Periodate oxidation and macromolecular compaction of hyaluronan*

Partial periodate oxidation of hyaluronan (HA) leads to ring opening of the 4-linked D-glucuronate (GlcA) residues, providing a particularly flexible element within otherwise semi-flexible chains. This leads to compaction of the chains as demonstrated by a pronounced decrease in the intrinsic persistence length, which was determined on the basis of the molecular weight dependence of radius of gyration (RG) and the intrinsic viscosity. These parameters were readily obtained using size-exclusion chromatography (SEC) with an online multi-angle laser light scattering (MALLS) detector, a viscosity detector, and a concentration-sensitive detector. The electrostatic contribution to the total persistence length increased with increasing degree of oxidation. Compared to alginates and chitosans, HA becomes less degraded during the oxidation, which is attributed to a protective effect of periodate-resistant N-acetyl-D-glucosamine (GlcNAc) residues adjacent to periodate-sensitive GlcA residues in HA.