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 (1)H, (13)C and (15)N nuclei in hyaluronan oligosaccharides with seven different naturally occurring terminal rings. At 900MHz, all (1)H nuclei in the hexasaccharide GlcA-β-(1→3)-GlcNAc-β-(1→4)-GlcA-β-(1→3)-GlcNAc-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.
coupling constant, resolution, hyaluronan, strong coupling, end-effect
NCBI PubMed ID: 17056022Publication DOI: 10.1016/j.carres.2006.09.023Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: andrew.almond@manchester.ac.uk
Institutions: Faculty of Life Sciences, Manchester Interdisciplinary Biocentre, University of Manchester, Princess Street, Manchester M1 7DN, UK, The Henry Wellcome Building for Biomolecular NMR Spectroscopy, CR-UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK
Methods: NMR
Found