25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Signal-improved real-time NMR spectroscopy of proteins by hyperpolarized water

30 Aug 2019, 11:30
25m
Lecture Hall A (Henry Ford Building)

Lecture Hall A

Henry Ford Building

Talk Hyperpolarization techniques Hyperpolarization

Speaker

Prof. Dennis Kurzbach (University of Vienna)

Description

Hyperpolarized water produced by dissolution dynamic nuclear polarization (dDNP) has recently been shown to enable the detection of hyperpolarized spectra of proteins with up to 300-fold improvement in signal amplitudes. With this dDNP approach, novel insights can be gained into solvent accessible surfaces, ligand interactions, and complex protein geometries. Examples of applications to host-ligand systems including peptides and folded as well as intrinsically disordered proteins (IDPs) have demonstrated the broad applicability of the hyperpolarized water approach. [1-5]

In this contribution, we present recent efforts to combine dDNP with real-time NMR, aimed at tracking protein-ligand binding events and protein-solvent interactions at a sub-Hertz sampling rate. Two applications will be presented: (1) The use of hyperpolarized water to examine the kinetics underlying protein-ligand interactions. Here, non-equilibrium dynamics in the osteopontin-heparin host-ligand system were monitored in a dDNP experiment by simultaneous mixing of the protein with the ligand and hyperpolarized water. (2) A proof-of-concept for real-time protein dDNP at residue-resolution at hand of Ubiquitin in hyperpolarized water by a statistical analysis of time-series of 1D dDNP spectra.

References
1. P. Kaderavek, F. Ferrage, G. Bodenhausen and D. Kurzbach, Chem. Eur. J., 2018, 24, 13418-13423.
2. O. Szekely, G. L. Olsen, I. C. Felli and L. Frydman, Anal Chem, 2018, 90, 10, 6169-6177.
3. D. Kurzbach, E. Canet, A. G. Flamm, A. Jhajharia, E. M. Weber, R. Konrat and G. Bodenhausen, Angew Chem Int Ed Engl, 2017, 56, 389-392.
4. G. Olsen, E. Markhasin, O. Szekely, C. Bretschneider and L. Frydman, J Magn Reson, 2016, 264, 49-58.
5. G. L. Olsen, O. Szekely, B. Mateos, P. Kadeřávek, F. Ferrage, R. Konrat, R. Pierattelli, I. C. Felli, G. Bodenhausen, D. Kurzbach and L. Frydman, 2019, in preparation.

Primary authors

Prof. Dennis Kurzbach (University of Vienna) Dr Gregory L Olsen (Unvirsity of Vienna)

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