title: Channels formed by amphotericin B covalent dimers exhibit rectification.
abstract: Amphotericin B (AmB) is a widely used antifungal antibiotic with high specificity for fungi. We previously synthesized several covalently conjugated AmB dimers to clarify the AmB channel structure. Among these dimers, that with an aminoalkyl linker was found to exhibit potent hemolytic activity. We continue this work by investigating the channel activity of the dimer, finding that all channels comprised of AmB dimers show rectification. The direction of the dimer channel in the membrane depended on the electric potential at which the dimer channel was formed. On the other hand, only about half the monomer channels showed rectification. In addition, these channels were easily switched from a rectified to a nonrectified state following voltage stimulation, indicating instability. We propose a model to describe the AmB channel structure that explains why AmB dimer channels necessarily show rectification.
authors.affiliation: Laboratory for Cell Dynamics Observation, Planning Office for the Center for Computational and Quantitative Life Science, RIKEN, 7th Floor, Nanobiology Building, 1-3, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Hirano
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Matsumori
authors.forename: Michio
authors.initials: M
authors.lastname: Murata
authors.forename: Toru
authors.initials: T
authors.lastname: Ide
mesh_terms: D000666:Amphotericin B / Q000737:chemistry* / Q000378:metabolism*; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D019281:Dimerization; D015394:Molecular Structure
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B