Recent chemical and enzymatic approaches to the synthesis of glycosaminoglycan oligosaccharides.
Glycosaminoglycans, highly charged polycarboxylated, polysulfated polysaccharides, are an important class of therapeutic agents and investigational drug candidates. Heparin has been widely used as a clinical anticoagulant for over 60 years. Low molecular weight heparins have begun to displace heparin and recently a synthetic heparin pentasaccharide was approved for clinical use in Europe. In addition to heparin (and the related heparan sulfate glycosaminoglycan), dermatan sulfate, chondroitin sulfate, hyaluronan and their derivatives are all in various stages of clinical evaluation. This review focuses on the chemical and chemoenzymatic synthesis of glycosaminoglycan oligosaccharides. Recent advances in functional group protection chemistry, conversion of D-gluco to L-ido or D-galacto configurations, glycosylation reactions and the preparation and use of novel starting materials in acidic oligosaccharide synthesis are discussed.
Karst
Nathalie A
NA
Division of Medicinal and Natural Products Chemistry, Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, USA.
Linhardt
Robert J
RJ
D002240:Carbohydrate Sequence; D002809:Chondroitin Sulfates / Q000138:chemical synthesis; D003871:Dermatan Sulfate / Q000138:chemical synthesis; D006025:Glycosaminoglycans / Q000138:chemical synthesis*; D006493:Heparin / Q000138:chemical synthesis; D006497:Heparan Sulfate / Q000138:chemical synthesis; D006820:Hyaluronic Acid / Q000138:chemical synthesis; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis*
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D009844:Oligosaccharides