Developing drugs from sugars: Current state of glycosaminoglycan- derived therapeutics

Sulfated glycosaminoglycans (GAGs) such as heparin and heparan sulfate (HS) are linear glycans consisting of 1,4-linked uronic acid and glucosamine (Figure 11.1) and encompassing varying degrees of sulfation (Gandhi and Mancera 2008). The HS and heparin, a minor ubiquitous form of HS, are polydisperse, polyanionic polysaccharides in which the negative charges arise from the presence of sulfate and carboxylate groups. These molecules found inside the cell and in the extracellular matrix (ECM) have manifold regulatory functions and are critically relevant to many disease processes, such as inflammation (Parish 2006), neurodegeneration (Díaz-Nido et al. 2002), angiogenesis (Iozzo and San Antonio 2001), cardiovascular disorders (Rosenberg et al. 1997), cancer (Yip et al. 2006), and infectious diseases (Rostand and Esko 1997).