Interaction of cyclosporin A with dipalmitoylphosphatidylcholine

Timothy S. Wiedmann, Theodore Trouard, S. C. Shekar, Maria Polikandritou, Yueh Erh Rahman

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Cyclosporin A, a hydrophobic cyclic peptide, is a potent immunosuppressant. In an attempt to determine the localization of cyclosporin A in phospholipid membranes, the effect of cyclosporin A on dipalmitoylphosphatidylcholine (DPPC) has been investigated using deuterium nuclear magnetic resonance (2H-NMR) spectroscopy and differential scanning calorimetry (DSC). Cyclosporin A was dispersed within acyl chain per-deuterated DPPC at a concentration of 6 mole percent, hydrated with buffer, and the spectra obtained over a range of temperatures were compared with that of pure DPPC. The changes caused by cyclosporin A were assessed by the first moment (M1) and order parameters calculated from the spectra. The presence of cyclosporin A decreases the magnitude of M1 at temperatures below the gel to liquid-crystalline state, cyclosporin A causes an increase in the order parameters along the acyl chains which suggests that cyclosporin A is located along the acyl chains of the phospholipid. For DSC, cyclosporin A was dispersed in non-deuterated DPPC at different peptide to phospholipid mole ratios. The endothermic peaks associated with the gel to liquid-cystalline phase transition and pretransition were recorded and compared with similar mole ratios of cholesterol to lipid. At 30 mole percent cyclosporin A, small decreases in the main transition temperature and associated enthalpy were observed, whereas at 30 mole percent cholesterol, the main transition is barely distinguishable from the baseline. The pretransition was not observed with the addition of 11 mole percent of either cyclosporin A or cholesterol. The results of the thermal analysis indicate that although cyclosporin A and cholesterol appear to be both located along the acyl chains of the phospholipids, they have dramatically different interactions with the membrane lipids.

Original languageEnglish (US)
Pages (from-to)12-18
Number of pages7
JournalBBA - Biomembranes
Volume1023
Issue number1
DOIs
StatePublished - Mar 30 1990

Keywords

  • Cholesterol
  • Cyclosporin A
  • Dipalmitoylphosphatidylcholine
  • Lipid-protein interaction
  • NMR, H-

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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    Wiedmann, T. S., Trouard, T., Shekar, S. C., Polikandritou, M., & Rahman, Y. E. (1990). Interaction of cyclosporin A with dipalmitoylphosphatidylcholine. BBA - Biomembranes, 1023(1), 12-18. https://doi.org/10.1016/0005-2736(90)90003-7