Organization of antibiotic amphotericin B in model lipid membranes. A mini review

• Autorzy: Gruszecki W I , Gagos M. , Herec M. , Kernen P.
• Języki publikacji: EN

Abstrakty

EN

Amphotericin B (AmB) is a polyene antibiotic frequently applied in the treatment of fungal infections. According to the general understanding, the mode of action of AmB is directly related to the molecular organization of the drug in the lipid environment, in particular to the formation of pore-like molecular aggregates. Electronic absorption and fluorescence techniques were applied to investigate formation of molecular aggregates of AmB in the lipid environment of liposomes and monomolecular layers formed at the argon-water interface. It appears that AmB dimers, stabilized by van der Waals interactions, are present in the membrane environment along with the aggregates formed by a greater number of molecules. Linear dichroism measurements reveal that AmB is distributed between two fractions of molecules, differently oriented with respect to the bilayer. Molecules in one fraction remain parallel to the plane of the membrane and molecules in the other one are perpendicular. Scanning Force Microscopy imaging of the surface topography of the monolayers formed with AmB in the presence of lipids reveals formation of pore-like structures characterized by the external diameter close to 17 Å and the internal diameter close to 6 Å. All the findings are discussed in terms of importance of the molecular organization of AmB in the pharmacological action, as well as of the toxic side effects of the drug.

Słowa kluczowe

EN

molecular aggregate; lipid membrane; amphotericin B; treatment; antibiotic; fungal infection

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2003
• Tom: 08
• Numer: 1
• Opis fizyczny: p.161-170,fig.

Twórcy

autor

Gruszecki W I

• Maria Curie-Sklodowska University, 20-031 Lublin, Poland

autor

Gagos M.

autor

Herec M.

autor

Kernen P.

Bibliografia

• 1. De Kruijff, B. and Demel, R.A. Polyene antibiotic-sterol interaction in membranes of Acholeplasma Laidlawii cells and lecithin liposomes; III Molecular structure of the polyene antibiotic-cholesterol complex. Biochim. Biophys. Acta. 339 (1974) 57-70.
• 2.Bagiński, M., Resat, H. and McCammon, J.A. Molecular properties of amphotericin B membrane channel: a molecular dynamics simulation. Mol. Pharmacol. 52 (1997) 560-570.
• 3. Cotero, B.V., Rebolledo-Antunez, S. and Ortega-Blake, I. On the role of sterol in the formation of the amphotericin B channel. Biochim. Biophys. Acta 1375 (1998) 43-51.
• 4. Hartsel, S. and Bolard, J. Amphotericin B: new life for an old drug. TiPS 17 (1996) 445-449.
• 5 Wójtowicz, K., Gruszecki, W. I., Walicka, M. and Barwicz, J. Effect of amphotericin B on dipalmitoylphosphatidylcholine membranes: calorimetry, ultrasound absorption and monolayer technique studies. Biochim. Biophys. Acta 1373 (1998) 220-226.
• 6. Barwicz, J., Gruszecki, W.I. and Gruda I. Spontaneous Organization of Amphotericin B in Aqueous Medium. J. Colloid Interf. Sci. 158 (1993) 71-76.
• 7. Gagoś, M., Koper, R. and Gruszecki, W.I. Spectrophotometric analysis of organisation of dipalmitoylphosphatidylcholine bilayers containing the polyene antibiotic amphotericin B. Biochim. Biophys. Acta 1511 (2001) 90-98.
• 8. Gruszecki, W.I., Gagoś, M. and Kernen, P. Polyene Antibiotic Amphotericin B in Monomolecular Layers: Spectrophotometric and Scanning Force Microscopic Analysis. FEBS Lett. 524 (2002) 92-96.
• 9. Parkash, J., Robblee, J. H., Agnew, J., Gibbs, E., Collings, P., Pasternack, R. F. and de Paula, J. C. Depolarized Resonance Light Scattering by Porphyrin and Chlorophyll a Aggregates. Biophys. J. 74 (1998) 2089-2099.
• 10. Gruszecki, W.I., Gagoś, M. and Hereć, M. Dimers of polyene antibiotic amphotericin B detected by means of fluorescence spectroscopy: molecular organization in solution and in lipid membranes. J. Photochem. Photobiol. B: Biol. 69 (2003) 49-57.