Design of biologically active heparan sulfate and heparin using an enzyme-based approach.
Covering: up to August 2008. 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 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.
Peterson
Sherket
S
Division of Medicinal Chemistry and Natural Products, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Frick
Amber
A
Liu
Jian
J
D000925:Anticoagulants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002240:Carbohydrate Sequence; D015195:Drug Design; D006493:Heparin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006497:Heparan Sulfate / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008954:Models, Biological; D015394:Molecular Structure; D015238:Sulfotransferases / Q000378:metabolism*
D000925:Anticoagulants; D006493:Heparin; D006497:Heparan Sulfate; D015238:Sulfotransferases