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Anomalously high aggregation level of the polyene antibiotic amphotericin B in acidic medium: implications for the

Mariusz Gagoś1, Monika Hereć, Marta Arczewska

  • 1Department of Biophysics, Institute of Physics, Maria Curie-Skłodowska University, 20-031 Lublin, Poland.

Biophysical Chemistry
|May 13, 2008
PubMed

Insights

Amphotericin B (AmB) aggregation is pH-dependent. Low pH causes high aggregation, influencing its therapeutic and toxic effects in treating fungal infections.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Spectroscopy

Background:

  • Amphotericin B (AmB) is a crucial polyene antibiotic for deep fungal infections.
  • Drug efficacy and toxicity are linked to its molecular organization.
  • AmB exists as a zwitterion at neutral pH.

Purpose of the Study:

  • To investigate the pH-dependent molecular organization and aggregation of Amphotericin B.
  • To understand how pH influences AmB's aggregation state and pharmacological action.

Main Methods:

  • Spectroscopic analyses including electronic absorption, fluorescence, and infrared absorption.
  • Resonance light scattering techniques were employed.
  • Evaluation of AmB behavior across a range of pH values (acidic, neutral, alkaline).

Main Results:

  • At pH > 10, AmB exists as monomers due to its negative net charge.
  • At pH < 2, anomalously high aggregation occurs despite a positive net charge.
  • Low pH-induced aggregation is attributed to polyene chain polarization and mycosamine fragment mobility.

Conclusions:

  • Amphotericin B's aggregation state is significantly influenced by pH.
  • Understanding pH-dependent aggregation is critical for optimizing AmB's therapeutic and toxicological profiles.
  • This study provides insights into the molecular mechanisms underlying AmB's pharmacological action.

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