Magnetically aligned bicelles to study the orientation of lipophilic ligands in membrane bilayers.
Magnetically aligned bicelles were used as a model membrane to study the orientation and dynamic properties of two cannabinoids (Delta (8)-THC and Me-Delta (8)-THC) using (31)P and (2)H NMR. The uniform alignment of the bicelles allowed us to obtain well resolved deuterium spectra from a solution NMR spectrometer. The preferred orientations of Delta (8)-THC and Me-Delta (8)-THC were calculated on the basis of the measurements of individual quadrupolar splittings. Our results agree with previous experiments using multilamellar membranes as well as with molecular dynamics simulation data described here. In conjunction with our earlier report using small and fast tumbling bicelles, the present work of well aligned bicelles shows that bicelle preparations can provide either pseudoisotropic or anisotropic NMR spectra to study the conformation, orientation, and dynamic properties of ligands in membrane bilayers. Such data are of critical value for understanding the interactions of lipophilic drug molecules with membrane proteins.
Center for Drug Discovery, 116 Mugar Life Sciences Building, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.
Jianxin
J
Guo
De-Ping
DP
Yang
Ravi
R
Chari
Xiaoyu
X
Tian
Spiro
S
Pavlopoulos
Dai
D
Lu
Alexandros
A
Makriyannis
D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D008958:Models, Molecular; D015394:Molecular Structure
D008024:Ligands; D008051:Lipid Bilayers