title: Amphotericin B covalent dimers bearing a tartarate linkage.
abstract: Amphotericin B (AmB, 1) is known to assemble together and form an ion channel across biomembranes, by which the drug presumably exerts its antimicrobial activity. To access the whole architecture of this channel assemblage, the understanding of binary interaction between AmB molecules is of prime importance because the dimeric interaction is the basis of the assemblage. In this context, we have recently reported covalently conjugated AmB dimers such as 2 and 3 with a long linker, which show prominent hemolytic potency and ion-channel activity. To evaluate the effect of the length and hydrophilicity of linker parts on the activity, we prepared new dimers bearing tartarate linkages (4 and 5). Especially, 5 exhibited potent hemolytic activity (EC50, 0.03 microM) surpassing those of AmB, 2, and 3. Measurements of UV and CD spectra of 5 in liposomes indicated that AmB portions of 5 could adopt appropriate arrangements in molecular assemblage in spite of the short linkage, and also indicated that the assemblage formed by 5 appeared more stable than AmB. These short-tethered dimers are expected to be a promising tool to reveal the mechanism of dimeric interaction in the ion channel formed by AmB.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University, 1-16 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Matsumori
authors.forename: Rie
authors.initials: R
authors.lastname: Masuda
authors.forename: Michio
authors.initials: M
authors.lastname: Murata
mesh_terms: D000666:Amphotericin B / Q000737:chemistry* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry* / Q000494:pharmacology; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008567:Membranes, Artificial; D013644:Tartrates / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D003432:Cross-Linking Reagents; D008567:Membranes, Artificial; D013644:Tartrates; D000666:Amphotericin B; C029768:tartaric acid