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Updated: Jan 25, 2026
Membrane-SPINE: A Biochemical Tool to Identify Protein-protein Interactions of Membrane Proteins In Vivo
Published on: November 7, 2013
Interactions of miltefosine with erythrocyte membrane proteins compared to those of ionic surfactants
Lais Alonso1, Éder Jéferson Souza Cardoso2, Sebastião Antônio Mendanha2
1Instituto de Física, Universidade Federal de Goiás, Goiânia, GO, Brazil; Departamento de Farmácia e Farmacologia, Universidade Estadual de Maringá, Maringá, PR, Brazil.
Abstract:
For miltefosine (MIL), a zwitterionic alkylphospholipid approved for leishmaniasis treatment, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy has indicated that the interaction of MIL with membrane proteins has similarities to that of ionic surfactants. A general concern about leishmanicides is their high hemolytic potential, so we decided to compare the interactions of MIL and three ionic surfactants with the erythrocyte membrane. Measurements with two different spin labels indicated that the surfactants sodium dodecyl sulfate (SDS, anionic), cetyltrimethylammonium chloride (CTAC, cationic) and N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS, zwitterionic) as well as MIL increase the dynamics of erythrocyte membrane proteins in a concentration-dependent manner. SDS produced the smallest increases in protein dynamics and was also the least hemolytic for measurements in PBS and in whole blood. Spin label EPR measurements performed directly in the blood plasma detected increased albumin stiffness caused by 2.5 mM SDS due to electrostatic/hydrophobic interactions. For 10 mM concentrations of the compounds, the EPR spectra showed a fraction of albumin with greater mobility and another with the same as that of the untreated plasma. The zwitterionic compounds MIL and HPS did not present significant differences in this study.
Insights
Miltefosine (MIL) and surfactants affect erythrocyte membrane protein dynamics. Zwitterionic compounds like MIL and HPS showed minimal hemolytic potential and less impact on albumin compared to ionic surfactants.
Area of Science:
- Biochemistry
- Membrane Biophysics
- Pharmacology
Background:
- Miltefosine (MIL) is an approved leishmaniasis treatment with an unclear mechanism of action.
- Concerns exist regarding the hemolytic potential of leishmanicides.
- MIL's interaction with membrane proteins resembles that of ionic surfactants.
Purpose of the Study:
- To compare the interactions of MIL with erythrocyte membranes against ionic surfactants.
- To evaluate the hemolytic potential of MIL and selected surfactants.
- To investigate the effects of these compounds on membrane protein dynamics and albumin structure.
Main Methods:
- Electron paramagnetic resonance (EPR) spectroscopy using two different spin labels.
- Hemolysis assays in phosphate-buffered saline (PBS) and whole blood.
- EPR measurements directly in blood plasma to assess albumin interactions.
Main Results:
- MIL, SDS, CTAC, and HPS increased erythrocyte membrane protein dynamics concentration-dependently.
- Sodium dodecyl sulfate (SDS) showed the least hemolysis and smallest increase in protein dynamics.
- Zwitterionic compounds (MIL, HPS) exhibited minimal effects on albumin stiffness and mobility in blood plasma.
Conclusions:
- MIL's interaction with erythrocyte membranes is comparable to zwitterionic surfactants.
- Zwitterionic compounds, including MIL, appear to have lower hemolytic potential than some ionic surfactants.
- Understanding these interactions is crucial for assessing the safety and efficacy of leishmanicides.
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