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Lipids membrane crossing

Due to the predominantly hydrophilic nature of PNAs they do not readily cross lipid membranes [93] and enter living cells [94]. Therefore in order to explore the ex vivo and in vivo potential of PNA as an antisense and/or antigene reagent, a number of different transfection protocols have been devised over recent years. [Pg.166]

Figure 3.3 Molecular structure of G-protein-coupled receptors. In (a) the electron density map of bovine rhodopsin is shown as obtained by cryoelectron microscopy of two-dimensional arrays of receptors embedded in lipid membrane. The electron densities show seven peaks reflecting the seven a-helices which are predicted to cross the cell membrane. In (b) is shown a helical-wheel diagram of the receptor orientated according to the electron density map shown in (a). The diagram is seen as the receptor would be viewed from outside the cell membrane. The agonist binding pocket is illustrated by the hatched region between TM3, TM5 and TM6. (From Schertler et al. 1993 and Baldwin 1993, reproduced from Schwartz 1996). Reprinted with permission from Textbook of Receptor Pharmacology. Eds Foreman, JC and Johansen, T. Copyright CRC Press, Boca Raton, Florida... Figure 3.3 Molecular structure of G-protein-coupled receptors. In (a) the electron density map of bovine rhodopsin is shown as obtained by cryoelectron microscopy of two-dimensional arrays of receptors embedded in lipid membrane. The electron densities show seven peaks reflecting the seven a-helices which are predicted to cross the cell membrane. In (b) is shown a helical-wheel diagram of the receptor orientated according to the electron density map shown in (a). The diagram is seen as the receptor would be viewed from outside the cell membrane. The agonist binding pocket is illustrated by the hatched region between TM3, TM5 and TM6. (From Schertler et al. 1993 and Baldwin 1993, reproduced from Schwartz 1996). Reprinted with permission from Textbook of Receptor Pharmacology. Eds Foreman, JC and Johansen, T. Copyright CRC Press, Boca Raton, Florida...
P-gp substrates are in general either neutral or cationic at physiological pH (weak bases). Weak bases can cross the lipid membrane in the uncharged form and reprotonate in the negatively charged cytosolic leaflet of the membrane. With a few exceptions (e.g., the tetraphenyl phosphonium ion, which can reach the cytosolic membrane leaflet due to charge delocalization [70]), permanently charged cations do not cross the cell membrane and therefore cannot interact with P-gp in intact cells. They can, however, insert into the cytosolic leaflet in inside-out cellular vesicles and are then transported by P-gp [42, 71]. [Pg.475]

Use of a hydrocarbon solvent such as cyclohexane can discriminate these compounds either as the only measured value or as a value to be subtracted from the octanol value (Alog P) [19-21]. Unfortunately, cyclohexane is a poor solvent for many compounds and does not have the utility of octanol. Groups which hydrogen bond and attenuate actual membrane crossing compared to their predicted ability based on octanol are listed in Figure 1.4. The presence of two or more amide, carboxyl functions in a molecule will significantly impact on membrane crossing ability and will need substantial intrinsic lipophilicity in other functions to provide sufficient hydrophobicity to penetrate the lipid core of the membrane. [Pg.7]

Although artificial lipid membranes are almost impermeable to ions, biological membranes contain ion channels that selectively allow individual ion types to pass through (see p. 222). Whether an ion can cross this type of membrane, and if so in which direction, depends on the electrochemical gradient—i.e., on the concentrations of the ion on each side of the membrane (the concentration gradient) and on the difference in the electrical potential between the interior and exterior, the membrane potential. [Pg.126]

Figure 5.25 — Flow-through ion-selective optrode based on a multilayer lipidic membrane prepared by the Langmuir-Blodgett method. (A) Cross-sectional view of the composite six-layer membrane (four layers of arachidic acid/ valinomycin covered by an arachidic acid and rhodamine dye bilayer). (B) Optical arrangement integrated with the sensor, which is connected to a flow system. LS light source Ml and M2 excitation and emission monochromator, respectively FI and F2 primary filters M mirror LB lipid-sensitive membrane in a glass platelet FC flow-cell A amplifier D display P peristaltic pump. (Reproduced from [107] with permission of the Royal Society of Chemistry). Figure 5.25 — Flow-through ion-selective optrode based on a multilayer lipidic membrane prepared by the Langmuir-Blodgett method. (A) Cross-sectional view of the composite six-layer membrane (four layers of arachidic acid/ valinomycin covered by an arachidic acid and rhodamine dye bilayer). (B) Optical arrangement integrated with the sensor, which is connected to a flow system. LS light source Ml and M2 excitation and emission monochromator, respectively FI and F2 primary filters M mirror LB lipid-sensitive membrane in a glass platelet FC flow-cell A amplifier D display P peristaltic pump. (Reproduced from [107] with permission of the Royal Society of Chemistry).
Fig. 5a—c. Orientation of amphiphilic compounds in model membranes33 a) monolayer at the gas/water interface b) bimolecular lipid membrane (BLM) c) liposomes. Between b and c a cross section through the bilayer of BLM or liposomes is shown... [Pg.11]

Lipid membranes were fitted on a multichannel electrode. Figure 5 shows a front view and a cross section of the electrode. The electrode was made from Ag wires, which were 1.5 mm in diameter, embedded in a basal acrylic board. The lipid membranes cut into rectangle pieces were put on the Ag wires, and then the electrode was dried in air for 1 hour and dipped in 1 mM KC1 solution. [Pg.382]

In general, there are four main ways by which small molecules cross biological lipid membranes ... [Pg.80]

Only relatively small uncharged or hydrophobic molecules (H20, 02, C02, other gases, urea and ethanol) cross the lipid bilayer by simple diffusion. No membrane proteins are involved, so there is no specificity. The molecule in aqueous solution on one side of the membrane dissolves into the lipid bilayer, crosses it, and then dissolves into the aqueous solution on the opposite side. The rate of diffusion is directly proportional to the concentration gradient of the molecule across the membrane and the process is not saturable (Fig. la). [Pg.132]

Despite the presence of a large concentration of carbon dioxide in the blood (ca. 1 him), it has been reported that peroxynitrite can diffuse across the red-blood-cell membrane and react with oxyHb [24]. The anionic form (ONOO-) crosses the erythrocyte membrane by using the anion channel band 3 whereas peroxynitrous acid crosses the lipid membranes by rapid passive diffusion [24]. [Pg.195]

Those that are less lipophilic and possess smaller cross-sectional areas at the air-water interface. These drugs interact readily with lipid membranes and their high pit, values allow a reprotonation at the CNS side of the membrane,... [Pg.171]

The transport of molecules across biological cell membranes and biomimetic membranes, including planar bilayer lipid membranes (BLMs) and giant liposomes, has been studied by SECM. The approaches used in those studies are conceptually similar to generation-collection and feedback SECM experiments. In the former mode, an amperometric tip is used to measure concentration profiles and monitor fluxes of molecules crossing the membrane. In a feedback-type experiment, the tip process depletes the concentration of the transferred species on one side of the membrane and in this way induces its transfer across the membrane. [Pg.232]

Figure 33 Representative 2D H-31 correlation spectra of hydrated lipid membranes with a mixing time of 64 ms. (A) POPC and (B) POPE/POPG (3 2) membrane. H peak assignment is indicated. POPC lacks a water-31P cross peak. Extending the mixing time to 225 ms still yields no water cross peak. Spectra were measured under 4.0 kHz MAS. Taken from Ref. [119]. Figure 33 Representative 2D H-31 correlation spectra of hydrated lipid membranes with a mixing time of 64 ms. (A) POPC and (B) POPE/POPG (3 2) membrane. H peak assignment is indicated. POPC lacks a water-31P cross peak. Extending the mixing time to 225 ms still yields no water cross peak. Spectra were measured under 4.0 kHz MAS. Taken from Ref. [119].
Q12 Oestrogens are involved in regulation of menstrual cycle, development of secondary sex characteristics in females and changes in the uterine lining. It affects the metabolism of minerals, carbohydrate, protein and lipid. Oestrogen crosses the cellular membrane and binds to receptors in the nucleus these receptors are present in both males and females. In females they are located... [Pg.307]

Figure 2.6. The role of lipid membranes in drag distribution, a Structure of phosphatidylcholine (left), and schematic of a lipid bilayer (right). The hydrophobic interior phase represents the kinetic barrier to drag absorption and distribution. b Drag diffusion across lipid bilayers. Partition into the bilayer is the rate-limiting step. Hydrophilic drag molecules (left) will not efficiently partition into the hydrophobic phase and therefore can t get across the membrane easily. In contrast, hydrophobic molecules (right) will enter the membrane readily and therefore will cross the membrane more efficiently. Figure 2.6. The role of lipid membranes in drag distribution, a Structure of phosphatidylcholine (left), and schematic of a lipid bilayer (right). The hydrophobic interior phase represents the kinetic barrier to drag absorption and distribution. b Drag diffusion across lipid bilayers. Partition into the bilayer is the rate-limiting step. Hydrophilic drag molecules (left) will not efficiently partition into the hydrophobic phase and therefore can t get across the membrane easily. In contrast, hydrophobic molecules (right) will enter the membrane readily and therefore will cross the membrane more efficiently.
The particular way in which the walls of the blood vessels in the central nervous system are constructed results in their being impermeable to many substances, thereby limiting the ability of molecules to pass from the blood into the brain. This phenomenon is called the blood-brain barrier. Molecules may cross the blood-brain barrier by mechanisms of active transport, or by being sufficiently lipid soluble that they can diffuse through the hydrophobic core of the lipid membranes that form the boundaries of the cells composing the blood-brain barrier. Most psychoactive drugs are sufficiently lipid soluble that they can pass from the blood into the brain by passive diffusion. [Pg.104]


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See also in sourсe #XX -- [ Pg.312 ]




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Crossing membranes

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