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Design of biologically active heparan sulfate and heparin using an enzyme-based approach

  作者 Peterson, S; Frick, A; Liu, J  
  选自 期刊  Natural Product Reports ;  卷期  2009年26-5;  页码  610-627  
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[摘要]Heparan sulfate (HS) is a highly sulfated polysaccharide that plays essential physiological and pathophysiological roles. Heparin, a special form of HS, is a commonly used anticoagulant drug. The biosynthesis of HS involves numerous enzymes, including sulfotransferases, glycosyl transferases and an epimerase. It is widely believed that unique sulfation patterns of HS determine its specific functions. Thus, obtaining a series of HS structures with defined sulfation patterns is critical for elucidating the function-structure relationship of this important class of biomolecules. The chemical syntheses of such sulfated saccharides, especially molecules larger than an octasaccharide, are extremely difficult. Therefore, employing HS biosynthetic enzymes to synthesize HS that has the desired biological functions offers an attractive alternative. This review presents the recent progress on this approach. In addition, we discuss the mechanism used by HS sulfotransferases to recognize specific sulfated saccharide sequences. 186 References are cited.

 
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