Investigation of the α-cyclodextrin-myo-inositol phosphate inclusion complex by NMR spectroscopy and molecular modeling

Crouzy, Serge; Fauvelle, F.; Debouzy, Jean‐Claude; Göschl, Mathias; Chapron, Yves

doi:10.1016/0008-6215(96)00058-4

Cited by 14 publications

(17 citation statements)

References 20 publications

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“…Moreover, a NMR study demonstrates that a CD interacts very strongly with phosphatidylinositol (PI), and only weakly with phosphatidylcholine (Fauvelle et al 1994). The direct implication of the inositol headgroup in the complexation mechanism is proposed for phospholipid recognition at the membrane level and is confirmed in our study of c~ CD-myo-inositol phosphate interaction (Crouzy et al 1996). The NMR results together with equivalent observations from other authors (Szejtli et al 1986) suggest that the nature of the lipid headgroup is one decisive factor in the ability of cyclodextrins to form complexes with phospholipids.…”

Section: Introductionsupporting

confidence: 65%

Molecular dynamics study of an ?-cyclodextrin-phosphatidylinositol inclusion complex

1996

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Cyclodextrins are cyclic oligosaccharides known for their ability to include substrate molecules in their hydrophobic cavity. Moreover, cyclodextrins show a hemolytic activity when mM concentrations are added to blood. This hemolysis is commonly interpreted as a massive dissociation of phospholipids from the cell membrane due to the formation of complexes with the cyclodextrins. In the literature, a complexation between alpha-cyclodextrin (alpha CD) and phosphatidylinositol (PI) specific to the inositol headgroup has been proposed. But the need for the detailed interaction mechanism between the two molecules motivated the present work based on molecular dynamics simulations. Investigation of long range electrostatic interactions shows that a mutual approach of the molecules is only possible when the primary hydroxyl side of alpha CD faces the inositol headgroup of PI. This orientation is also the most favourable from adiabatic-and free-energy profiles calculated along a reaction coordinate that leads to an inclusion of PI into alpha CD. For free energy simulations, partial hydration of the model has been used. A study of glycosidic bond dihedral angles in alpha CD shows an increase in dihedral fluctuations before complexation and a dihedral "freezing" once the complex is formed.

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Section: Introductionsupporting

confidence: 65%

Molecular dynamics study of an ?-cyclodextrin-phosphatidylinositol inclusion complex

1996

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“…In the case of PI, the high affinity of PI toward R-CD is related to the existence of a specific inositol-headgroup -R-CD interaction, and a stable association of both molecules in the bulk phase is managed via sn 2 alkyl chain inclusion. 24,33 Second, chain inclusion is the main interaction mechanism to form stable complexes with the other phospholipids (e.g., PS, PE, and PC). However, when chain inclusion is preceded by the extraction of the lipid from the membrane, the electrostatic properties of the lipid headgroup (charge and dipole-moment) are the main factors governing any closer approach between R-CD and the membrane surface.…”

Section: Discussionmentioning

confidence: 99%

“…Although the contribution of the isotropic line to the total spectrum is not significantly different between the two systems when in the same phase (i.e., DMPE at 320 K and PE at 300 K), typical line widths measured on the resolved isotropic line of the DMPE/RCD system are narrower (20 Hz) than those measured on the PE/RCD samples (30)(31)(32)(33)(34)(35). This result suggests that the associated species PE/ RCD and DMPE/RCD are different, either in their degree of aggregation or in their dynamic properties.…”

Section: Experimentssmentioning

confidence: 92%

“…33,34 High-resolution 1 H NMR experiments of the different headgroups in solution (phosphoserine, phosphoethanolamine (PHS), phosphocholine (PHE), and glycerophosphodiester derivatives] were recorded in the presence of R-CD. As shown in Figure 2 (PHC, right column), no significant differences were observed on either the 1 H NMR chemical shift or on the line width.…”

Section: Experimentssmentioning

confidence: 99%

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Mechanism of α-Cyclodextrin Induced Hemolysis. 2. A Study of the Factors Controlling the Association with Serine-, Ethanolamine-, and Choline-Phospholipids

Debouzy¹,

Fauvelle²,

Crouzy³

et al. 1998

Journal of Pharmaceutical Sciences

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A nuclear magnetic resonance (NMR) spectroscopy and molecular modeling study of the interaction between alpha-cyclodextrin (alpha-CD) and phospholipids with serine, ethanolamine, or choline headgroups is presented. The experimental approach is based on 31P and 1H NMR measurements on small unilamellar vesicles (SUV), multilamellar systems (MLV), and aqueous suspensions of lipids using a direct complex preparation with alpha-CD. Molecular dynamics computer simulations are used to investigate the trajectory of alpha-CD in the vicinity of a membrane surface and the influence of the charge and dipole moment of the phospholipid headgroups. These factors of charge and orientation of dipole moment seem to play a key role in the interaction of phospholipids with alpha-CD and reflect very well the experimentally observed selectivity of the phospholipid -alpha-CD approach. However, with this approach, there is no evidence for the formation of a complex with the phospholipid headgroup (except for phosphatidylinositol) that results from electrostatic forces. Rather, after a possible extraction of the lipid from the membrane, a classical inclusion of the sn-2 chain in the cavity of alpha-CD occurs. This step depends on the alkyl chain length and saturation state of the lipids as well as on their organization (i.e., as vesicles or dispersions). Based on our results, chemical modifications of the alpha-CD molecule to control the hemolytic properties of alpha-CD are discussed.

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“…[30][31][32][33] Figure 1 shows the 1 H NMR spectra of SMs formed at a concentration of 10 Â 10 À3 M. There was a downfield shift for all of the protons of the SMs prepared using various stirring times. The proton resonance increased gradually up to a stirring period of 36 h; this increase can be attributed to the de-shielding and shielding XRD is a widely used technique for the study of supramolecular aggregates to assess the aggregate structure and to monitor the formation of new compounds from parent molecules.…”

Section: Resultsmentioning

confidence: 97%

Cyclodextrin Supramacromolecules: Unexpected Formation in Aqueous Phase under Ambient Conditions

Rao

Geckeler

2011

Macromol. Rapid Commun.

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The unexpected formation of supramacromolecules of β-cyclodextrin in aqueous solution under ambient conditions is reported in this article. The shape and size of the supramacromolecules could be controlled by varying the stirring time and the concentration. The supramolecular interactions of the supramacromolecules were confirmed by ¹H NMR spectroscopy. Additionally, visual evidence of the supramacromolecules was provided by transmission and scanning electron microscopy. The thermal behavior of the supramacromolecules was examined by thermogravimetric analysis. The molecular mass determination by gel permeation chromatography showed that the supramacromolecules had a high molar mass.

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Investigation of the α-cyclodextrin-myo-inositol phosphate inclusion complex by NMR spectroscopy and molecular modeling

Cited by 14 publications

References 20 publications

Molecular dynamics study of an ?-cyclodextrin-phosphatidylinositol inclusion complex

Molecular dynamics study of an ?-cyclodextrin-phosphatidylinositol inclusion complex

Mechanism of α-Cyclodextrin Induced Hemolysis. 2. A Study of the Factors Controlling the Association with Serine-, Ethanolamine-, and Choline-Phospholipids

Cyclodextrin Supramacromolecules: Unexpected Formation in Aqueous Phase under Ambient Conditions

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