The effects of amphotericin B on pure and ergosterol- or cholesterol-containing dipalmitoylphosphatidylcholine bilayers as viewed by 2H NMR.pdfVIP

Chemistry and Physics of Lipids 119 (2002) 1/ 11 /locate/chemphyslip The effects of amphotericin B on pure and ergosterol- or cholesterol-containing dipalmitoylphosphatidylcholine bilayers as viewed by 2H NMR a b b b Marie-Jose′e Paquet , Isabelle Fournier , Joanna Barwicz , Pierre Tancre`de , Miche`le Auger a,* a De′partement de Chimie, Centre de Recherche en Sciences et Inge′nierie des Macromole′cules, Universite′ Laval, Que′bec, QC, Canada G1K 7P4 b De′partement de Chimie-Biologie, Universite′ du Que′bec a` Trois-Rivie`res, B.P. 500, Trois-Rivie`res, QC, Canada G9A 5H7 Received 10 September 2001; received in revised form 8 November 2001; accepted 8 November 2001 Abstract Amphotericin B (AmB) is a widely used polyene antibiotic to treat systemic fungal infections. This drug is known to be lethal to fungal cells but it has also side effect toxicity on mammalian cells. The mechanism of action of AmB is thought to be related to the difference of the main sterol present in the mammalian and the fungal cells, namely cholesterol and ergosterol, respectively. The effect of AmB has been investigated on pure dipalmitoylphosphatidylcho- line (DPPC) and on cholesterol- and ergosterol-containing DPPC bilayers by 2H NMR spectroscopy. The 2H NMR results first confirm that AmB forms a complex with sterol-free DPPC bilayers, the interaction causing the structurization of the lipids and the inc