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Interactions of cyclosporines with lipid membranes as studied by solid-state nuclear magnetic resonance spectroscopy and high-sensitivity titration calorimetry

Schote, U. and Ganz, P. and Fahr, A. and Seelig, J.. (2002) Interactions of cyclosporines with lipid membranes as studied by solid-state nuclear magnetic resonance spectroscopy and high-sensitivity titration calorimetry. Journal of pharmaceutical sciences, Vol. 91, H. 3. pp. 856-867.

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Official URL: http://edoc.unibas.ch/dok/A5257401

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Abstract

Cyclosporin A (CyA) interacts with lipid membranes. Binding reaction and membrane location of CyA and analogs were examined with 2H-NMR, high-sensitivity isothermal titration calorimetry (ITC), and CD spectroscopy. Effects of CyA and charged analogs on the phosphocholine head group and on the membrane interior were investigated using selectively deuterated phospholipids. Incorporation of cyclosporin generated small disordering of the lipid acyl chains. Binding of CyA and neutral and positively charged analogs to lipid membranes showed endothermic heats of reaction between + 5.9 and + 11.3 kcal/mol, whereas enthalpy of binding was close to zero for the negatively charged derivative. Binding constants of cyclosporines to liposomal membranes were in the range of K(P) = 1650-5560 M(- 1) depending on the cholesterol content. (2)H-NMR provides evidence that CyA is essentially located in the interior of the bilayer membrane. For the charged analogs an additional interaction occurs at the head group level, placing the polar groups of these CyA analogs in the vicinity of the phosphocholine dipoles. The association of CyA and its analogs is accompanied by a positive enthalpy change, which is overcompensated by positive entropy changes. Binding of CyA to lipid membranes thus follows the classical hydrophobic effect, which is in contrast to many other peptide-lipid binding reactions.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Biophysical Chemistry (Seelig J)
UniBasel Contributors:Seelig, Joachim
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Pharmaceutical Association
ISSN:0022-3549
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:19
Deposited On:22 Mar 2012 13:18

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