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Binding of doxorubicin to cardiolipin as compared to other anionic phospholipids—An evaluation of electrostatic effects

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Bioscience Reports

Abstract

The binding of doxorubicin to large unilamellar vesicles consisting of cardiolipin or other anionic phospholipids was analyzed in terms of the local drug concentration at the membrane surface, according to the Gouy-Chapman theory. The analysis suggests strong positive binding cooperativity. Part of the drug binds in the uncharged form. The affinity for cardiolipin and other anionic phospholipids is comparable. A binding level of 0.5 doxorubicin per lipid-phosphorus is reached when the local concentration of free doxorubicin monomer-equivalents at the membrane surface is about 0.2–0.7 mM. This contrasts with earlier findings indicating a 300–1000 fold higher affinity for cardiolipin. The present analysis provides an explanation for this apparent discrepancy.

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Authors and Affiliations

  1. Institute of Molecular Biology and Medical Biotechnology and Centre for Biomembranes and Lipid Enzymology, State University of Utrecht, Padualaan 8, 3584 CH, Utrecht, The Netherlands

    Frits A. de Wolf

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  1. Frits A. de Wolf
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de Wolf, F.A. Binding of doxorubicin to cardiolipin as compared to other anionic phospholipids—An evaluation of electrostatic effects. Biosci Rep 11, 275–284 (1991). https://doi.org/10.1007/BF01127503

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  • DOI: https://doi.org/10.1007/BF01127503

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