Heparosan-Derived Heparan Sulfate/Heparin-Like Compounds: One Kind of Potential Therapeutic Agents.
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: The capsular polysaccharide was isolated from Escherichia coli 010:K5:H4; it could not be obtained from a uncapsulated (K5-) mutant. It contains N-acetylglucosamine and glucuronic acid in a molar ratio of 1:1. Acid hydrolysis of the acidic polysaccharide as well as Smith degradation and degradation by deamination of the carboxyl-reduced polysaccharide suggested that the polysaccharide is composed of a disaccharide repeating unit. The data obtained by methylation analysis and nuclear magnetic resonance spectroscopy indicated that the repeating sequence of the capsular polysaccharide is the 4-beta-glucuronyl-1,4-alpha-N-acetylglucosaminyl unit. This structure is similar to that of desulfo-heparin.European Journal of Biochemistry 06/1981; 116(2):359-64. · 3.58 Impact Factor
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ABSTRACT: The nucleotide sequence of region 2 of the Escherichia coli K5 capsule gene cluster has been determined. This region, essential for the biosynthesis of the K5 polysaccharide, contained four genes, termed kfiA-D. The G + C ratio was 33.4%, which was lower than the typical G + C ratio for E. coli and that of the flanking regions 1 and 3 in the K5 capsule gene cluster. Three major RNA transcripts were detected within region 2 by Northern blotting and three promoters located by transcript mapping. Promoter activity was confirmed by promoter-probe analysis. The predicted amino acid sequence of KfiC had homology to a number of glycosyl transferase enzymes and overexpression of the KfiC gene resulted in increased K5 transferase activity. The predicted amino acid sequence of KfiD had homology to a number of NAD-dependent dehydrogenase enzymes and was demonstrated to be a UDP-glucose dehydrogenase that catalyses the information of UDP-glucuronic acid from UDP-glucose.Molecular Microbiology 09/1995; 17(4):611-20. · 4.96 Impact Factor
- Endocrine Reviews 03/1997; 18(1):26-45. · 14.87 Impact Factor