Temperature effects on the aggregation state and activity of amphotericin B.
Amphotericin B (AmB) in aqueous solution becomes less aggregated as temperature is increased as measured by CD spectroscopy. Concomitantly, AmB's ability to induce K+ leakage from cholesterol-containing large unilamellar vesicles (LUV) decreases 4-fold per 10 degrees C increase. In contrast, ergosterol-containing vesicles show no clear trend in their temperature sensitivity to AmB action. These data strongly support a model of AmB action where drug aggregates and not monomers are the major channel-inducing species against cholesterol- but not ergosterol-containing membranes.
Chemistry Department, University of Wisconsin-Eau Claire 54702.
H E
HE
Lambing
B D
BD
Wolf
S C
SC
Hartsel
D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D001190:Arylsulfonates; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D002942:Circular Dichroism; D004875:Ergosterol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008954:Models, Biological; D011188:Potassium / Q000737:chemistry; D013696:Temperature
D001190:Arylsulfonates; D008051:Lipid Bilayers; D008081:Liposomes; D000666:Amphotericin B; D002784:Cholesterol; C005047:pyranine; D011188:Potassium; D004875:Ergosterol