Lipid molecular manipulation

Molecular Manipulation on the Self-Spreading Lipid Bilayer... 

The most intriguing aspect of the self-spreading lipid bilayer is that any molecule in the bilayer can be transported without any external bias. The unique characteristic of the spreading layer offers the chance to manipulate molecules without applying any external biases. This concept leads to a completely non-biased molecular manipulation system in a microfluidic device. For this purpose, the use of nano-space, which occasionally offers the possibility of controlling molecular diffusion dynamics, would be a promising approach. 

The adamantane moiety is of medicinal chemical interest because of its inertness, compactness relative to lipid solubilizing character, and symmetry. Considerable interest, therefore, was engendered by the finding that amantadine (78) was active for the chemoprophylaxis of influenza A in man. There are not many useful chemotherapeutic agents available for the treatment of communicable viral infections, so this finding led to considerable molecular manipulation. The recent abrupt end of the National Influenza Immunization program of 1976 prompted a new look at the nonvaccine means for prophylaxis or treatment of respiratory tract infections due to influenza A, especially in that the well-known antigenic shift or drift of the virus obviates usefulness of the vaccine but not amantadine. 

Molecular manipulation resulting in a lipid/water-solubility suitable for penetration of both lipid membranes and the water compartments such as the interstitial fluids will enhance absorption and facilitate distribution over the various... 

For an artificial lipid bilayer of any size scale, it is a general feature that the bilayer acts as a two-dimensional fluid due to the presence of the water cushionlayer between the bilayer and the substrate. Due to this fluidic nature, molecules incorporated in the lipid bilayer show two-dimensional free diffusion. By applying any bias for controlling the diffusion dynamics, we can manipulate only the desired molecule within the artificial lipid bilayer, which leads to the development of a molecular separation system. 

Recently, a quantitative electrospray ionization/mass spectrometry method (ESI/MS) has been developed to analyze the molecular profile, or hpidome of different lipid classes in very small samples. In this method, total lipid extracts from tissues or cultured cells can be directly analyzed. By manipulating the ionization method, the mass spectrographs of polar or even non-polar lipids can be obtained [8]. This method and the use of lipid arrays allow precise and quantitative identification of the lipid profile of a given tissue, and map functional changes that occur. 

Atmospheric Pressure Chemical Ionization (APCI)/MS APCI/MS is used to analyze compounds of intermediate molecular weight (100-1,500 da) and intermediate polarity and is particularly useful for the analysis of biochemicals such as triacylglycerides, carotenoids, and lipids (Byrdwell, 2001). For volatile, nonpolar compounds of low molecular weight, GC/MS is preferred to APCl/MS whereas APl-electrospray/ MS provides better results for larger, more polar materials. The selection of APCl/MS over GC/MS or APl-electrospray/MS depends on the compounds to be analyzed. Many LC/MS instruments can be easily switched between APCl/MS and APl-electrospray/MS so that it can be rapidly determined which ionization process is more suitable to a given chemical. Additional manipulations such as pre and postcolumn derivatization reactions (Nagy et al., 2004 Peters et al., 2004) or coulometric oxidation (Diehl et al., 2001) can make the chemicals of interest more amenable to detection by APCI. 

The prescient remarks of Fredrickson in 1961 that investigations into Tangier disease will shed light on poorly understood lipid and fat metabolic pathways have now been borne out. An unanticipated bonus has been the identification of a molecular target for pharmacological manipulation might help lower the risk of CAD in the normal population. 

Self-assembled monolayers have recently attracted much attention as a new methodology for molecular assembly [249, 342]. They enable highly organized chemical binding of molecules of interest to the surfaces of, e.g., metals, semiconductors, and insulators. The well-ordered structure of self-assembled monolayers is in sharp contrast with conventional Langmuir-Blodgett films and lipid bilayer membranes in terms of stability, uniformity, and manipulation. Functional molecules can be arranged unidirectionally at the molecular level on substrates when substituents which will self-assemble on the substrates are attached to a terminal of the molecules. The wide variety of examples reported to date include porphyrins and metalloporphyrins in self-assembled monolayers [299-339]. 

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