title: Head-to-tail interaction between amphotericin B and ergosterol occurs in hydrated phospholipid membrane.
abstract: Amphotericin B (AmB) is thought to exert its antifungal activity by forming an ion-channel assembly in the presence of ergosterol. In the present study we aimed to elucidate the mode of molecular interactions between AmB and ergosterol in hydrated phospholipid bilayers using the rotational echo double resonance (REDOR) spectra. We first performed (13)C{(19)F}REDOR experiments with C14-(19)F-labeled AmB and biosynthetically (13)C-labeled ergosterol and implied that both "head-to-head" and "head-to-tail" orientations occur for AmB-ergosterol interaction in the bilayers. To further confirm the "head-to-tail" pairing, (13)C-labeled ergosterol at the dimethyl terminus (C26/C27) was synthesized and subjected to the REDOR measurements. The spectra unambiguously demonstrated the presence of a "head-to-tail" orientation for AmB-ergosterol pairing. In order to obtain information on the position of the dimethyl terminus of ergosterol in membrane, (13)C{(31)P}REDOR were carried out using the labeled ergosterol and the phosphorus atom of a POPC headgroup. Significant REDOR dephasing was observed at the C26/C27 signal of ergosterol in the presence of AmB, but not in the absence of AmB, clearly indicating that the side-chain terminus of ergosterol in the AmB complex comes close to the bilayer surface.
authors: Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
authors: Yuichi
authors: Y
authors: Umegawa
authors: Yasuo
authors: Y
authors: Nakagawa
authors: Kazuaki
authors: K
authors: Tahara
authors: Hiroshi
authors: H
authors: Tsuchikawa
authors: Nobuaki
authors: N
authors: Matsumori
authors: Tohru
authors: T
authors: Oishi
authors: Michio
authors: M
authors: Murata
mesh_terms: D000666:Amphotericin B / Q000737:chemistry*; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D002247:Carbon Isotopes; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D041961:Deuterium Exchange Measurement; D004875:Ergosterol / Q000096:biosynthesis / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D010759:Phosphorus Isotopes; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D002247:Carbon Isotopes; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010743:Phospholipids; D010759:Phosphorus Isotopes; D014867:Water; D000666:Amphotericin B; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; D004875:Ergosterol