Dynamic nuclear polarization-enhanced 13C NMR spectroscopy of static biological solids

Published: Monday, 24 June 2013 - 14:00 UTC

Author:

Potapov, A., W.M. Yau, and R. Tycko, Dynamic nuclear polarization-enhanced (13)C NMR spectroscopy of static biological solids. J Magn Reson, 2013. 231(0): p. 5-14.

http://www.ncbi.nlm.nih.gov/pubmed/23562665

We explore the possibility of using dynamic nuclear polarization (DNP) to enhance signals in structural studies of biological solids by solid state NMR without sample spinning. Specifically, we use 2D (13)C-(13)C exchange spectroscopy to probe the peptide backbone torsion angles (varphi, psi) in a series of selectively (13)C-labeled 40-residue beta-amyloid (Abeta1-40) samples, in both fibrillar and non-fibrillar states. Experiments are carried out at 9.39T and 8K, using a static double-resonance NMR probe and low-power microwave irradiation at 264GHz. In frozen solutions of Abeta1-40 fibrils doped with DOTOPA-TEMPO, we observe DNP signal enhancement factors of 16-21. We show that the orientation- and frequency-dependent spin polarization exchange between sequential backbone carbonyl (13)C labels can be simulated accurately using a simple expression for the exchange rate, after experimentally determined homogeneous (13)C lineshapes are incorporated in the simulations. The experimental 2D (13)C-(13)C exchange spectra place constraints on the varphi and psi angles between the two carbonyl labels. Although the data are not sufficient to determine varphi and psi uniquely, the data do provide non-trivial constraints that could be included in structure calculations. With DNP at low temperatures, 2D (13)C-(13)C exchange spectra can be obtained from a 3.5mg sample of Abeta1-40 fibrils in 4h or less, despite the broad (13)C chemical shift anisotropy line shapes that are observed in static samples.