Interaction of cartilage proteoglycans with hyaluronic acid. The role of the hyaluronic acid carboxyl groups

Abstract

Hyaluronic acid [umbilical cord]-derived oligomers of 5-15 repeat disaccharides effectively bind to bovine nasal-cartilage proteoglycan and inhibit interaction between proteoglycans and high-molecular-weight hyaluronic acid. If the hyaluronic acid oligosaccharides are modified by reaction with diazomethane to form the carboxyl methyl esters of the glucuronic acid residues, their inhibitory activity is abolished. Binding capacity can be fully restored by saponification. The amide derivative, which is formed by condensation of the oligosaccharide carboxyl groups with glycine methyl ester, is ineffective in blocking the proteoglycan-hyaluronic acid interaction. In this case, binding activity is not restored when the amidated oligomers are subjected to saponification to yield the free carboxylate groups on the glycine residues. The displacement of the carboxylate groups on the polysaccharide chain by interposition of a glycine residue blocks the interaction between the proteoglycans and hyaluronic acid oligomers. When the oligosaccharide methyl ester is reduced with NaBH4, the resultant glucose-containing oligomers exhibit decreased binding to proteoglycans. The hyaluronic acid carboxylate anion in a specific spatial orientation may be required for hyaluronic acid-proteoglycan interaction.