CHONDROITIN SULFATE AS A BIOACTIVE MACROMOLECULE FOR ADVANCED BIOLOGICAL APPLICATIONS AND THERAPIES

Glycosaminoglycans (GAGs) are acidic, highly sulfated, complex, linear, natural heteropolysaccharides
distributed among all organisms and composed of a variable number
of repeating disaccharide units. Each disaccharide consists of one hexosamine, Dgalactosamine
(GalN) or D-glucosamine (GlcN), and one uronic acid, D-glucuronic
acid (GlcA) or L-iduronic acid (IdoA) or neutral hexose, D-galactose (Gal). According
to the type of the monosaccharide units and the glycosidic bonds between them,
GAGs can be divided into four main categories: (1) hyaluronic acid or hyaluronan
(HA); (2) chondroitin sulfate (CS) and dermatan sulfate (DS); (3) heparan sulfate
(HS) and heparin (Hep); and (4) keratan sulfate (KS) (Fig. 5.1). GAGs are present
in all animals and some of them like Hep, CS and DS are extracted from terrestrial
and marine soft tissues and cartilages for therapeutic uses. They are synthesized as
polymers of repeating disaccharides with an N-acetyl-hexosamine (GalNAc or Glc-
NAc) as one of the sugars. The alternating sugar is GlcA with the exception of KS
which contains galactose instead. HA, very peculiar because it is neither sulfated nor
covalently linked to a protein, containing GlcNAc, is not further modified, whereas
the other classes are modified by: (1) the addition of O-sulfate groups on various
hydroxyls (the three classes); (2) 5-epimerization of someGlcA residues to form IdoA
residues (DS, HS, Hep); and (3) removal of acetyl residues from some hexosamines