title: Possible conformation of amphotericin B dimer in membrane-bound assembly as deduced from solid-state NMR.
abstract: Aiming for structural analysis of amphotericin B (AmB) ion-channel assemblies in membrane, a covalent dimer was synthesized between (13)C-labled AmB methyl ester and (19)F-labled AmB. The dimer showed slightly weaker but significant biological activities against fungi and red blood cells compared with those of monomeric AmB. Then the dimer was subjected to (13)C{(19)F}REDOR (Rotational-Echo Double Resonance) experiments in hydrated lipid bilayers. The obtained REDOR dephasing effects were explained by two components; a short (13)C/(19)F distance (6.9Å) accounting for 23% of the REDOR dephasing, and a longer one (14Å) comprising the rest of the dephasing. The shorter distance is likely to reflect the formation of barrel-stave ion channel.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Umegawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Adachi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Matsumori
authors.forename: Michio
authors.initials: M
authors.lastname: Murata
mesh_terms: D000666:Amphotericin B / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy; D001234:Aspergillus niger / Q000187:drug effects*; D019281:Dimerization; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation
chemical_list: D000935:Antifungal Agents; D008051:Lipid Bilayers; D000666:Amphotericin B