Cyclosporin A (CsA) is a hydrophobic cyclic peptide produced by the fungus Tolypocladium inflatum and composed of 11 aminoacids.
It is well known for its high efficiency as an immunosuppressor for transplanted organs and antiinflammatory properties, however, it is also
active as antiparasitic (antimalarian) drug [1].
Antimalarian mechanism of CsA action lacks a detailed understanding at molecular level. Due to a high lipophilicity
of CsA, it is able to interact with lipids of cellular membranes but molecular targets of this drug are still unknown. To get a deeper
insight into the mode of anitmalarian activity of this drug, it is of utmost importance to examine its interactions with membrane components.
To reach this goal, the Langmuir monolayer technique [2], which serves as a very useful, easy to handle and controllable model of biomembranes [3],
can be employed. However, the requirement for using this technique is that the molecule of interest must be surface active and capable of stable
Langmuir monolayer formation. Therefore, the aim of this paper is to provide Langmuir monolayer characterization of cyclosporine A and examine
its interactions with cell membrane lipids, i.e. DPPC, POPC, sphingomyelin and cholesterol. Differences in interactions between CsA and basic
membrane lipids can be helpful in finding molecular targets for its antimalarian activity.
References:
[1] J. F. Borel, C. Feurer, H. U. Gubler, H. Stähelin, Agents and Actions, 6, 468 (1976)
[2] G.L. Gaines Jr., Insoluble Monolayers at Liquid-Gas Interfaces (Interscience Publishers, New York, 1966)
[3] H. Brockman, Current Opinion in Structural Biology, 9, 438 (1999).
