Lipid-amphotericin B complex structure in solution: a possible first step in the aggregation process in cell membranes.
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.
Balakrishnan
A R
AR
Molecular Biophysics Unit, Indian Institute of Science, Bangalore.
Easwaran
K R
KR
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000666:Amphotericin B / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol; D002942:Circular Dichroism; D004875:Ergosterol; D009682:Magnetic Resonance Spectroscopy; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D008968:Molecular Conformation; D011487:Protein Conformation; D012996:Solutions
D008563:Membrane Lipids; D008565:Membrane Proteins; D012996:Solutions; D015060:1,2-Dipalmitoylphosphatidylcholine; D000666:Amphotericin B; D002784:Cholesterol; D004875:Ergosterol