Monday, February 27, 2017

Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water


Kurzbach, D., et al., Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water. Angew. Chem. Int. Ed., 2017. 56(1): p. 389-392.


Hyperpolarized water can selectively enhance NMR signals of rapidly exchanging protons in osteopontin (OPN), a metastasis-associated intrinsically disordered protein (IDP), at near-physiological pH and temperature. The transfer of magnetization from hyperpolarized water is limited to solvent-exposed residues and therefore selectively enhances signals in 1H-15N correlation spectra. Binding to the polysaccharide heparin was found to induce the unfolding of preformed structural elements in OPN.

Friday, February 24, 2017

Large dose hyperpolarized water with dissolution-DNP at high magnetic field


Lipsø, K.W., et al., Large dose hyperpolarized water with dissolution-DNP at high magnetic field. J. Magn. Reson., 2017. 274: p. 65-72.


We demonstrate a method for the preparation of hyperpolarized water by dissolution Dynamic Nuclear Polarization at high magnetic field. Protons were polarized at 6.7 T and 1.1 K to >70% with frequency modulated microwave irradiation at 188G Hz. 97.2 ± 0.7% of the radical was extracted from the sample in the dissolution in a two-phase system. 16 ± 1 mL of 5.0 M 1H in D2O with a polarization of 13.0 ± 0.9% in the liquid state was obtained, corresponding to an enhancement factor of 4000 ± 300 compared to the thermal equilibrium at 9.4 T and 293 K. A longitudinal relaxation time constant of 16 ± 1 s was measured. The sample was polarized and dissolved in a fluid path compatible with clinical polarizers. The volume of hyperpolarized water produced by this method enables angiography and perfusion measurements in large animals, as well as NMR experiments for studies of e.g. proton exchange and polarization transfer to other nuclei.

Wednesday, February 22, 2017

Theoretical treatment of pulsed Overhauser dynamic nuclear polarization: Consideration of a general periodic pulse sequence #DNPNMR


Nasibulov, E.A., et al., Theoretical treatment of pulsed Overhauser dynamic nuclear polarization: Consideration of a general periodic pulse sequence. JETP Letters, 2016. 103(9): p. 582-587.


A general theoretical approach to pulsed Overhauser-type dynamic nuclear polarization (DNP) is presented. Dynamic nuclear polarization is a powerful method to create non-thermal polarization of nuclear spins, thereby enhancing their nuclear magnetic resonance signals. The theory presented can treat pulsed microwave irradiation of electron paramagnetic resonance transitions for periodic pulse sequences of general composition. Dynamic nuclear polarization enhancement is analyzed in detail as a function of the microwave pulse length for rectangular pulses and pulses with finite rise time. Characteristic oscillations of the DNP enhancement are found when the pulse-length is stepwise increased, originating from coherent motion of the electron spins driven by the pulses. Experimental low-field DNP data are in very good agreement with this theoretical approach.

Monday, February 20, 2017

A combined EPR and MD simulation study of a nitroxyl spin label with restricted internal mobility sensitive to protein dynamics


Oganesyan, V.S., et al., A combined EPR and MD simulation study of a nitroxyl spin label with restricted internal mobility sensitive to protein dynamics. J. Magn. Reson., 2017. 274: p. 24-35.


EPR studies combined with fully atomistic Molecular Dynamics (MD) simulations and an MD-EPR simulation method provide evidence for intrinsic low rotameric mobility of a nitroxyl spin label, Rn, compared to the more widely employed label MTSL (R1). Both experimental and modelling results using two structurally different sites of attachment to Myoglobin show that the EPR spectra of Rn are more sensitive to the local protein environment than that of MTSL. This study reveals the potential of using the Rn spin label as a reporter of protein motions.

Friday, February 17, 2017

Using signal amplification by reversible exchange (SABRE) to hyperpolarise 119Sn and 29Si NMR nuclei


Olaru, A.M., et al., Using signal amplification by reversible exchange (SABRE) to hyperpolarise 119Sn and 29Si NMR nuclei. Chem Commun (Camb), 2016. 52(100): p. 14482-14485.


The hyperpolarisation of the 119Sn and 29Si nuclei in 5-(tributylstannyl)pyrimidine (ASn) and 5-(trimethylsilyl)pyrimidine (BSi) is achieved through their reaction with [IrCl(COD)(IMes)] (1a) or [IrCl(COD)(SIMes)] (1b) and parahydrogen via the SABRE process. 1a exhibits superior activity in both cases. The two inequivalent pyrimidine proton environments of ASn readily yielded signal enhancements totalling approximately 2300-fold in its 1H NMR spectrum at a field strength of 9.4 T, with the corresponding 119Sn signal being 700 times stronger than normal. In contrast, BSi produced analogous 1H signal gains of approximately 2400-fold and a 29Si signal that could be detected with a signal to noise ratio of 200 in a single scan. These sensitivity improvements allow NMR detection within seconds using micromole amounts of substrate and illustrate the analytical potential of this approach for high-sensitivity screening. Furthermore, after extended reaction times, a series of novel iridium trimers of general form [Ir(H)2Cl(NHC)(mu-pyrimidine-kappaN:kappaN')]3 precipitate from these solutions whose identity was confirmed crystallographically for BSi.

Wednesday, February 15, 2017

Hyperpolarized Nanodiamond Surfaces #DNPNMR


Rej, E., et al., Hyperpolarized Nanodiamond Surfaces. J Am Chem Soc, 2017. 139(1): p. 193-199.


The widespread use of nanodiamond as a biomedical platform for drug-delivery, imaging, and subcellular tracking applications stems from its nontoxicity and unique quantum mechanical properties. Here, we extend this functionality to the domain of magnetic resonance, by demonstrating that the intrinsic electron spins on the nanodiamond surface can be used to hyperpolarize adsorbed liquid compounds at low fields and room temperature. By combining relaxation measurements with hyperpolarization, spins on the surface of the nanodiamond can be distinguished from those in the bulk liquid. These results are likely of use in signaling the controlled release of pharmaceutical payloads.

Tuesday, February 14, 2017

[NMR] Multiple postdoc positions in Hyperpolarized 13C MR

From the Ampere Magnetic Resonance List


Multiple Postdoctoral Research Fellowship Positions in Hyperpolarized 13C Metabolic Imaging

The University of Maryland School of Medicine has expanded its molecular imaging and interventional research capabilities by establishing the Center for Metabolic Imaging and Therapeutics. The center houses a GE SpinLabTM dynamic nuclear polarizer suitable for preclinical and clinical applications, a GE 3T 750w MR scanner, and an MR Solutions MRS 3017 Preclinical Benchtop MR scanner. The GE MR scanner is also integrated with two Insightec 1024-element high-intensity focused ultrasound (HIFU) systems for image-guided interventions. Our goal is to facilitate both basic science and clinical research by exploring novel molecular imaging agent-based technologies for screening, early disease detection and treatment response, and real-time image-guided interventions.

Multiple postdoctoral research fellowship positions are available in the metabolic imaging group led by Dr. Dirk Mayer. Specific areas of research include optimized acquisition and reconstruction techniques, kinetic modeling for quantitative analysis, and new probe development. These methods will be applied to animal models (e.g., traumatic brain injury, cancer, liver disease) with translation to patients scheduled for summer 2017. This is an exciting opportunity to work at one of the first sites that will do translational/clinical hyperpolarized 13C MRI/MRS.

The candidate should have a Ph.D. (or equivalent degree) in engineering, physics, physical chemistry, or similar fields. The ideal candidate has a strong background in NMR physics with particular emphasis on in vivo imaging and/or spectroscopy, data acquisition and signal/image processing/analysis. Experience in pulse sequence programming (ideally on GE and/or MR Solutions scanners), knowledge of computer languages, such as C++, Matlab and IDL, and experience in performing small animal imaging is also desirable. Qualified applicants should also have a track record of peer-reviewed publications.

Interested individuals should send a letter detailing their research interests, an updated CV and contact information for at least two references to Dirk Mayer, Ph.D. (dmayer@som.umaryland.edu).

--
Dirk Mayer, Dr. rer. nat.
Associate Professor
Diagnostic Radiology & Nuclear Medicine
University of Maryland School of Medicine

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