title: Direct interaction between amphotericin B and ergosterol in lipid bilayers as revealed by 2H NMR spectroscopy.
abstract: Although amphotericin B (AmB) is thought to exert its antifungal activity by forming transmembrane ion-permeable self-assemblies together with ergosterol, no previous study has directly proven AmB-ergosterol interaction. To establish the interaction, we measured (2)H NMR using deuterium-labeled sterols and AmB. The (2)H NMR spectra of deuterated ergosterol in palmitoyloleoylphosphatidylcholine (POPC) bilayers showed that fast axial diffusion of erogosterol was almost completely inhibited by the coexistence of AmB. Conversely, cholesterol mobility in POPC membrane was essentially unchanged with or without AmB. These results unequivocally demonstrate that ergosterol has significant interaction with AmB in POPC bilayers. In addition, we examined the mobility of AmB using deuterium-labeled AmB, and found that, although AmB is almost immobilized in sterol-free and cholesterol-containing POPC membranes, a certain ratio of AmB molecules acquires mobility in the presence of ergosterol. The similar mobility of AmB and ergosterol in POPC bilayers confirmed the idea of the direct intermolecular interaction between ergosterol and AmB.
authors: Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan. matsmori@chem.sci.osaka-u.ac.jp
authors: Nobuaki
authors: N
authors: Matsumori
authors: Kazuaki
authors: K
authors: Tahara
authors: Hiroko
authors: H
authors: Yamamoto
authors: Atsushi
authors: A
authors: Morooka
authors: Mototsugu
authors: M
authors: Doi
authors: Tohru
authors: T
authors: Oishi
authors: Michio
authors: M
authors: Murata
mesh_terms: D000666:Amphotericin B / Q000378:metabolism* / Q000494:pharmacology; D000935:Antifungal Agents / Q000378:metabolism* / Q000494:pharmacology; D004875:Ergosterol / Q000378:metabolism*; D007553:Isotope Labeling; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009068:Movement / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D008051:Lipid Bilayers; D010743:Phospholipids; D000666:Amphotericin B; D004875:Ergosterol