title: Anomalously high aggregation level of the polyene antibiotic amphotericin B in acidic medium: implications for the biological action.
abstract: Amphotericin B (AmB) is a polyene antibiotic used to treat deep-seated mycoses. Both the therapeutic action and the toxic side effects of this drug are dependent on its molecular organization. AmB appears as a zwitterion at neutral pH owing to NH(3)(+) and COO(-) groups. The results obtained with electronic absorption, fluorescence, resonance light scattering and infrared absorption spectroscopic analyses show that in the aqueous medium at pH above 10 AmB appears in the monomeric form owing to the negative net electric charge of the molecule. On the contrary, anomalously high aggregation level has been observed at pH below 2, despite the positive net electric charge. The effect is interpreted in terms of the permanent polarization of the polyene chain at low pH, associated with relative rotational freedom of the charged mycosamine fragment of the molecule. The pH-dependent aggregation of AmB is discussed in aspect of pharmacological action of the drug.
authors.affiliation: Department of Biophysics, Institute of Physics, Maria Curie-Skłodowska University, 20-031 Lublin, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Gagoś
authors.forename: Monika
authors.initials: M
authors.lastname: Hereć
authors.forename: Marta
authors.initials: M
authors.lastname: Arczewska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Czernel
authors.forename: Mauro
authors.initials: M
authors.lastname: Dalla Serra
authors.forename: Wiesław I
authors.initials: WI
authors.lastname: Gruszecki
mesh_terms: D000143:Acids / Q000737:chemistry*; D000666:Amphotericin B / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D000143:Acids; D000935:Antifungal Agents; D000666:Amphotericin B