High-Resolution 2D NMR of Disordered Proteins Enhanced by Hyperpolarized Water

Szekely, O., G. L. Olsen, I. C. Felli, and L. Frydman. “High-Resolution 2D NMR of Disordered Proteins Enhanced by Hyperpolarized Water.” Analytical Chemistry, March 26, 2018.


This study demonstrates the usefulness derived from relying on hyperpolarized water obtained by dissolution DNP, for site-resolved biophysical NMR studies of intrinsically disordered proteins. Thanks to the facile amide-solvent exchange experienced by protons in these proteins, 2D NMR experiments that like HMQC rely on the polarization of the amide protons, can be enhanced using hyperpolarized water by several orders of magnitude over their conventional counterparts. Optimizations of the DNP procedure and of the subsequent injection into the protein sample are necessary to achieve these gains while preserving state-of-the-art resolution; procedures enabling this transfer of the hyperpolarized water and the achievement of foamless hyperpolarized protein solutions are demonstrated. These protocols are employed to collect 2D (15)N-(1)H HMQC NMR spectra of alpha-synuclein, showing residue-specific enhancements >/=100x over their thermal counterparts. These enhancements, however, vary considerably throughout the residues. The biophysics underlying this residue-specific behavior upon injection of hyperpolarized water is theoretically examined, the information that it carries is compared with results arising from alternative methods, and its overall potential is discussed.

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