Recent Chemical and Enzymatic Approaches to the Synthesis of Glycosaminoglycan Oligosaccharides

Abstract

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.

Effect of Nonanimal High- and Low-Molecular-Mass Chondroitin Sulfates Produced by a Biotechnological Process in an Animal Model of Polyarthritis

“…In order to overcome the abovementioned drawbacks, several chemical/biotechnological approaches have been developed to produce CS of nonextractive origin, having structures and properties similar to the animal polysaccharide [11,12,13,14]. However, to date, no biological activity has ever been tested and confirmed for these nonextractive polysaccharides.…”

Antithrombin Activation by Nonsulfated, Non-Polysaccharide Organic Polymer

“…[5][6][7][8][9] Recently, major advances on chemoenzymatic front have been made to synthesize these small sulfated saccharides. [10][11][12][13][14] Likewise, some non-heparin molecules have also been investigated as antithrombotics. [15][16][17] These possess sulfated or phosphorylated thrombin binding domain that are non-heparin structures, but retain the highly sulfated DEFGH structure as the critical antithrombin binding domain.…”

Highly Efficient Syntheses of Hyaluronic Acid Oligosaccharides

“…[5,19] We plan to examine the alternative of using thioglycosides as building blocks, because thioglycosides are stable to most functional group transformation and yet can be easily activated by a wide range of thiophilic promoters. [32,33] Moreover, they can be conveniently stored on bench top for months without decomposition.…”

“…[5,19] In the first method, glucuronic acid building blocks are directly utilized to react with a glucosamine derivative. [20] The newly formed disaccharide was transformed into either an acceptor by selective deprotection or a glycosyl donor through aglycon adjustment.…”

“…[5,[19][20][21][22][23][24][25][26][27] To facilitate biological studies of sHA, a robust method needs to be developed so that fast and efficient assembly of multiple sHA can be achieved.…”