Session Speaker

Prospects of Drug Discovery by NMR Enhanced by Dynamic Nuclear Polarization
Geoffrey Bodenhausen
France

Nuclear magnetic resonance (NMR) has long been recognized as a powerful tool for drug research, in particular of the identification of small drug molecules that can inhibit the function of selected proteins. The Achilles’ heel of NMR is its poor sensitivity, but dynamic nuclear polarization (DNP) can greatly alleviate this problem. An overview will be given of recent progress in the field of ‘dissolution DNP’ to enhance NMR signals in solution by factors up to 10’000, as well as ‘gyrotron DNP’ which can boost NMR signals in solids by factors up to 100. We have been able to ‘hyphenate’ DNP with other methods by (1) extending the memory of long-lived singlet states in liquids to study slow exchange processes; (2) determining slow diffusion coefficients of protein complexes; (3) transferring information from slowly-relaxing nitrogen-15 to protons in choline and its metabolites; and (4) determining quadrupolar couplings of nitrogen-14 by indirect detection in solids.

References:

(1) Singlet-State Exchange NMR Spectroscopy for the Study of Very Slow Dynamic Processes, R. Sarkar, P. R. Vasos, and G. Bodenhausen, J. Am. Chem. Soc., 129, 328-334 (2007).

(2) Singlet States Open the Way to Longer Time-Scales in the Measurement of Diffusion by NMR Spectroscopy, S. Cavadini and P. Vasos, Concepts Magn. Reson., 32A, 68-78 (2008).

(3) Proton NMR of 15N-Choline Metabolites Enhanced by Dynamic Nuclear Polarization, R. Sarkar, A. Comment, P. Vasos, S. Jannin, R. Gruetter, G. Bodenhausen, H. Hall, D. Kirik, and V. Denisov, J. Am. Chem. Soc., in press (2009).

(4) Evidence for Dynamics on a 100 ns Time-Scale from Single- and Double-Quantum Nitrogen-14 NMR in Solid Peptides, S. Cavadini, A. Abraham, S. Ulzega, and G. Bodenhausen, J. Am. Chem. Soc., 130, 10850-10851 (2008).