Chlorpromazine interaction with glycerophospholipid liposomes studied by magic angle spinning solid state (13)C-NMR and differential scanning calorimetry
Autor: | Stig Are Gundersen, Holm Holmsen, Willy Nerdal, Harald Høiland, Vidar A.T. Thorsen |
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Rok vydání: | 2000 |
Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Chlorpromazine Biophysics Analytical chemistry Phospholipid Glycerophospholipids Biochemistry chemistry.chemical_compound Differential scanning calorimetry Magic angle spinning Lipid bilayer Chlorpromazine-HCl interaction Liposome Carbon Isotopes Calorimetry Differential Scanning Bilayer technology industry and agriculture Temperature Cell Biology Nuclear magnetic resonance spectroscopy DPPC/DMPC liposome Crystallography Psychotropic drug chemistry Dipalmitoylphosphatidylcholine Cross polarization solid state magic angle spinning 13C-nuclear magnetic resonance spectroscopy DPPC/PS liposome Liposomes lipids (amino acids peptides and proteins) |
Zdroj: | Biochimica et biophysica acta. 1464(1) |
ISSN: | 0006-3002 |
Popis: | Phosphatidylserine (PS) extracted from pig brain and synthetic dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) were used to make DPPC/DMPC and DPPC/PS large unilamellar liposomes with a diameter of approximately 1 microm. Chlorpromazine-HCl (CPZ), an amphipathic cationic psychotropic drug of the phenothiazine group, is known to partition into lipid bilayer membranes of liposomes with partition coefficients depending on the acyl chain length and to alter the bilayer structure in a manner depending on the phospholipid headgroups. The effects of adding CPZ to these membranes were studied by differential scanning calorimetry and proton cross polarization solid state magic angle spinning (13)C-nuclear magnetic resonance spectroscopy (CP-MAS-(13)C-NMR). CP-MAS-(13)C-NMR spectra of the DPPC (60%)/DMPC (40%) and the DPPC (54%)/DMPC (36%)/CPZ (10%) liposomes, show that CPZ has low or no interaction with the phospholipids of this neutral and densely packed bilayer. Conversely, the DPPC (54%)/PS (36%)/CPZ (10%) bilayer at 25 degrees C demonstrates interaction of CPZ with the phospholipid headgroups (PS). This CPZ interaction causes about 30% of the acyl chains to enter the gauche conformation with low or no CPZ interdigitation among the acyl chains at this temperature (25 degrees C). The DPPC (54%)/PS (36%)/CPZ (10%) bilayer at a sample temperature of 37 degrees C (T(C)=31.2 degrees C), shows CPZ interdigitation among the phospholipids as deduced from the finding that approximately 30% of the phospholipid acyl chains carbon resonances shift low-field by 5-15 ppm. |
Databáze: | OpenAIRE |
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