Magnetically Aligned Bicelles To Study the Orientation of Lipophilic Ligands in Membrane Bilayers

Guo, Zhixiong; Yang, De‐Ping; Chari, Ravi; Tian, Xiaoyu; Pavlopoulos, Spiro; Lu, Dai; Makriyannis, Alexandros

doi:10.1021/jm800766x

Cited by 5 publications

(7 citation statements)

References 36 publications

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“…No such NOEs were observed for Me-Δ 8 -THC congruent with the notion that the long axis of this more lipophilic analog is aligned with lipid molecules so that the side chain group extends away from the ring system [18,19]. Anisotropic measurements further proved that Δ 8 -THC and Me-Δ 8 -THC are oriented perpendicular and parallel, respectively, in the bicelle environment consistent with their observed conformations.…”

Section: Introductionsupporting

confidence: 64%

“…4). In an earlier publication involving the conformational analysis of CP55940, all three hydroxyl groups of CP55940 were found to orient toward the upper face of the molecule that allows for a preferred orientation within the membrane [5,9,15,18,19]. This orientation favors a close interaction between both the cyclohexane and phenolic rings of CP55940 with the phospholipid membrane interface (Fig.…”

Section: Discussionmentioning

confidence: 99%

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The interaction of cannabinoid receptor agonists, CP55940 and WIN55212-2 with membranes using solid state 2H NMR

Tian

Pavlopoulos

Yang

et al. 2011

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Two key commonly used cannabinergic agonists, CP55940 and WIN55212-2, are investigated for their effects on the lipid membrane bilayer using 2H solid state NMR, and the results are compared with our earlier work with delta-9-tetrahydrocannabinol (Δ9-THC). To study the effects of these ligands we used hydrated bilayers of dipalmitoylphosphatidylcholine (DPPC) deuterated at the 2′ and 16′ positions of both acyl chains with deuterium atoms serving as probes for the dynamic and phase changes at the membrane interface and at the bilayer center respectively. All three cannabinergic ligands lower the phospholipid membrane phase transition temperature, increase the lipid sn-2 chain order parameter at the membrane interface and decrease the order at the center of the bilayer. Our studies show that the cannabinoid ligands induce lateral phase separation in the lipid membrane at physiological temperatures. During the lipid membrane phase transition, the cooperative dynamic process whereby the C-2H segments at the interface and center of the bilayer spontaneously reach the fast exchange regime (2H NMR timescale) is distinctively modulated by the two cannabinoids. Specifically, CP55940 is slightly more efficient at inducing liquid crystalline-type 2H NMR spectral features at the membrane interface compared to WIN55212-2. In contrast, WIN55212-2 has a far superior ability to induce liquid crystalline-type spectral features at the center of the bilayer, and it increases the order parameter of the sn-1 chain in addition to the sn-2 chain of the lipids. These observations suggest the cannabinoid ligands may influence lipid membrane domain formations and there may be contributions to their cannabinergic activities through lipid membrane microdomain related mechanisms. Our work demonstrates that experimental design strategies utilizing specifically deuterium labeled lipids yield more detailed insights concerning the properties of lipid bilayers.

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Section: Introductionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

The interaction of cannabinoid receptor agonists, CP55940 and WIN55212-2 with membranes using solid state 2H NMR

Tian

Pavlopoulos

Yang

et al. 2011

Biochimica et Biophysica Acta (BBA) - Biomembranes

Self Cite

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“…Structural and dynamic properties of stearic acid- d 35 in bicelles containing cholesterol have been studied by 2 H NMR [220] and later compared to EPR results [221]. Two cannabinoids were investigated in the presence of oriented bicelles [222]. In this study, two deuterium labeled sites yielded orientational constraints from spectra obtained on a solution-state NMR spectrometer, and were analyzed in terms of structure and dynamics.…”

Section: Interaction Of Small Molecules With Bicellesmentioning

confidence: 99%

When detergent meets bilayer: Birth and coming of age of lipid bicelles

Dürr

Soong

Ramamoorthy

2013

Progress in Nuclear Magnetic Resonance Spectroscopy

119

108

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“…Molecules possessing a phenolic hydroxyl group are localized in the interface of the lipid bilayers, with the phenolic hydroxyl group probably hydrogen-bonding either with the head-group or the glycerol carbonyls. The methylated analogs locate themselves deeper in the hydrophobic region since they lack the anchor for the polar region (Guo et al 2008;Martel et al 1993;Mavromoustakos et al 1991;1995a, b;1996a, b;1999;Sarpietro et al 2007, Yang et al 1993.…”

Section: Introductionmentioning

confidence: 99%

Comparison of thermal effects of stilbenoid analogs in lipid bilayers using differential scanning calorimetry and molecular dynamics: correlation of thermal effects and topographical position with antioxidant activity

et al. 2011

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In previous studies it was shown that cannabinoids (CBs) bearing a phenolic hydroxyl group modify the thermal properties of lipid bilayers more significantly than methylated congeners. These distinct differential properties were attributed to the fact that phenolic hydroxyl groups constitute an anchoring group in the vicinity of the headgroup, while the methylated analogs are embedded deeper towards the hydrophobic region of the lipid bilayers. In this work the thermal effects of synthetic polyphenolic stilbenoid analogs and their methylated congeners have been studied using differential scanning calorimetry (DSC).Molecular dynamics (MD) simulations have been performed to explain the DSC results. Thus, two of their phenolic hydroxyl groups orient in the lipid bilayers in such a way that they anchor in the region of the headgroup. In contrast, their methoxy congeners cannot anchor effectively and are embedded deeper in the hydrophobic segment of the lipid bilayers. The MD results explain the fact that hydroxystilbenoid analogs exert more significant effects on the pretransition than their methoxy congeners, especially at low concentrations. To maximize the polar interactions, the two phenolic hydroxyl groups are localized in the vicinity of the head-group region, directing the remaining hydroxy group in the hydrophobic region. This topographical position of stilbenoid analogs forms a mismatch that explains the significant broadening of the width of the phase transition and lowering of the main phasetransition temperature in the lipid bilayers. At high concentrations, hydroxy and nonhydroxy analogs appear to form different domains. The correlation of thermal effects with antioxidant activity is discussed.

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Magnetically Aligned Bicelles To Study the Orientation of Lipophilic Ligands in Membrane Bilayers

Cited by 5 publications

References 36 publications

The interaction of cannabinoid receptor agonists, CP55940 and WIN55212-2 with membranes using solid state 2H NMR

The interaction of cannabinoid receptor agonists, CP55940 and WIN55212-2 with membranes using solid state 2H NMR

When detergent meets bilayer: Birth and coming of age of lipid bicelles

Comparison of thermal effects of stilbenoid analogs in lipid bilayers using differential scanning calorimetry and molecular dynamics: correlation of thermal effects and topographical position with antioxidant activity

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