High-Resolution Magic Angle Spinning—Enabling Applications of NMR Spectroscopy to Semi-Solid Phases

Power, William P.

doi:10.1016/b978-0-12-385857-3.00003-7

Cited by 31 publications

(19 citation statements)

References 327 publications

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“…In a previous study, we introduced high-resolution magic angle spinning (HR-MAS) NMR spectroscopy as a suitable tool to study the metabolome of G. lamblia [26]. HR-MAS yields well-resolved liquid-like 1 H-NMR spectra from semi-solid materials, reducing resonance line broadening effects caused by dipolar interactions and magnetic susceptibility differences inherent to most semi-solid materials [27]. Therefore, HR-MAS NMR has become a very attractive tool in the analysis of small metabolites from biological materials such as cells and tissue samples [28,29] or food samples [30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Profiling of Wildtype and Transgenic Giardia lamblia Strains by 1H HR-MAS NMR Spectroscopy

et al. 2020

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Giardia lamblia, a causative agent of persistent diarrhea in humans, domestic animals, and cattle, is usually treated with nitro compounds. Consequently, enzymes involved in anaerobic nitro reduction have been investigated in detail as potential targets. Their role within the normal metabolic context is, however, not understood. Using 1H high-resolution magic angle spinning (HR-MAS) NMR spectroscopy, we analyzed the metabolomes of G. lamblia trophozoites overexpressing three nitroreductases (NR1–NR3) and thioredoxin reductase (TrxR), most likely a scavenger of reactive oxygen species, as suggested by the results published in this study. We compared the patterns to convenient controls and to the situation in the nitro drug resistant strain C4 where NR1 is downregulated. We identified 27 metabolites in G. lamblia trophozoites. Excluding metabolites of high variability among different wildtype populations, only trophozoites overexpressing NR1 presented a distinct pattern of nine metabolites, in particular arginine catabolites, differing from the respective controls. This pattern matched a differential pattern between wildtype and strain C4. This suggests that NR1 interferes with arginine and thus energy metabolism. The exact metabolic function of NR1 (and the other nitroreductases) remains to be elucidated.

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Section: Introductionmentioning

confidence: 99%

Metabolomic Profiling of Wildtype and Transgenic Giardia lamblia Strains by 1H HR-MAS NMR Spectroscopy

et al. 2020

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“…It combines the advantages of sensitive high-resolution NMR probes with magic angle spinning technology for suppression of dipolar couplings known from solid-state NMR. It has successfully been applied to a wide range of inhomogeneous samples like gels, swollen polymers, resins, foodstuff, cells, and tissue samples (Power, 2011). However, the applicability for quantification of low molecular weight compounds in feces remains to be tested.…”

Section: Downloaded Frommentioning

confidence: 99%

Comparison of¹⁹F NMR and¹⁴C Measurements for the Assessment of ADME of BYL719 (Alpelisib) in Humans

et al. 2017

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The human mass balance study is the definitive study for the assessment of absorption, distribution, metabolism, and excretion (ADME) properties of a new chemical entity in humans. Traditionally this has been carried out by the administration of radiolabeled drug substances, typically C or occasionallyH, as detection methods for these isotopes allow the absolute quantification of drug-related material (DRM) in blood, plasma, and excreta. Coupled with the use of analytical techniques such as liquid chromatography-mass spectrometry, a picture of the metabolic fate of a compound can be elucidated. In this study, we demonstrate the capabilities of F nuclear magnetic resonance (NMR) spectroscopy, applied as an alternative to radiolabeling, for the determination of mass balance and for metabolite profiling of an orally administered fluorinated drug. To demonstrate the capabilities of NMR, the study was conducted on remaining samples from aC human mass balance study conducted on Alpelisib (BYL719), a compound in late stage development at Novartis for the treatment of solid tumors. Quantitative C data were used to cross-validate the data obtained by NMR. The data show that, usingF NMR, comparable data can be obtained for key human ADME endpoints including mass balance, total DRM determination in plasma and metabolite profiling and identification in plasma and excreta. Potential scenarios where NMR could be employed as an alternative to radiolabeling for the conduct of an early human ADME study are discussed.

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“…To acquire a high-resolution spectrum of a semi-solid, High Resolution Magic Angle Spinning (HR-MAS) was developed in the late 1990's as a hybrid between solid and solution state NMR. [118] Similar to solid state NMR the spinning of the sample at the "magic angle" (54.7°) to the applied magnetic field reduces line broadening effects. Spinning speeds are typically between 3 to 5 kHz and cells remain intact and viable.…”

Section: Semi-solid State and Macromolecular Assembliesmentioning

confidence: 99%

“…HR-MAS does not require the high powered pulses that solid state NMR requires and many of the nD experiments that are utilized for structural biology can be applied, although stable iso-tope labelling is preferred for the less abundant 13 C, and 15 N nuclei. HR-MAS can be applied for many natural product studies [118,120] commonly used to study metabolic changes in diseased and treated tissues, [121,122] metabolism, [123] combinatorial chemistry [124] and whole cells [125]. Intensities in the HR-MAS NMR spectra are dependent on the environment of the analyte and as such molecules that are in rigid environments with completely restricted mobility are not detected.…”

Section: Semi-solid State and Macromolecular Assembliesmentioning

confidence: 99%

Magnetic Resonance Technologies: Molecules to Medicine

Merkley¹,

Burton²,

Karakach³

et al. 2013

Using Old Solutions to New Problems - Natural Drug Discovery in the 21st Century

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High-Resolution Magic Angle Spinning—Enabling Applications of NMR Spectroscopy to Semi-Solid Phases

Cited by 31 publications

References 327 publications

Metabolomic Profiling of Wildtype and Transgenic Giardia lamblia Strains by 1H HR-MAS NMR Spectroscopy

Metabolomic Profiling of Wildtype and Transgenic Giardia lamblia Strains by 1H HR-MAS NMR Spectroscopy

Comparison of¹⁹F NMR and¹⁴C Measurements for the Assessment of ADME of BYL719 (Alpelisib) in Humans

Magnetic Resonance Technologies: Molecules to Medicine

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High-Resolution Magic Angle Spinning—Enabling Applications of NMR Spectroscopy to Semi-Solid Phases

Cited by 31 publications

References 327 publications

Metabolomic Profiling of Wildtype and Transgenic Giardia lamblia Strains by 1H HR-MAS NMR Spectroscopy

Metabolomic Profiling of Wildtype and Transgenic Giardia lamblia Strains by 1H HR-MAS NMR Spectroscopy

Comparison of19F NMR and14C Measurements for the Assessment of ADME of BYL719 (Alpelisib) in Humans

Magnetic Resonance Technologies: Molecules to Medicine

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Comparison of¹⁹F NMR and¹⁴C Measurements for the Assessment of ADME of BYL719 (Alpelisib) in Humans