University of Edinburgh
Joseph Black Building
David Brewster Road
0131 650 4742
The structure elucidation of compounds contained within complex mixtures is a challenging task. We develop multidimensional NMR spectroscopy and mass spectrometry methods, in combination with chemical modification schemes, to investigate the most complex mixtures on earth: humic substances (HS) - heterogeneous mixtures containing thousands of organic molecules produced by the degradation of plant and animal residues.
In collaboration with The Scotch Whisky Research Institute we are also using NMR and MS to study notably more pleasant mixtures.
Carbohydrate structures and protein-carbohydrate interactions
Glycosaminoglycans isolated from marine environment are complex, heterogeneous polysaccharides that represent a considerable challenge for the NMR structure determination. We study their structure in collaboration with GlycoMar.
We study conformation of carbohydrates using scalar and residual dipolar coupling constants (image on the left, below). We also investigate the protein-carbohydrate interactions and study complexes between glycosaminoglycans and selectins, aswell as proteins of the complement (image on the right, below).
Using our 400 to 800 MHz NMR spectrometers equipped with cryoprobes we are developing NMR methodologies applicable for chemical and biological applications. In particular, we will be focussing on the development of new NMR tools for interrogation of chemical reactions and processes, studying reaction mechanism and kinetics of chemical reactions.
Bell, N.G.A., Michalchuk, A. A.L., Blackburn, J. W. T., Graham, M.C., Uhrín, D., Isotope-Filtered 4D NMR Spectroscopy for Structure Determination of Humic Substances. Angew. Chem. Int. Ed. 54, 8382 –8385 (2015).
Blaum, B.S., Hannan, J.P., Herbert, A.P., Kavanagh, D., Uhrín, D, Stehle, T. Structural basis for sialic acid-mediated self-recognition by complement factor H, Nature Chem. Biol. 11, 77–82 (2015).
Bell, N.G.A., Murray, L., Graham, M., Uhrín, D., NMR methodology for complex mixture ‘separation’. Chem. Commun. 50, 1694-1697 (2014).
Panagos, C.G., Thomson, D.S., Moss, C., Hughes, A.D., Kelly, M.S., Liu, Y., Chai, W., Venkatasamy, R., Spina, D., Page, C.P., Hogwood, J., Woods, R.J., Mulloy, B., Bavington, C.D., Uhrín, D. Fucosylated chondroitin sulfates from the body wall of the sea cucumber Holothuria forskali. Conformation, selectin binding and biological activity. J. Biol. Chem. 289, 28284–28298 (2014).
Bell, N.G.A, Rigg, G., Masters, S., Bella, J., Uhrín, D. Detecting low-level flexibility using residual dipolar couplings: a study of the conformation of cellobiose, Phys. Chem. Chem. Phys.15, 18223-18234 (2013).