Cell membrane penetration

The second property of importance for bioavailability is the polar surface area (PSA) that is associated with intestinal absorption and cell membrane penetration by passive transport. Compounds with a high polar surface are less likely to penetrate the lipophilic environment of the cell membranes by passive transport. Like the logP, PSA can be computed by summing up fragment contributions (8) with H-bonding fragments as the main contributor. 

Vimses are made up of a protein capsule, some with a lipoprotein envelope around it, containing genetic material (either DNA or RNA), with maybe a few enzymes but very little else and hence they are not considered to be cells, but, rather, infectious particles. Viruses are able to bind to cell membranes, penetrate and infect cells of other organisms. Viruses are intracellular parasites they cannot replicate themselves without using the contents of the host cell to synthesize the cellular components necessary for their reproduction. This makes the development of effective antiviral drugs that do not damage healthy host cells very difficult. 

Mechanisms Amantadine and rimantadine inhibit the first steps in replication of the influenza A and rubella viruses (Figure 49-1). These steps involve viral adsorption to the host cell membrane, penetration into the cell via endocytosis. and viral particle uncapping. The inhibitory action of these drugs may be due to their alkaline reaction, which raises the endo-somal pH. At low concentrations, amantadine also binds to a specific protein in the surface coat of the influenza virus to prevent fusion. Drug-resistant influenza A virus mutants can emerge and infect contacts of patients in treatment. 

One of the most attractive properties of stapled peptides is their improvement in cell membrane penetration, which is a well-known disadvantage of peptides and their rnimics in the application of these drugs to intracellular targets. In order to track and quantify the stapled peptide penetrating the membrane, a fluorescent tag (such as FITC) is conjugated to the N-terminus of the stapled peptide. As a control, the unstapled peptide is also labeled. Then the cellular update of FITC-labeled peptides can be examined using confocal microscopy and quantified by flow cytometry these stapled peptides are reported to be localized to the cytoplasm with minimum distribution to the nucleus when the confocal experiment is coupled with nuclear staining. 

Review articles have appeared which discuss the effects of PG s on blood pressure, " platelet formation, cell-membrane penetration by calciiun... 

The kinetic data were used to develop a mechanism where the rate was primarily influenced by a combination of the following factors adsorption of substrate to the surface of the cell membrane, penetration of the lipid layer of the membrane, and diffusion through hydrophilic pores in the membrane (Banerjee et al. 1984). It was postulated that the rates of degradation of the phenols in TABLE 1 owed their dependence on Kq to rate limiting movement through the lipid layer. 

Trewyn, B.G., Nieweg, ).A., Zhao, Y. and lin, V.S.Y. (2008) Biocompatible mesoporous silica nanoparticles with different morphologies for animal cell membrane, penetration. Chemical Engineering Journal, 137(1), 23-9. 

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