Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives - A molecular dynamics study.
Biophys Chem
; 141(1): 105-16, 2009 Apr.
Article
en En
| MEDLINE
| ID: mdl-19185412
ABSTRACT
Amphotericin 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 antibiotic-induced 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Modelos Moleculares
/
Anfotericina B
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Membrana Dobles de Lípidos
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Antibacterianos
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Conformación Molecular
Idioma:
En
Revista:
Biophys Chem
Año:
2009
Tipo del documento:
Article
País de afiliación:
Polonia