Mixed phospholipids

Imavist/Imagent/mixed phospholipid QFi4 New Drug Application [40]... 

Lonchin, S., Luisi, P. L., Walde, P, and Robinson, B. H. (1999). A matrix effect in mixed phospholipid/fatty acid vesicle formation. J. Phys. Chem. B, 103, 10910-16. 

A2 in mixed phospholipid systems and the kinetics and migration of the acyl and phosphorus group of the lyso-phospholipid products. 

Levy M. Y., Benita, S., and Baszkin, A. (1991), Interactions of a non-ionic surfactant with mixed phospholipid-oleic acid monolayers. Studies under dynamic conditions, Coll. Surf., 59, 225-241. 

In hPL Winkler et al. (1990) originally suggested that the amides of Leu-154 (structurally equivalent to 145 in RmL) and Phe-78 may make up the oxyanion hole, van Tilbeurgh et al. (1993) succeeded in the structural characterization of a complex of hPL with bovine procolipase (see Section III,C for the description of this cofactor and its function) crystallized in the presence of mixed phospholipid/bile salt micelles. In this complex hPL assumes the active conformation, and it is clear that after the accompanying conformational change the amides of Leu-154 and Phe-78 can indeed serve as electrophiles for the oxyanion. 

The monoacylglycerol 3 is insoluble in water and has to be presented in micelles or lipid complexes (e.g. droplets) to be acceptable as lipase substrate. To generate the substrate, 3 was incorporated into mixed phospholipid micelles. To prepare these micelles, a solution of 3 in Cl I Cl, was added to a solution of phospholipids (phosphocholine, phosphoinositol) in a buffer system. The organic solvent was purged with nitrogen and the organic mixture was sonicated. To our surprise, the development of mixed micelles was accompanied by a color shift from yellow to red (Fig. 7.2, see p. 123). 

It was found that the presence of cholesterol markedly influences the hydrogenation of mixed phospholipid dispersions [12] because it restricts partition of the catalyst into the lipid bilayer structure. It was also found that no dihydrocholesterol forms during hydrogenation of the phospholipid, showing that cholesterol is not a substrate for reaction under the conditions employed. 

Liposomes were discovered by Dr. Alec Bangham in 1961. During his studies on phospholipids and blood clotting, he found that if he mixed phospholipids and water, tiny phospholipid bilayer sacs, called liposomes, would form spontaneously. Since that first observation, liposomes have been developed as efficient delivery systems for everything from antitumor and antiviral drugs, to the hair-loss therapy minoxidil ... 

Lipid Vesicles. Lipid vesicles are composed of lipid bilayers that separate the bulk aqueous medium from an entrapped aqueous compartment. They are easily prepared by mixing phospholipid with the appropriate aqueous buffer. The vigor of the mixing operation determines the number and size distribution of bilayers that comprise each vesicle. For example, extensive sonication of egg phosphatidylcholine produces an optically clear suspension... 

The preparation methods of these vesicles are various. In some cases, the liposomal suspension is firstly prepared and then amphiphilic CyDs are inserted inside the phospholipid-bilayer, for example by sonication [93]. Another method mixes phospholipid (+/— cholesterol) and amphiphilic CyD solutions, to form hposomes by conventional methods [92, 94]. Lastly, vesicles consisting of bilayers of purely amphiphilic CyDs as raw material can be prepared applying a technique used to prepare hposomes, i.e. hydration of lipidic film followed by sonication [99-101]. 

It has been mentioned previously that sterols were readily incorporated into lecithin or mixed phospholipid monolayers [194—196]. The area of sterol-containing films was smaller than that calculated for the separate components, indicating some kind of interaction between the two molecules [221,222]. Sterols have also been shown to reduce the phase transitions of pure lecithin dispersions [214]. It has been suggested that cholesterol modifies the fluidity of the hydrocarbon chains of the phospholipid molecules by disrupting the crystalline chain lattice of the gel phase and by inhibiting the flexing of the chains in the dispersed liquid-crystalline phase [221—226]. 

The interaction of cholesterol with membrane phospholipids is further complicated by findings that cholesterol is not necessarily uniformly dispersed in mixed phospholipid bilayers. In DSC studies on bilayers composed of two lipids of the same class, but with melting points sufficiently different to give two peaks in the calorimeter, cholesterol associates with the lower melting point lipid. That is, it appears to be frozen out of solid crystalline regions of the bilayer. In addition, however, cholesterol has a preference for specific lipid classes that overides its preference for lower melting point lipids... 

Mix phospholipids with the fluorescent probe at a mole ratio of 50-100 1 (lipidstprobe) in a vessel resistant to chloroform and suitable for somcation To make 1 mL of a vesicle suspension, use 5-15 pmol of lipids. 

Lonchin et al. (27) have also studied the matrix effect of phospholipid vesicles. These authors investigated the formation of mixed phospholipid/fatty acid vesicles by using a combination of kinetic and structural methods to study the process of spontaneous formation of vesicles on addition of oleate micelles to preexisting vesicles of l-palmitoyl-2-oleoyl-.yyn-glycero-3-phosphocholine (POPC). 

Wiener, J. R., Pal, R., Barenholz, Y., and Wagner, R. R., 1983, Influence of the peripheral matrix protein of vesicular stomatitis virus on the membrane dynamics of mixed phospholipid vesicles Fluorescence studies. Biochemistry 22 2162. 

TV. Fatty-Acid and Mixed Phospholipid/Fatty Acid... 

Izvekov, S., 8c Voth, G. A. (2006). Multiscale coarse-graining of mixed phospholipid/cholesterol bilayers. Journal of Chemical Theory and Computation, 2, 637. 

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