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.