Related ArticlesAverage orientation of a fluoroaromatic molecule in lipid bilayers from DFT-informed NMR measurements of 1H-19F dipolar couplings.
Phys Chem Chem Phys. 2018 Jun 19;:
Authors: Hughes E, Griffin JM, Coogan MP, Middleton DA
Abstract
Fluorine is often incorporated into the aromatic moieties of synthetic bioactive molecules such as pharmaceuticals and disease diagnostics in order to alter their physicochemical properties. Fluorine substitution may increase a molecule's lipophilicity, thereby enabling its diffusion across cell membranes to enhance bioavailability or to exert a direct physiological effect from within the lipid bilayer. Understanding the structure, dynamics and orientation of fluoroaromatic molecules in lipid bilayers can provide useful insight into the effect of fluorine on their mode of action, and their interactions with membrane-embedded targets or efflux proteins. Here we demonstrate that NMR measurements of 19F chemical shift anisotropy combined with 1H-19F dipolar coupling measurements together report on the average orientation of a lipophilic fluoroaromatic molecule, 4-(6-fluorobenzo[d]thiazol-2-yl)aniline (FBTA), rapidly rotating within a lipid bilayer. The 19F chemical shift tensor orientation in the molecular frame was calculated by density functional theory and corroborated by 1H-19F PISEMA NMR. It was then possible to analyse the line shapes of proton-coupled and proton-decoupled 19F spectra of FBTA in chain perdeuterated dimyristoylphosphatidylcholine (DMPC-d54) bilayers to restrict the average axis of molecular reorientation of FBTA in the bilayer to a limited range orientations. This approach, which exploits the high sensitivity and gyromagnetic ratios of 19F and 1H, will be useful for comparing the membrane properties of related bioactive fluoroaromatic compounds.
PMID: 29915824 [PubMed - as supplied by publisher]
[NMR paper] Dynamic Structure and Orientation of Melittin Bound to Acidic Lipid Bilayers, As Revealed by Solid-State NMR and Molecular Dynamics Simulation.
Dynamic Structure and Orientation of Melittin Bound to Acidic Lipid Bilayers, As Revealed by Solid-State NMR and Molecular Dynamics Simulation.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg Related Articles Dynamic Structure and Orientation of Melittin Bound to Acidic Lipid Bilayers, As Revealed by Solid-State NMR and Molecular Dynamics Simulation.
J Phys Chem B. 2017 03 02;121(8):1802-1811
Authors: Norisada K, Javkhlantugs N, Mishima D, Kawamura I, Saitô H, Ueda K, Naito A
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[NMR paper] Self-assembled Oligopeptide as a Versatile NMR Alignment Medium for the Measurements of Residual Dipolar Couplings in Methanol
Self-assembled Oligopeptide as a Versatile NMR Alignment Medium for the Measurements of Residual Dipolar Couplings in Methanol
Residual dipolar coupling (RDC) constitutes a powerful structural parameter for the determination of constitution, conformation and configuration of organic molecules. Here, we report the first liquid crystalline based orientating medium that is compatible with MeOH, thus enabling RDC acquisitions of a wide range of intermediate to polar organic molecules. The liquid crystals were produced by the self-assembled oligopeptide nanotubes (AAKLVFF), which are stable...
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[NMR paper] Orientation and Location of the Cyclotide Kalata B1 in Lipid Bilayers Revealed by Solid-State NMR.
Orientation and Location of the Cyclotide Kalata B1 in Lipid Bilayers Revealed by Solid-State NMR.
Related Articles Orientation and Location of the Cyclotide Kalata B1 in Lipid Bilayers Revealed by Solid-State NMR.
Biophys J. 2017 Feb 28;112(4):630-642
Authors: Grage SL, Sani MA, Cheneval O, Henriques ST, Schalck C, Heinzmann R, Mylne JS, Mykhailiuk PK, Afonin S, Komarov IV, Separovic F, Craik DJ, Ulrich AS
Abstract
Cyclotides are ultra-stable cyclic disulfide-rich peptides from plants. Their biophysical effects and medically...
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[NMR paper] CW dipolar broadening EPR spectroscopy and mechanically aligned bilayers used to measure distance and relative orientation between two TOAC spin labels on an antimicrobial peptide
CW dipolar broadening EPR spectroscopy and mechanically aligned bilayers used to measure distance and relative orientation between two TOAC spin labels on an antimicrobial peptide
Publication date: December 2014
Source:Journal of Magnetic Resonance, Volume 249</br>
Author(s): Indra D. Sahu , Eric J. Hustedt , Harishchandra Ghimire , Johnson J. Inbaraj , Robert M. McCarrick , Gary A. Lorigan</br>
An EPR membrane alignment technique was applied to measure distance and relative orientations between two spin labels on a protein oriented along the surface of the...
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Solid-State NMR Measurements of Asymmetric Dipolar Couplings Provide Insight into Protein Side-Chain Motion.
Solid-State NMR Measurements of Asymmetric Dipolar Couplings Provide Insight into Protein Side-Chain Motion.
Solid-State NMR Measurements of Asymmetric Dipolar Couplings Provide Insight into Protein Side-Chain Motion.
Angew Chem Int Ed Engl. 2011 Sep 16;
Authors: Schanda P, Huber M, Boisbouvier J, Meier BH, Ernst M
PMID: 21928443
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Solid-State NMR Measurements of Asymmetric Dipolar Couplings Provide Insight into Protein Side-Chain Motion.
Solid-State NMR Measurements of Asymmetric Dipolar Couplings Provide Insight into Protein Side-Chain Motion.
Solid-State NMR Measurements of Asymmetric Dipolar Couplings Provide Insight into Protein Side-Chain Motion.
Angew Chem Int Ed Engl. 2011 Sep 14;
Authors: Schanda P, Huber M, Boisbouvier J, Meier BH, Ernst M
PMID: 21915969
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[NMR paper] Solid-state NMR measurements of the kinetics of the interaction between phospholamban and Ca2+-ATPase in lipid bilayers.
Solid-state NMR measurements of the kinetics of the interaction between phospholamban and Ca2+-ATPase in lipid bilayers.
Related Articles Solid-state NMR measurements of the kinetics of the interaction between phospholamban and Ca2+-ATPase in lipid bilayers.
Mol Membr Biol. 2005 Jul-Aug;22(4):353-61
Authors: Hughes E, Middleton DA
Phospholamban (PLB) is a small transmembrane protein that regulates calcium transport across the sarcoplasmic reticulum (SR) of cardiac cells via a reversible inhibitory interaction with Ca2+-ATPase. In this work...
Average orientation of a fluoroaromatic molecule in lipid bilayers from DFT-informed NMR measurements of 1H-19F dipolar couplings.
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