Lipid-amphotericin B complex structure in solution: a possible first step in the aggregation process in cell membranes.

A R Balakrishnan; K R Easwaran

doi:10.1021/bi00066a040

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Lipid-amphotericin B complex structure in solution: a possible first step in the aggregation process in cell membranes.

A R Balakrishnan·K R Easwaran

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Abstract

The interactions between the polyene antibiotic amphotericin B with dipalmitoylphosphatidylcholine were investigated in vesicles (using circular dichroism) and in chloroform solution (using circular dichroism and 1H, 13C, and 31P nuclear magnetic resonance). The results show that amphotericin B readily aggregates in vesicles and that the extent of aggregation depends on the lipid:drug concentration ratio. Introduction of sterol molecules into the membrane hastens the process of aggregation of amphotericin B. In chloroform solutions amphotericin B strongly interacts with phospholipid molecules to form a stoichiometric complex. The results suggest that there are interactions between the conjugated heptene stretch of amphotericin B and the methylene groups of lipid acyl chains, while the sugar moiety interacts with the phosphate head group by the formation of a hydrogen bond. A model is proposed for the lipid-amphotericin B complex, in which amphotericin B interacts equally well with the two lipid acyl chains, forming a 1:1 complex.

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1,2-Dipalmitoylphosphatidylcholine Amphotericin B Cell Membrane Cholesterol Circular Dichroism Ergosterol Magnetic Resonance Spectroscopy Membrane Lipids Membrane Proteins Models, Biological Molecular Conformation Protein Conformation Solutions Journal Article Research Support, Non-U.S. Gov't

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A R Balakrishnan, K R Easwaran. 1993-04-20. Lipid-amphotericin B complex structure in solution: a possible first step in the aggregation process in cell membranes.. https://doi.org/10.1021/bi00066a040

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