Monday, December 11, 2017

Real-Time Analysis of Folding upon Binding of a Disordered Protein by Using Dissolution DNP NMR Spectroscopy #DNPNMR


Ragavan, M., et al., Real-Time Analysis of Folding upon Binding of a Disordered Protein by Using Dissolution DNP NMR Spectroscopy. Angew Chem Int Ed Engl, 2017. 56(25): p. 7070-7073.


The kinase inhibitory domain of the cell cycle regulatory protein p27(Kip1) (p27) was nuclear spin hyperpolarized using dissolution dynamic nuclear polarization (D-DNP). While intrinsically disordered in isolation, p27 adopts secondary structural motifs, including an alpha-helical structure, upon binding to cyclin-dependent kinase 2 (Cdk2)/cyclin A. The sensitivity gains obtained with hyperpolarization enable the real-time observation of (13) C NMR signals during p27 folding upon binding to Cdk2/cyclin A on a time scale of several seconds. Time-dependent intensity changes are dependent on the extent of folding and binding, as manifested in differential spin relaxation. The analysis of signal decay rates suggests the existence of a partially folded p27 intermediate during the timescale of the D-DNP NMR experiment.

Friday, December 8, 2017

In Situ Characterization of Pharmaceutical Formulations by Dynamic Nuclear Polarization Enhanced MAS NMR #DNPNMR


Ni, Q.Z., et al., In Situ Characterization of Pharmaceutical Formulations by Dynamic Nuclear Polarization Enhanced MAS NMR. The Journal of Physical Chemistry B, 2017. 121(34): p. 8132-8141.


A principal advantage of magic angle spinning (MAS) NMR spectroscopy lies in its ability to determine molecular structure in a noninvasive and quantitative manner. Accordingly, MAS should be widely applicable to studies of the structure of active pharmaceutical ingredients (API) and formulations. However, the low sensitivity encountered in spectroscopy of natural abundance APIs present at low concentration has limited the success of MAS experiments. Dynamic nuclear polarization (DNP) enhances NMR sensitivity and can be used to circumvent this problem provided that suitable paramagnetic polarizing agent can be incorporated into the system without altering the integrity of solid dosages. Here, we demonstrate that DNP polarizing agents can be added in situ during the preparation of amorphous solid dispersions (ASDs) via spray drying and hot-melt extrusion so that ASDs can be examined during drug development. Specifically, the dependence of DNP enhancement on sample composition, radical concentration, relaxation properties of the API and excipients, types of polarizing agents and proton density, has been thoroughly investigated. Optimal enhancement values are obtained from ASDs containing 1% w/w radical concentration. Both polarizing agents TOTAPOL and AMUPol provided reasonable enhancements. Partial deuteration of the excipient produced 3× higher enhancement values. With these parameters, an ASD containing posaconazole and vinyl acetate yields a 32-fold enhancement which presumably results in a reduction of NMR measurement time by ∼1000. This boost in signal intensity enables the full assignment of the natural abundance pharmaceutical formulation through multidimensional correlation experiments.

Wednesday, December 6, 2017

A sub-Kelvin cryogen-free EPR system


This article has nothing to do with DNP. However, the article nicely describes an impressive piece of isntrumentation to reach very low temperatures.


Melhuish, S.J., et al., A sub-Kelvin cryogen-free EPR system. J. Magn. Reson., 2017. 282(Supplement C): p. 83-88.


We present an EPR instrument built for operation at Q band below 1K. Our cryogen-free Dewar integrates with a commercial electro-magnet and bridge. A description of the cryogenic and RF systems is given, along with the adaptations to the standard EPR experiment for operation at sub-Kelvin temperatures. As a first experiment, the EPR spectra of powdered Cr12O9(OH)3(O2CCMe3)15 were measured. The sub-Kelvin EPR spectra agree well with predictions, and the performance of the sub-Kelvin system at 5K is compared to that of a commercial spectrometer.

Tuesday, December 5, 2017

[NMR] HYP18 meeting, Southampton Sep 2-5, 2018 #DNPNMR

This is advance notice of an international meeting on hyperpolarization, HYP18, which will be held in Southampton, UK on Sep 2-5, 2018

The program will cover a wide range of hyperpolarization techniques and their applications, including DNP in both liquids and solids, parahydrogen-based techniques, optical pumping, quantum rotor polarization, and other methods. We hope that the meeting will promote comparison, discussion, and cross-fertilisation between the different techniques. 

Confirmed speakers include:

Stephan Appelt, Aachen, Germany
Peter Blümler, Mainz, Germany
Kevin Brindle, Cambridge, UK
Arnaud Comment, Cambridge, UK
Bob Griffin, MIT, USA
Meghan Halse, York, UK
Sami Jannin, Lyon, France
Fedor Jelezko, Ulm, Germany
John Kurhanewicz, San Francisco, USA
Mathilde Lerche, Copenhagen, Denmark
Anne Lesage, Lyon, France
Gaël de Paëpe, Grenoble, France
Marek Pruski, Iowa, USA
Leif Schröder, Berlin, Germany
Thomas Theis, North Carolina, USA

Registration will open in january. 
So bookmark the link: www.southampton.ac.uk/hyp18
and pencil the dates in your diaries!

Malcolm Levitt and Giuseppe Pileio

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HYP18
Hyperpolarized Magnetic Resonance
Southampton UK, Sep 2-5 2018
——————————————————
Prof Malcolm Levitt
School of Chemistry
Room 27:2026
University of Southampton
Southampton SO17 1BJ
England.
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Monday, December 4, 2017

Photo-induced radical polarization and liquid-state dynamic nuclear polarization with fullerene nitroxide derivatives

DNP without microwave radiation? A very interesting approach.


Liu, G., et al., Photo-induced radical polarization and liquid-state dynamic nuclear polarization with fullerene nitroxide derivatives. Phys. Chem. Chem. Phys., 2017.


We report on radical polarization and optically-driven liquid DNP with nitroxide radicals functionalized by photoexcitable fullerene derivatives. Pulse laser excitation of the fullerene moiety leads to a transient nitroxide radical polarization that is one order of magnitude larger than at Boltzmann equilibrium. Life time of radical polarization increases with size of the fullerene derivative and correlates with the electronic spin lattice relaxation time T1e. Overhauser NMR signal enhancements of toluene solvent protons were observed under steady-state illumination, which replaced microwave irradiation.

Wednesday, November 29, 2017

Dynamic nuclear polarization for sensitivity enhancement in modern solid-state NMR #DNPNMR


Lilly Thankamony, A.S., et al., Dynamic nuclear polarization for sensitivity enhancement in modern solid-state NMR. Prog Nucl Magn Reson Spectrosc, 2017. 102-103(Supplement C): p. 120-195.


The field of dynamic nuclear polarization has undergone tremendous developments and diversification since its inception more than 6 decades ago. In this review we provide an in-depth overview of the relevant topics involved in DNP-enhanced MAS NMR spectroscopy. This includes the theoretical description of DNP mechanisms as well as of the polarization transfer pathways that can lead to a uniform or selective spreading of polarization between nuclear spins. Furthermore, we cover historical and state-of-the art aspects of dedicated instrumentation, polarizing agents, and optimization techniques for efficient MAS DNP. Finally, we present an extensive overview on applications in the fields of structural biology and materials science, which underlines that MAS DNP has moved far beyond the proof-of-concept stage and has become an important tool for research in these fields.

[NMR] Assistant Professor in Experimental Magnetic Resonance at University of Florida / National High Magnetic…

From the Ampere Magnetic Resonance List

As part of a major faculty hiring initiative, the Department of Chemistry at the University of Florida (http://www.chem.ufl.edu ) seeks a full-time, nine-month, tenure-track appointment at the level of ASSISTANT PROFESSOR, in the general area of magnetic resonance, broadly defined, to begin August 16, 2018. The successful applicant will join over 40 Faculty in the Department, which is home to the Quantum Theory Project and the Butler Polymer Research Center. The Department has recently opened the Joseph Hernandez Hall, a state-of-the-art teaching and research facility. Numerous opportunities exist for collaboration across the UF campus and the National High Magnetic Field Laboratory (NHMFL; https://nationalmaglab.org/ ) and the Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) Facility. The new faculty member will be expected to develop a successful research program that utilizes or develops magnetic resonance methodology, preferably with applications at high magnetic fields. UF and the Department of Chemistry are committed to increasing faculty diversity and candidates from under-represented groups are particularly encouraged to apply. The university and greater Gainesville community enjoy a diversity of cultural events, restaurants, year-round outdoor recreational activity, and social opportunities.

Applications must be submitted through Careers at UF at http://explore.jobs.ufl.edu/cw/en-us/listing/ (search job 505531) and include: a cover letter, curriculum vitae, description of future research plans and teaching philosophy (3 pages maximum combined), and contact information for at least three references. After initial review, letters of recommendation will be requested for short listed applicants. Inquiries can be addressed to the Chair of the search committee (Professor Gail Fanucci fanucci@chem.ufl.edu), Department of Chemistry, University of Florida, P.O. Box 117200, Gainesville, FL 32611-7200. Review of applications will begin December 1, 2017, and continue until the position is filled. The University of Florida is an equal opportunity institution. If an accommodation due to a disability is needed to apply for this position, please call (352) 392-2477 or the Florida Relay System at (800) 955-8771 (TDD). The selection process will be conducted under the provisions of Florida's "Government in the Sunshine" and Public Records laws.


Joanna R. Long, PhD
Associate Professor of Biochemistry & Molecular Biology
Director, Advanced Magnetic Resonance Imaging & Spectroscopy Facility
Assoc. Director, National High Magnetic Field Laboratory

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