Amphipathic interactions of cannabinoids with membranes. A comparison between Δ8-THC and its O-methyl analog using differential scanning calorimetry, X-ray diffraction and solid state 2H-NMR

Yang, De‐Ping; Mavromoustakos, Thomas; Beshah, Kebede; Makriyannis, Alexandros

doi:10.1016/0005-2736(92)90053-o

Cited by 43 publications

(35 citation statements)

References 26 publications

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“…Furthermore, since MD analysis has been performed for both CB1 and CB2 receptors, results can be useful for synthetic chemists to produce more selective CB compounds. The localization of AMG3 at the binding sites of the CB1 and CB2 receptors are in the core region of TM3-TM7 in accordance with reported biophysical crystallographic and modelling studies [102][103][104][105][106][107][108][109][110][111][112][113][114][115] (Fig. 3).…”

Section: Strategy Applied For a System-iisupporting

confidence: 89%

Strategies in the Rational Drug Design

Mavromoustakos

Durdağı²,

Koukoulitsa³

et al. 2011

CMC

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Rational design is applied in the discovery of novel lead drugs. Its rapid development is mainly attributed to the tremendous advancements in the computer science, statistics, molecular biology, biophysics, biochemistry, medicinal chemistry, pharmacokinetics and pharmacodynamics experienced in the last few decades. The promising feature that characterizes the application of rational drug design is that it uses for developing potential leads in drug discovery all known theoretical and experimental knowledge of the system under study. The utilization of the knowledge of the molecular basis of the system ultimately aims to reduce human power cost, time saving and laboratory expenses in the drug discovery. In this review paper various strategies applied for systems which include: (i) absence of knowledge of the receptor active site; (ii) the knowledge of a homology model of a receptor, (iii) the knowledge of the experimentally determined (i.e. X-ray crystallography, NMR spectroscopy) coordinates of the active site of the protein in absence and (iv) the presence of the ligand will be analyzed.

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Section: Strategy Applied For a System-iisupporting

confidence: 89%

Strategies in the Rational Drug Design

Mavromoustakos

Durdağı²,

Koukoulitsa³

et al. 2011

CMC

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“…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: 99%

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

2005

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“…In the past, we have published a series of papers in which the role of phenolic hydroxyl group of cannabinoids (CBs) has been studied (Mavromoustakos et al 1991;1995a, b;1996a, b;Yang et al 1992). It is well known that phenolic hydroxyl groups in the CB family play a pivotal role in their bioactivity.…”

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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Amphipathic interactions of cannabinoids with membranes. A comparison between Δ8-THC and its O-methyl analog using differential scanning calorimetry, X-ray diffraction and solid state 2H-NMR

Cited by 43 publications

References 26 publications

Strategies in the Rational Drug Design

Strategies in the Rational Drug Design

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

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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