Temperature effects on the aggregation state and activity of amphotericin B

Biochim Biophys Acta. 1993 Oct 10;1152(1):185-8. doi: 10.1016/0005-2736(93)90246-v.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / chemistry*
  • Amphotericin B / toxicity
  • Arylsulfonates
  • Cell Membrane / chemistry*
  • Cell Membrane / drug effects
  • Cholesterol / chemistry
  • Circular Dichroism
  • Ergosterol / chemistry
  • Hydrogen-Ion Concentration
  • Lipid Bilayers / chemistry*
  • Liposomes / chemistry
  • Models, Biological
  • Potassium / chemistry
  • Temperature*

Substances

  • Arylsulfonates
  • Lipid Bilayers
  • Liposomes
  • Amphotericin B
  • Cholesterol
  • pyranine
  • Potassium
  • Ergosterol