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Ducker E.B.,Max Planck Institute for Biophysical Chemistry | Kuhn L.T.,EXC 171 | Kuhn L.T.,European Neuroscience Institute Gottingen ENI G | Munnemann K.,Max Planck Institute for Polymer Research | And 2 more authors.
Journal of Magnetic Resonance | Year: 2012

The Non-Hydrogenative Parahydrogen-Induced Polarization (NH-PHIP) technique, which is referred to as Signal Amplification by Reversible Exchange (SABRE), has been reported to be applicable to various substrates and catalysts. For more detailed studies, pyridine was mainly examined in the past. Here, we examined several pyrazole derivatives towards their amenability to this method using Crabtree's Catalyst, which is the polarization transfer catalyst that is best documented. Additionally, the dependence of the signal enhancement on the field strength, at which the polarization step takes place, was examined for pyridine and four different pyrazoles. To achieve this, the polarization step was performed at numerous previously determined magnetic fields in the stray field of the NMR spectrometer. The substrate dependence of the field dependence proved to be relatively small for the different pyrazoles and a strong correlation to the field dependence for pyridine was observed. Reducing the number of spins in the catalyst by deuteration leads to increased enhancement. This indicates that more work has to be invested in order to be able to reproduce the SABRE field dependence by simulations. © 2011 Elsevier Inc. All rights reserved.

Perez-Trujillo M.,Autonomous University of Barcelona | Castanar L.,Autonomous University of Barcelona | Monteagudo E.,Autonomous University of Barcelona | Kuhn L.T.,European Neuroscience Institute Gottingen ENI G | And 4 more authors.
Chemical Communications | Year: 2014

NMR enantiodifferentiation studies are greatly improved by the simultaneous determination of 1H and 13C chemical shift differences through the analysis of highly resolved cross-peaks in spectral aliased pure shift (SAPS) HSQC spectra. This journal is © the Partner Organisations 2014.

Perez-Trujillo M.,Autonomous University of Barcelona | Parella T.,Autonomous University of Barcelona | Kuhn L.T.,European Neuroscience Institute Gottingen ENI G
Analytica Chimica Acta | Year: 2015

NMR-aided enantiodiscrimination using chiral auxiliaries (CAs) is a recognized method for differentiating enantiomers and for measuring enantiomeric ratios (er). Up to the present, the study, optimization, and comparison of such methods have been performed based on the enantiodifferentiation of NMR signals via analyzing non-equivalent chemical-shift values (ΔΔδ) of the diastereoisomeric species formed. However, a poor and non-reliable comparison of results is often obtained via the analysis of ΔΔδ exclusively. In here, the concept of enantioresolution of an individual NMR signal and its importance for NMR-aided enantiodifferentiation studies is introduced and discussed. In addition, the enantioresolution quotient, E, is proposed as the parameter to describe its quantification. Complementary to measuring ΔΔδ, the experimental determination of E allows a more reliable interpretation of the results and opens up new possibilities for the study of enantiodifferentiation data derived from novel NMR experiments, setup improvements or new CAs. Finally, the different relationships between signal enantiodifferentiation, signal enantioresolution, and other main experimental issues of enantiodifferentiation experiments are addressed. © 2015 Elsevier B.V..

Rogne P.,European Neuroscience Institute Gottingen ENI G | Rogne P.,Dfg Res Center Molecular Physiology Of The Brain Cmpb Exc 171 Microscopy At The Nanometer Range | Ozdowy P.,European Neuroscience Institute Gottingen ENI G | Ozdowy P.,Dfg Res Center Molecular Physiology Of The Brain Cmpb Exc 171 Microscopy At The Nanometer Range | And 5 more authors.
PLoS ONE | Year: 2012

Atomic-level analyses of non-native protein ensembles constitute an important aspect of protein folding studies to reach a more complete understanding of how proteins attain their native form exhibiting biological activity. Previously, formation of hydrophobic clusters in the 6 M urea-denatured state of an ultrafast folding mini-protein known as TC5b from both photo-CIDNP NOE transfer studies and FCS measurements was observed. Here, we elucidate the structural properties of this mini-protein denatured in 6 M urea performing 15N NMR relaxation studies together with a thorough NOE analysis. Even though our results demonstrate that no elements of secondary structure persist in the denatured state, the heterogeneous distribution of R2 rate constants together with observing pronounced heteronuclear NOEs along the peptide backbone reveals specific regions of urea-denatured TC5b exhibiting a high degree of structural rigidity more frequently observed for native proteins. The data are complemented with studies on two TC5b point mutants to verify the importance of hydrophobic interactions for fast folding. Our results corroborate earlier findings of a hydrophobic cluster present in urea-denatured TC5b comprising both native and non-native contacts underscoring their importance for ultra rapid folding. The data assist in finding ways of interpreting the effects of pre-existing native and/or non-native interactions on the ultrafast folding of proteins; a fact, which might have to be considered when defining the starting conditions for molecular dynamics simulation studies of protein folding. © 2012 Rogne et al.

Schmidt M.,Max Planck Institute for Biophysical Chemistry | Sun H.,Max Planck Institute for Biophysical Chemistry | Rogne P.,European Neuroscience Institute Gottingen ENI G | Rogne P.,Research Center Molecular Physiology of the Brain | And 5 more authors.
Journal of the American Chemical Society | Year: 2012

Even though the important antimalaria drug rac-erythro-mefloquine HCl has been on the market as Lariam for decades, the absolute configurations of its enantiomers have not been determined conclusively. This is needed, since the (-) enantiomer is believed to cause adverse side effects in malaria treatment resulting from binding to the adenosine receptor in the human brain. Since there are conflicting assignments based on enantioselective synthesis and anomalous X-ray diffraction, we determined the absolute configuration using a combination of NMR, optical rotatory dispersion (ORD), and circular dichroism (CD) spectroscopy together with density functional theory calculations. First, structural models of erythro-mefloquine HCl compatible with NMR-derived 3J HH scalar couplings, 15N chemical shifts, rotational Overhauser effects, and residual dipolar couplings were constructed. Second, we calculated ORD and CD spectra of the structural models and compared the calculated data with the experimental values. The experimental results for (-)-erythro-mefloquine HCl matched our calculated chiroptical data for the 11R,12S model. Accordingly, we conclude that the assignment of 11R,12S to (-)-erythro-mefloquine HCl is correct. © 2011 American Chemical Society.

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