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

Institute of Biochemical and Biotechnological Drug & National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China.
Medicinal Research Reviews (Impact Factor: 9.58). 04/2012; DOI: 10.1002/med.21263
Source: PubMed

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. © 2012 Wiley Periodicals, Inc. Med. Res. Rev., 00, No. 00, 1-28, 2012.

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    ABSTRACT: Introduction: Heparan sulfate (HS) is a polysaccharide that is ubiquitously expressed on the cell surface and in the extracellular matrix and interacts with a wide variety of proteins to mediate numerous biological and pathological functions, including inflammation. Areas covered: The structural diversity and the multiple biological roles of HS in inflammation are discussed. HS is involved in the recruitment and attachment of leukocytes to the inflamed epithelium, the activation of chemokines and the transmigration of leukocytes to the underlying target tissue. The endoglycosidase heparanase plays a key role in the above processes via the degradation of HS. HS mimetics that inhibit heparanase and block HS-binding proteins have been shown to inhibit inflammation in multiple animal models. Expert opinion: HS plays important roles in many stages of the inflammation process, in particular the regulation of leukocyte extravasation. Compounds that can inhibit HS-protein interactions thus have considerable potential as anti-inflammatory therapeutics capable of simultaneously interfering with multiple steps of the inflammation process. There are a number of such compounds in various stages of clinical development for cancer, which should also find applications in inflammatory illnesses.
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