Drug-Membrane Interactions

Автор(ы):Seydel K. Joachim
06.10.2007
Год изд.:2002
Описание: What is the relevance of artificial membranes, of phospholipid bilay-ers? Do such systems disclose enough or the right biophysical properties of real membranes that would enable us to design compounds interacting with such sophisticated targets like membranes? Those are the questions that the volume on Drug-Membrane Interactions by Joachim Karl Seydel and Michael Wiese is tracing. After a short introduction into membrane architecture and properties, biophysical analytics is the main topic of chapters 2 and 3. The authors go deep into the discussion of octanol/water modelling of partitioning of compounds into membranes. The fourth chapter is devoted to transport whereas target interaction and hence the pharmacodynamics is reflected in chapter 5. An outlook is given in chapter 6, where virtual membranes play the main role. Michael Wiese gives us the state of the art of modelling membranes and their interactions with ligands.
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Drug-Membrane Interactions — обложка книги.
1 Function, Composition, and Organization of Membranes [2]
  1.1 The Physiology of Cells and the Importance of Membranes for their Function [2]
  1.2 Composition and Organization of Membranes [3]
    1.2.1 Mammalian Membranes [3]
    1.2.2 Bacterial Membranes [14]
    1.2.3 Fungal Membranes [17]
    1.2.4 Artificial Membranes, Liposome Preparation, and Properties [18]
  1.3 Dynamic Molecular Organization of Membranes [21]
    1.3.1 Thermotropic and Lysotropic Mesomorphism of Phospholipids [21]
    1.3.2 Phase Separation and Domain Formation [24]
  1.4 Possible Effects of Drugs on Membranes and Effects of Membranes on Drag Molecules [27]
        References [30]
2 Octanol-Water Partitioning versus Partitioning into Membranes [35]
        References [49]
3 Analytical Tools for the Analysis and Quantification of Drug-Membrane Interactions [51]
  3.1 High-performance Liquid Chromatography (HPLC) [52]
    3.1.1 Determination of the Retention Time on "Artificial Membrane" Columns [52]
  3.2 Displacement of 45Ca2+ from Phospholipid Head Groups [54]
    3.2.1 Studies of Drug-Membrane Interactions using Phospholipid Monolayers [54]
  3.3 Differential Scanning Calorimetry (DSC) [58]
    3.3.1 Phase Transition and Domain Formation [58]
  3.4 Fluorescence Techniques [75]
  3.5 Fourier Transform Infrared Spectroscopy (FT-IR) [77]
  3.6 Electron Spin Resonance (ESR) [79]
  3.7 Small-angle Neutron and X-ray Diffraction [83]
  3.8 Nuclear Magnetic Resonance (NMR) [87]
    3.8.1 Study of Membrane Polymorphism by 31P-NMR [88]
    3.8.2 Effect of Cholesterol and Diacylglycerols [89]
    3.8.3 Effect of Drags [92]
    3.8.3.1 31P-NMR forthe Study of Changes in Orientation of Phospholipid Head Group [92]
    3.8.4 Determination of Drag Transmembrane Transport [96]
    3.8.5 JH-NMR in Combination with Pr3+ for the Study of Drag Location [100]
    3.8.6 The Use of 2H-NMR and 13C-NMR to Determine the Degree of Order and the Molecular Dynamics of Membranes [103]
    3.8.7 Change in relaxation rate, 1/T2: a Method of Quantifying Drug-Membrane Interaction [105]
    3.8.8 NOE-NMR in the Study of Membrane-induced Changes in Drag Conformation [112]
  3.9 Circular Dichroism (CD) [116]
  3.10 UV Spectroscopy [117]
  3.11 Combined Techniques for Studying Drug-Membrane Interaction [120]
    3.11.1 Combination of DSC and NMR [120]
    3.11.2 Combination of DSC and X-ray Diffraction [122]
    3.11.3 Combination of DSC and ESR [124]
    3.11.4 Combination of DSC and Fluorescence [126]
    3.11.5 Combination of FT-IR and NMR [129]
    3.11.6 Combination of UV and 2H-NMR [129]
    3.11.7 Combination of DSC, FT-IR, and NMR [130]
  3.12 Summary [132]
        References [135]
4 Drug-Membrane Interaction and Pharmacokinetics of Drugs [141]
  4.1 Drag Transport [141]
    4.1.1 Absorption Models [148]
      4.1.1.1 Caco-2 Cells as an Absorption Model [148]
      4.1.1.2 Parallel Artificial Membrane Permeation Assay (PAMPA) [155]
      4.1.1.3 Surface Plasmon Resonance Biosensor Technique [155]
      4.1.1.4 The Use of IAM Columns [157]
      4.1.1.5 Partitioning into Immobilized Liposomes [159]
    4.1.2 Computational Methods, QSAR [161]
  4.2 Drag Distribution [168]
    4.2.1 Distribution into the Brain Compartment [168]
    4.2.2 Distribution, Localization, and Orientation of Drugs in Various Tissues and Membranes [173]
    4.2.3 Distribution in vivo [180]
  4.3 Uptake into and Distribution within Bacterial Cells [187]
    4.3.1 Diffusion Through the Outer Asymmetric Core of E. coli [189]
    4.3.2 Self-promoted Uptake of Antibacterial Peptides [196]
  4.4 Drug Accumulation, Toxicity, and Selectivity [199]
    4.4.1 Selectivity [211]
        References [212]
5 Drug-Membrane Interactions and Pharmacodynamics [217]
  5.1 Drag Efficacy [217]
    5.1.1 Effect on Membrane-integrated Enzymes [218]
      5.1.1.1 Activation and Inhibition of Protein Kinase С (РКС) [218]
      5.1.1.2 Inhibition of Phospholipase A2 (PLA2) [219]
      5.1.1.3 Drag-Membrane Interactions and Inhibition of Na+,K+-ATPase [220]
    5.1.2 Release of Pharmacological Response [223]
      5.1.2.1 Effect of Anesthetics [223]
      5.1.2.2 Negative Chronotropic (Cardiodepressant) Effect [228]
    5.1.2.3 Anti-inflammatory Effect [229]
      5.1.2.4 Effect of Antiarrhythmics [231]
      5.1.2.5 Calcium-Channel Blocking Activity [232]
      5.1.2.6 a-Adrenoceptor Agonist Activity [233]
      5.1.2.7 Anticonvulsive Effect [234]
      5.1.2.8 Antioxidant Effect [236]
      5.1.2.9 Antineoplastic Activity of Ether Phospholipids [236]
      5.1.2.10 Antimalarial Activity of Chloroquine [237]
      5.1.2.11 Conformation of Acetogenin Derivatives in Membranes and the Relation to Cytotoxicity [238]
      5.1.2.12 A Membrane-forming and Inflammation-inducing Bacterial Macromolecule [238]
      5.1.2.13 Drug-Membrane Interactions involved in Alzheimer's Disease [239]
  5.2 Drag Resistance [241]
    5.2.1 Bacterial Cells [241]
    5.2.2 Reversal of Multidrug Resistance in Tumor Cells [245]
    5.2.3 Proposed Mechanisms of Action [247]
    5.2.4 Change in Composition of Membranes and Influence on P-gp, Cytotoxic Agents, and MDR-reversing Drugs [250]
      5.2.4.1 Comparison of Lipid Composition of Sensitive and Resistant Cells [250]
      5.2.4.2 Membrane Composition and Functioning of Membrane-embedded Proteins [254]
    5.2.5 Membrane Composition, Drug Binding, and Transport Kinetics [259]
    5.2.6 SARs and QSARs for Cytotoxic Agents and MDR Modifiers [276]
        References [285]
6 Computer Simulation of Phospholipids and Drug-Phospholipid Interactions [291]
  6.1 Modeling Strategies for Studying Phospholipids and Drug-Phospholipid Interactions [291]
    6.1.1 Types of Representation of the Simulated System [292]
      6.1.1.1 Mean Field Simulations [292]
      6.1.1.2 All-atom Simulations [293]
    6.1.2 Monte Carlo Simulations [295]
    6.1.3 Molecular Dynamics Simulations [296]
      6.1.3.1 Starting Structure, and Equilibrium Time [298]
      6.1.3.2 Boundary Conditions [300]
      6.1.3.3 Long-range Electrostatics and Non-bonded Cut-off [300]
      6.1.3.4 Kind of Simulation System [302]
  6.2 Computer Simulations with Phospholipids [305]
    6.2.1 Distribution of Solutes [305]
    6.2.2 Mechanism of Diffusion through Phospholipid Membranes [309]
    6.2.3 Small Molecules and their Interaction with Phospholipids [314]
      6.2.3.1 Anesthetics [314]
      6.2.3.2 Dihydropyridines [315]
    6.2.4 Effect of Cholesterol on Membrane Structure [316]
    6.2.5 Interactions of peptides with phospholipids [322]
      6.2.5.1 Mean Field Simulations [322]
      6.2.5.2 All-atom Simulations [325]
    6.2.6 Simulations of Pore-forming Peptides and of the Diffusion of Ions through Ion Channels [327]
    6.2.7 Non-equilibrium Molecular Dynamics Simulations [331]
  6.3 Concluding Remarks [332]
        References [334]
Index [337]
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