Amphotericin B dimers with bisamide linkage bearing powerful membrane-permeabilizing activity.
[structure: see text] Covalently linked dimers of amphotericin B were prepared by cross-linking its carboxylic acid. Among these, a dimer with a linkage of 1,6-hexanediamine revealed potent hemolytic activity (EC50, 0.25 microM) while its N-acetyl derivative gave rise to large K+ ion flux in phosphatidylcholine liposomes, regardless of the presence or absence of sterols, suggesting that the dimers may serve as a tool for elucidating the structure of the ion channel assemblage formed by amphotericin B.
Yamaji
Nahoko
N
Department of Chemistry, Graduate School of Science, Osaka University, 1-16 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
Matsumori
Nobuaki
N
Matsuoka
Shigeru
S
Oishi
Tohru
T
Murata
Michio
M
D000666:Amphotericin B / Q000737:chemistry* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002942:Circular Dichroism; D019281:Dimerization; D006461:Hemolysis; D009682:Magnetic Resonance Spectroscopy
D000666:Amphotericin B