Abstract
Hyaluronan (HA), a polyanionic polysaccharide consisting of repeating glucuronate and N-acetylglucosamine residues, exists surrounded by ions in its physiological milieu. For example, the average concentration of sodium is 300 mM in bovine hyaline cartilage, or roughly twice that of typical extracellular fluid [1]. It has been shown that salts can modify strongly the properties of HA [2,3] and its constituent monomers [4,5]. For example, Van Damme et al. [2] reported that binding of HA to lysozyme is most efficient at pH 7.5 and 10-15 mM NaCI. Self-association of hyaluronate segments in aqueous solution requires a sodium concentration of 150 mM [3]. Several physical techniques (NMR [6-13], X-ray [14-17], CD [8,18], and IR [9,14]) have been employed to determine if salts interact with uronate residues non-specifically (via electrostatic interaction) [7] or through chelation by several ligands acting in concert. Most authors have postulated the existence of chelation sites. A review of studies conducted on HA in the solid and liquid states leads to the conclusion that the oxygens of the carboxyl groups on HA and of water molecules always take part in coordination of metal cations, while other oxygens around the sugar ring are sometimes involved as well. The type of
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