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Keywords = NOESY MAS spectra

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15 pages, 4462 KB  
Article
Conformational State of Fenamates at the Membrane Interface: A MAS NOESY Study
by Ilya A. Khodov, Konstantin V. Belov, Daniel Huster and Holger A. Scheidt
Membranes 2023, 13(6), 607; https://doi.org/10.3390/membranes13060607 - 17 Jun 2023
Cited by 14 | Viewed by 10961
Abstract
The present work analyzes the 1H NOESY MAS NMR spectra of three fenamates (mefenamic, tolfenamic, and flufenamic acids) localized in the lipid–water interface of phosphatidyloleoylphosphatidylcholine (POPC) membranes. The observed cross-peaks in the two-dimensional NMR spectra characterized intramolecular proximities between the hydrogen atoms [...] Read more.
The present work analyzes the 1H NOESY MAS NMR spectra of three fenamates (mefenamic, tolfenamic, and flufenamic acids) localized in the lipid–water interface of phosphatidyloleoylphosphatidylcholine (POPC) membranes. The observed cross-peaks in the two-dimensional NMR spectra characterized intramolecular proximities between the hydrogen atoms of the fenamates as well as intermolecular interactions between the fenamates and POPC molecules. The peak amplitude normalization for an improved cross-relaxation (PANIC) approach, the isolated spin-pair approximation (ISPA) model, and the two-position exchange model were used to calculate the interproton distances indicative of specific conformations of the fenamates. The results showed that the proportions of the A+C and B+D conformer groups of mefenamic and tolfenamic acids in the presence of POPC were comparable within the experimental error and amounted to 47.8%/52.2% and 47.7%/52.3%, respectively. In contrast, these proportions for the flufenamic acid conformers differed and amounted to 56.6%/43.4%. This allowed us to conclude that when they bind to the POPC model lipid membrane, fenamate molecules change their conformational equilibria. Full article
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12 pages, 2175 KB  
Article
Membrane Interaction of Ibuprofen with Cholesterol-Containing Lipid Membranes
by Jan Kremkow, Meike Luck, Daniel Huster, Peter Müller and Holger A. Scheidt
Biomolecules 2020, 10(10), 1384; https://doi.org/10.3390/biom10101384 - 28 Sep 2020
Cited by 33 | Viewed by 4810
Abstract
Deciphering the membrane interaction of drug molecules is important for improving drug delivery, cellular uptake, and the understanding of side effects of a given drug molecule. For the anti-inflammatory drug ibuprofen, several studies reported contradictory results regarding the impact of ibuprofen on cholesterol-containing [...] Read more.
Deciphering the membrane interaction of drug molecules is important for improving drug delivery, cellular uptake, and the understanding of side effects of a given drug molecule. For the anti-inflammatory drug ibuprofen, several studies reported contradictory results regarding the impact of ibuprofen on cholesterol-containing lipid membranes. Here, we investigated membrane localization and orientation as well as the influence of ibuprofen on membrane properties in POPC/cholesterol bilayers using solid-state NMR spectroscopy and other biophysical assays. The presence of ibuprofen disturbs the molecular order of phospholipids as shown by alterations of the 2H and 31P-NMR spectra of the lipids, but does not lead to an increased membrane permeability or changes of the phase state of the bilayer. 1H MAS NOESY NMR results demonstrate that ibuprofen adopts a mean position in the upper chain/glycerol region of the POPC membrane, oriented with its polar carbonyl group towards the aqueous phase. This membrane position is only marginally altered in the presence of cholesterol. A previously reported result that ibuprofen is expelled from the membrane interface in cholesterol-containing DMPC bilayers could not be confirmed. Full article
(This article belongs to the Section Molecular Structure and Dynamics)
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