Polydispersity of aggregates formed by the polyene antibiotic amphotericin B and deoxycholate. A spin label study.
The amphotericin B-deoxycholate (AB-DOC) system (1:2, mole basis) was studied with regard to its organizational properties making use of spin label ESR spectra. The spectra of a fatty acid spin label intercalated in AB-DOC preparations revealed two components, one strongly (S) and one weakly (W) immobilized. Spectral subtractions indicated that S corresponds to label in mixed AB-DOC aggregates while W is due to label in deoxycholate micelles. This situation, coexistence of different aggregates, is similar to that found in systems consisting of bile salts and phospholipids. The DOC/AB mole ratio in the mixed aggregate is highest when pure DOC micelles are present. Dilution leads to disappearance of the latter and to continuous loss of DOC from AB-DOC accompanied by an increase in size and decrease in solubility of the aggregates, as verified by filtration and centrifugation experiments. The results indicate that AB-DOC systems are polydisperse. Since amphotericin B preparations having different organizational properties display different toxic and therapeutic effect, the study of amphotericin B aggregates should help in understanding these phenomena at a molecular level.
Lamy-Freund
M T
MT
Department of Biochemistry, Universidade de São Paulo, Brazil.
Ferreira
V F
VF
Schreier
S
S
D000666:Amphotericin B; D003840:Deoxycholic Acid; D004578:Electron Spin Resonance Spectroscopy; D008823:Micelles; D012995:Solubility; D013113:Spin Labels
D008823:Micelles; D013113:Spin Labels; D003840:Deoxycholic Acid; D000666:Amphotericin B