Comparison of secondary structures in water of chondroitin-4-sulfate and dermatan sulfate: implications in the formation of tertiary structures.

Chondroitin-4-sulfate (CS4) and dermatan sulfate (DS) were examined in D2O solution, with or without NaCl, by NMR at 300 MHz, to investigate the physicochemical consequences of epimerization of glucuronate (GlcUA in CS4) to iduronate (IdoUA in DS). Nuclear Overhauser effects (NOEs) and spin-lattice relaxation times following selective and nonselective inversion were measured at up to 70 degrees C. (1) NOEs confirmed 4C1 conformations of sugar rings in N-acetylgalactosamine and GlcUA, and 1C4 or 2S0 in IdoUA. Conflict between NMR data and periodate oxidation kinetics over IdoUA conformations is resolvable by postulating conversion of monodentate periodate-1C4 complexes to conformations in which periodate oxidation can procede. (2) Pairs of glycosidic protons in CS4 and DS showed strong NOEs, implying that stretches of 2-fold helix were present, with carboxylate and acetamido groups close to each other on the same side of tapelike molecules, extending previous work in dimethyl sulfoxide solution. CS4 and DS have large hydrophobic patches in this configuration, similar to those in keratan sulfate and hyaluronan. (3) Selective and nonselective inversion-recoveries implied similar segmental and backbone mobilities and hence flexibilities in CS4 and DS. This is discussed in terms of intrinsic flexibility of glycosidic conformations, modified by hydrogen-bonded arrays. (4) We postulate that hydrophobic and hydrogen bonding drives DS self-aggregation. Stronger self-aggregation of DS compared with CS4 is attributed to increased intermolecular hydrogen-bonding in DS, secondary to decreased intramolecular hydrogen-binding. This is partly because the axial OH groups in 1C4 IdoUA cannot hydrogen-bond to neighboring sugars as can the equatorial OH groups in GlcUA of CS4.