang@sdu.edu.cn

Abstract

Heparan sulfate (HS) is a highly sulfated glycosaminoglycan and exists in all animal tissues. HS and heparin are very similar, except that heparin has higher level of sulfation and higher content of iduronic acid. Despite the fact that it is a century-old drug, heparin remains as a top choice for treating thrombotic disorders. Pharmaceutical heparin is derived from porcine intestine or bovine lung via a long supply chain. This supply chain is vulnerable to the contamination of animal pathogens. Therefore, new methods for manufacturing heparin or heparin-like substances devoid of animal tissues have been explored by many researchers, among which, modifications of heparosan, the capsular polysaccharide of Escherichia coli K5 strain, is one of the promising approaches. Heparosan has a structure similar to unmodified backbone of natural HS and heparin. It is feasible to obtain HS or heparin derivatives by modifying heparosan with chemical or enzymatic methods. These derivatives display different biological activities, such as anticoagulant, anti-inflammatory, anticancer, and antiviral activities. This review focuses on the recent studies of synthesis, activity, and structure-activity relationship of HS/heparin-like derivatives prepared from heparosan.

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