Solid state 2H-NMR as a method for determining the orientation of cannabinoid analogs in membranes

Yang, De‐Ping; Banijamali, A.; Charalambous, Avgui; Marciniak, Gilbert; Makriyannis, Alexandros

doi:10.1016/0091-3057(91)90362-6

Cited by 19 publications

(43 citation statements)

References 8 publications

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“…Using solid-state [ 2 H]-NMR spectroscopy, these investigators have found that the amphipathic D 9 -THC (3) uses its phenolic hydroxyl to anchor itself at the interface of the amphipathic membrane bilayer, while it orients the long axis of its tricyclic system perpendicular to the bilayer; smallangle X-ray results confirmed this interpretation (Makriyannis et al, 1989). Cannabinoids with two hydroxyl groups orient in a manner that allows both hydroxyls to be near the interface facing the polar surface of the membrane (Yang et al, 1991). However, if the phenolic hydroxyl of D 9 -THC is replaced with a methoxy group, the cannabinoid orients with its natural axis parallel to the lipid acyl chains (Yang et al, 1992).…”

Section: Biophysical Studies Of Cannabinoids In a Lipid Environmentmentioning

confidence: 68%

Lipids, lipid rafts and caveolae: Their importance for GPCR signaling and their centrality to the endocannabinoid system

2005

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Section: Biophysical Studies Of Cannabinoids In a Lipid Environmentmentioning

confidence: 68%

Lipids, lipid rafts and caveolae: Their importance for GPCR signaling and their centrality to the endocannabinoid system

2005

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“…The orientation of cannabinoid ligands in bilayers was previously investigated for the cannabis ingredients D 9 -THC (25,26), D 8 -THC (26)(27)(28), and a functionally inactive analog, O-methyl-D 8 -THC (Me-D 8 -THC) (26,28,29). Small-angle x-ray diffraction at ~6 A ˚resolution and 2 H NMR quadrupolar splittings of the isotope-labeled tricyclic rings showed that D 9 -THC and D 8 -THC are located near the water-membrane interface and oriented with the bond connecting the hydroxyphenyl and cyclohexenyl rings perpendicular to the bilayer normal (25)(26)(27)(28). With this orientation, the hydroxyl group at the phenyl ring is exposed to the water phase.…”

Section: Introductionmentioning

confidence: 99%

“…With this orientation, the hydroxyl group at the phenyl ring is exposed to the water phase. In contrast, Me-D 8 -THC, a methylated analog at the hydroxyl group, has an orientation of the same bond parallel to the bilayer normal (26,28,29). It was suggested that the orientation of the functionally active D 9 -THC and D 8 -THC may be critical for ensuring efficient access to the receptor-binding pocket from the lipid matrix (26).…”

Section: Introductionmentioning

confidence: 99%

Location, Structure, and Dynamics of the Synthetic Cannabinoid Ligand CP-55,940 in Lipid Bilayers

Kimura

Cheng

Rice

et al. 2009

Biophysical Journal

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The widely used hydrophobic cannabinoid ligand CP-55,940 partitions with high efficiency into biomembranes. We studied the location, orientation, and dynamics of CP-55,940 in POPC bilayers by solid-state NMR. Chemical-shift perturbation of POPC protons from the aromatic ring-current effect, as well as 1H NMR cross-relaxation rates, locate the hydroxyphenyl ring of the ligand near the lipid glycerol, carbonyls, and upper acyl-chain methylenes. Order parameters of the hydroxyphenyl ring determined by the 1H-13C DIPSHIFT experiment indicate that the bond between the hydroxyphenyl and hydroxycyclohexyl rings is oriented perpendicular to the bilayer normal. 2H NMR order parameters of the nonyl tail are very low, indicating that the hydrophobic chain maintains a high level of conformational flexibility in the membrane. Lateral diffusion rates of CP-55,940 and POPC were measured by 1H magic-angle spinning NMR with pulsed magnetic field gradients. The rate of CP-55,940 diffusion is comparable to the rate of lipid diffusion. The magnitude of cross-relaxation and diffusion rates suggests that associations between CP-55,940 and lipids are with lifetimes of a fraction of a microsecond. With its flexible hydrophobic tail, CP-55,940 may efficiently approach the binding site of the cannabinoid receptor from the lipid-water interface by lateral diffusion.

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“…For this purpose, we incorporated the expanded set of all six 2 H quadrupolar splitting values into our calculations and removed the constraint of uniaxial symmetry (31, 32). The theory behind the matrix method rests on the concept that the order parameter S is actually a second-order tensor, represented by a 3×3 matrix.…”

Section: Resultsmentioning

confidence: 99%

17β-estradiol (E2) in membranes: Orientation and dynamic properties

Guo

Yang

Tian

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Non-genomic membrane effects of estrogens are of great interest because of the diverse biological activities they may elicit. To further our understanding of the molecular features of the interaction between estrogenic hormones and membrane bilayers, we have determined the preferred orientation, location and dynamic properties of 17β-estradiol (E2) in two different phospholipid membrane environments using 2H- NMR and 2D 1H-13C HSQC in conjunction with molecular dynamics simulations. Unequivocal spectral assignments to specific 2H labels were made possible by synthesizing six selectively deuterated E2 molecules. The data allow us to conclude that the E2 molecule adopts a nearly “horizontal” orientation in the membrane bilayer with its long axis essentially perpendicular to the lipid acyl chains. All four rings of the E2 molecule are located near the membrane interface, allowing both the E2 3-OH and the 17β-OH groups to engage in hydrogen bonding and electrostatic interactions with polar phospholipid groups. The findings augment our knowledge of the molecular interactions between E2 and membrane bilayer and highlight the asymmetric nature of the dynamic motions of the rigid E2 molecule in a membrane environment.

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Solid state 2H-NMR as a method for determining the orientation of cannabinoid analogs in membranes

Cited by 19 publications

References 8 publications

Lipids, lipid rafts and caveolae: Their importance for GPCR signaling and their centrality to the endocannabinoid system

Lipids, lipid rafts and caveolae: Their importance for GPCR signaling and their centrality to the endocannabinoid system

Location, Structure, and Dynamics of the Synthetic Cannabinoid Ligand CP-55,940 in Lipid Bilayers

17β-estradiol (E2) in membranes: Orientation and dynamic properties

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