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Self-Association of Amphotericin B: Spontaneous Formation of Molecular Structures Responsible for the Toxic Side Effects of the Antibiotic
Abstract
Amphotericin B (AmB) is a lifesaving antibiotic used to treat deep-seated mycotic infections. Both the pharmaceutical activity and highly toxic side effects of the drug rely on its interaction with biomembranes, which is governed by the molecular organization of AmB. In the present work we present detailed analysis of self-assembly of AmB molecules in different environments, interesting from the physiological standpoint, based on molecular spectroscopy techniques: electronic absorption, circular dichroism, steady state and time-resolved fluorescence and molecular dynamic calculations. The results show that in the water medium, AmB self-associates to dimeric structures, referred to as "parallel" and "antiparallel". AmB dimers can further assembly into tetramers which can play a role of transmembrane ion channels, affecting electrophysiological homeostasis of a living cell. Understanding structural determinants of self-assembly of AmB opens a way to engineering preparations of the drug which retain pharmaceutical effectiveness under reduced toxicity.
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Authors (9)
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Joanna Starzyk
- Maria Curie-Skłodowska University Department of Biophysics, Institute of Physics
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Marcin Gruszecki
- Medical University of Gdansk Department of Informatics and Statistics
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Krzysztof Tutaj
- Maria Curie-Skłodowska University Department of Biophysics, Institute of Physics
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Rafal Luchowski
- Maria Curie-Skłodowska University Department of Biophysics, Institute of Physics
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Radosław Szlazak
- Maria Curie-Skłodowska University Department of Biophysics, Institute of Physics
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Piotr Waśko
- Maria Curie-Skłodowska University Department of Biophysics, Institute of Physics
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Wojciech Grudziński
- Maria Curie-Skłodowska University Department of Biophysics, Institute of Physics
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Wiesław I. Gruszecki
- Maria Curie-Skłodowska University Department of Biophysics, Institute of Physics
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Details
- Category:
- Articles
- Type:
- artykuł w czasopiśmie wyróżnionym w JCR
- Published in:
-
JOURNAL OF PHYSICAL CHEMISTRY B
no. 118,
edition 48,
pages 13821 - 13832,
ISSN: 1520-6106 - Language:
- English
- Publication year:
- 2014
- Bibliographic description:
- Starzyk J., Gruszecki M., Tutaj K., Luchowski R., Szlazak R., Waśko P., Grudziński W., Czub J., Gruszecki W.: Self-Association of Amphotericin B: Spontaneous Formation of Molecular Structures Responsible for the Toxic Side Effects of the Antibiotic// JOURNAL OF PHYSICAL CHEMISTRY B. -Vol. 118, iss. 48 (2014), s.13821-13832
- DOI:
- Digital Object Identifier (open in new tab) 10.1021/jp510245n
- Verified by:
- Gdańsk University of Technology
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