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Published May 22, 2008 | public
Journal Article

Fluorine-19 NMR Chemical Shift Probes Molecular Binding to Lipid Membranes


The binding of amphiphilic molecules to lipid bilayers is followed by ^(19)F NMR using chemical shift and line shape differences between the solution and membrane-tethered states of −CF_3 and −CHF_2 groups. A chemical shift separation of 1.6 ppm combined with a high natural abundance and high sensitivity of ^(19)F nuclei offers an advantage of using ^(19)F NMR spectroscopy as an efficient tool for rapid time-resolved screening of pharmaceuticals for membrane binding. We illustrate the approach with molecules containing both fluorinated tails and an acrylate moiety, resolving the signals of molecules in solution from those bound to synthetic imyristoylphosphatidylcholine bilayers both with and without magic angle sample spinning. The potential in vitro and in vivo biomedical applications are outlined. The presented method is applicable with the conventional NMR equipment, magnetic fields of several Tesla, stationary samples, and natural abundance isotopes.

Additional Information

© 2008 American Chemical Society. Received 23 January 2008. Published online 19 April 2008. Published in print 1 May 2008. We thankfully acknowledge funding from the Tobacco Related Disease Research Program New Investigator Grant 16KT-0044, NIH 1R21 CA118509, NIH R01 CA 122513, the Rudi Schulte Research Institute (RSRI) (B.D.R., E.Y.C.), the James G. Boswell Fellowship (E.Y.C.), the American Heart Association (P.B., S.K.C.), the American Brain Tumor Association (P.B.), the Beckman Institute Pilot Program: "Spin Polarized Molecules for Structural and Systems Biology" (D.P.W.), the Cancer Research and Prevention Foundation (E.Y.C.), and the SURF program at Caltech (D.T.). We thank Dr. Sonjong Hwang for providing convenient access to the 11.7 T Bruker Avance solid-state NMR facility at Caltech.

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