Effect of antibiotic amphotericin B on structural and dynamic properties of lipid membranes formed with egg yolk phosphatidylcholine

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Amphotericin B (AmB) is a life-saving antibiotic, used to treat deep-seated mycotic infections. Both the therapeutic and toxic side effects of AmB are directly dependent on its molecular organization. Organization of AmB was studied in monocomponent monomolecular layers formed at the argon-water interface, by means of polarized and nonpolarized electronic absorption spectroscopy and analyzed in terms of the exciton splitting theory. The results provide direct indication that AmB forms spontaneously dimers that can be assembled into molecular structures characterized by homogeneous orientational distribution in the monolayer, interpreted as cylindrical pores. The structures are not stable at surface pressures higher than 20 mN/m and therefore dimers are concluded as abundant molecular organization forms of AmB in biomembranes. Possibility of stabilization of the cylindrical structures, at higher surface pressures, by other molecules, eg. sterols, is also discussed.

Section: Accepted Manuscriptmentioning

confidence: 99%

Organization of polyene antibiotic amphotericin B at the argon–water interface

Gagoś¹,

Gruszecki²

2008

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“…It has been also proposed that selectivity toward cells of fungi is based upon a difference of the radii of porous structures of AmB binding ergosterol and cholesterol [6,9]. On the other hand, very recent reports show that alternatively both the biological action of the drug as well as toxic side effects may be directly related to the effect of AmB on physical properties of the membranes [10][11][12][13]. The 1 H-NMR technique studies demonstrated that the polar headgroup region of the membranes, rather than the hydrophobic core, is a predominant site of binding of AmB from the water phase [12].…”

Section: Introductionmentioning

confidence: 99%

“…The 1 H-NMR technique studies demonstrated that the polar headgroup region of the membranes, rather than the hydrophobic core, is a predominant site of binding of AmB from the water phase [12]. Analysis of the effect of AmB on structural and dynamic properties of lipid membranes carried out with application of SANS (small angle neutron scattering), 1 H-NMR and FTIR techniques showed that AmB molecules, even bound to the lipid polar groups, influence motional freedom of acyl lipid chains [11][12][13]. This effect is particularly pronounced in the case of the lipid…”

Section: Introductionmentioning

confidence: 99%

Molecular organization of antifungal antibiotic amphotericin B in lipid monolayers studied by means of Fluorescence Lifetime Imaging Microscopy

Gruszecki

Luchowski

Gagoś

et al. 2009

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Amphotericin B (AmB) is a life-saving polyene antibiotic used to treat deep-seated mycotic infections. Both the mode of therapeutic action as well as toxic side effects are directly dependent on molecular organization of the drug. Binding of AmB to lipid monolayers formed with dipalmitoylphosphatidylcholine, pure and containing 40 mol% cholesterol or ergosterol, the sterols of human and fungi respectively, has been examined by means of

“…In the latter case, AmB is postulated to self-aggregate into the hydrophilic pores that may severely affect transmembrane ion transport [8][9][10]. On the other hand, the results of the recent structural studies show that the pharmacological effect of AmB towards the membranes may be associated with modification of structural and dynamic properties of the lipid bilayer [11][12][13][14]. Despite the exact mode of action of AmB it is without doubt that both the pharmacological activity and the toxic side effects are strongly dependent on molecular organization of the drug in formulation [1,[15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Anomalously high aggregation level of the polyene antibiotic amphotericin B in acidic medium: Implications for the biological action

Gagoś

Hereć²,

Arczewska³

et al. 2008

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Amphotericin B (AmB) is a polyene antibiotic used to treat deep-seated mycoses. Both the therapeutic action and the toxic side effects of this drug are dependent on its molecular organization. AmB appears as a zwitterion at neutral pH owing to -NH 3 + and -COO -groups.The results obtained with electronic absorption, fluorescence, resonance light scattering and infrared absorption spectroscopic analyses show that in the aqueous medium at pH above 10 AmB appears in the monomeric form owing to the negative net electric charge of the molecule. On the contrary, anomalously high aggregation level has been observed at pH below 2, despite the positive net electric charge. The effect is interpreted in terms of the permanent polarization of the polyene chain at low pH, associated with relative rotational freedom of the charged mycosamine fragment of the molecule. The pH-dependent aggregation of AmB is discussed in aspect of pharmacological action of the drug.