Amphotericin B-sterol complex formation and competition with egg phosphatidylcholine: a monolayer study

Saint-Pierre-Chazalet, M.; Thomas, Christopher A.; Dupeyrat, M.; Gary-Bobo, C.M.

doi:10.1016/0005-2736(88)90519-6

Cited by 77 publications

(62 citation statements)

References 15 publications

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“…The mean area per DMPC molecule in a liquidcrystalline bilayer was experimentally determined [44] to be ~61.0 Å 2 . The average crosssectional area per AmB, as estimated in a monomolecular layer [45], is similar to the DMPC area and equals ~56.0 Å 2 . Since both studied derivatives have the cross-section very close to that of AmB [46], we set the area of the xy plane, A, to be 6084 Å 2 (78 × 78 Å) in all three of the studied systems.…”

Section: Accepted M Manuscriptmentioning

confidence: 67%

Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives — A molecular dynamics study

Neumann

Borowski

Bagiński

2009

Biophysical Chemistry

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. Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives -a molecular dynamics study. Biophysical Chemistry, Elsevier, 2009, 141 (1) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Author to whom the correspondence should be addressed. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT3 AbstractAmphotericin B (AmB) is an effective but very toxic antifungal antibiotic. In our laboratory a series of AmB derivatives of improved selectivity of action was synthesized and tested. To understand molecular basis of this improvement, comparative conformational studies of amphotericin B and its two more selective derivatives were carried out in an aqueous solution and in a lipid membrane. These molecular simulation studies revealed that within a membrane environment the conformational behavior of the derivatives differs significantly from the one observed for the parent molecule. Possible reasons for such a difference are analyzed. Furthermore, we hypothesize that the observed conformational transition within the polar head of AmB derivatives may lead to destabilization of antibioticinduced transmembrane channels. Consequently, the selective toxicity of the derivatives should increase as ergosterol-rich liquid-ordered domains are more rigid and conformationally ordered than their cholesterol-containing counterparts, and as such may better support less stable channel structure.

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Section: Accepted M Manuscriptmentioning

confidence: 67%

Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives — A molecular dynamics study

Neumann

Borowski

Bagiński

2009

Biophysical Chemistry

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“…Very efficient formation of dimeric structures by AmB has been predicted on the basis of the theoretical analysis of molecular interactions [17] and has been demonstrated with application of electronic absorption and fluorescence spectroscopic analyses [13,[18][19][20]. The formation of AmB dimers has been also concluded on the basis of monomolecular layer studies [21]. In the present work we address the problem of molecular organization of AmB using electronic absorption spectroscopy with non-polarized and polarized light and monomolecular layer technique.…”

Section: Accepted Manuscriptmentioning

confidence: 93%

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

Gagoś¹,

Gruszecki²

2008

Biophysical Chemistry

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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.

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“…In contrast, for mixtures with X AmB = 0.5 and 0.7, the overall desorption process is controlled by two steps (dissolution and diffusion), reaching eventually a steady state. This accounts for the existence of an interaction between AmB and cholesterol and indicates the presence of a stable complex, the formation of which has already been predicted from the excess free energy of mixing values (4,7). Comparing the mixtures of X AmB = 0.5 and 0.7 at the same surface pressure (15 mN/m) it is to be pointed out that although the rate of dissolution for both cases is practically the same, the values for θ * are different (90 min for X AmB = 0.7, and 75 min for X AmB = 0.5), indicating that for the mixture containing a 0.7 molar fraction of AmB, the steady state is attained after a longer period of time than for the 1 : 1 mixture.…”

Section: Resultsmentioning

confidence: 59%

“…To get further insight into AmB's mechanism of action, we have been researching the surface behavior of AmB alone as well as its interaction with sterols in monolayers at the air/water interface (4)(5)(6). The pressure/area (π/A) isotherm of AmB exhibits a characteristic transition plateau which separates two regions of liquid-expanded and liquid-condensed states (7,8). The 1 To whom correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

“…plateau was interpreted as due to reorientational changes in AmB molecules upon compression, from a horizontal to a vertical position (7,8). Successive compression-expansion experiments (8) have proved that the monolayer in the preplateau region is very stable as in the expanded state amphotericin molecules are lying flat on the surface, linked to surface water molecules by hydrogen bonds.…”

Section: Introductionmentioning

confidence: 99%

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Desorption of Amphotericin B from Mixed Monolayers with Cholesterol at the Air/Water Interface

Rey-Gómez-Serranillos

Dynarowicz-Łątka

Miñones

et al. 2001

Journal of Colloid and Interface Science

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Amphotericin B-sterol complex formation and competition with egg phosphatidylcholine: a monolayer study

Cited by 77 publications

References 15 publications

Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives — A molecular dynamics study

Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives — A molecular dynamics study

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

Desorption of Amphotericin B from Mixed Monolayers with Cholesterol at the Air/Water Interface

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