Amphotericin B Dimers with Bisamide Linkage Bearing Powerful Membrane-Permeabilizing Activity

Abstract

[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.