The glycosaminoglycan hyaluronan is involved in a diverse range of physiological and diseases processes and comprises repeated disaccharide units of N-acetyl-d-glucosamine (GlcNAc) and d-glucuronic acid (GlcA). A molecular description of the solution conformation of HA is required to account for this biology, which is best attained using nuclear magnetic resonance (NMR). NMR studies of the polymer, however, are frustrated by resonance overlap arising from the highly degenerate structure. In contrast, end-effects in oligosaccharides can produce some chemical shift dispersion, giving the possibility that their conformational properties can be measured and extrapolated to models of the polymer. We report the complete resolution and assignment of 1H, 13C and 15N nuclei in hyaluronan oligosaccharides with seven different naturally occurring terminal rings. At 900 MHz, all 1H nuclei in the hexasaccharide GlcA-β-(1→3)-GlcNAc-β-(1→4)-GlcA-β-(1→3)-G lcNAc-β-(1→4)-GlcA-β-(1→3)-GlcNAc-OH were uniquely resolved and the two central rings were found to be a good model for the polymer environment. These assignments now allow resolved, unambiguous structural restraints to be acquired on this oligosaccharide and extrapolated to models for the solution conformation of the polymer. © 2006 Elsevier Ltd. All rights reserved.
- Coupling constant
- Strong coupling
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Opening the door to ligand-based drug discovery: a rapid and accurate technology for determining bioactive 3D molecular shapes
Andrew Almond (Participant) & Charles Blundell (Participant)
Impact: Economic impacts, Health impacts, Technological impacts