Lipids synthetic phospholipids

The system reported by Avdeef and co-workers [25-28,556-560] is an extension of the Roche approach, with several novel features described, including a way to assess membrane retention [25-28,556,557] and a way to quantify the effects of iso-pH [558] and gradient pH [559] conditions applied to ionizable molecules. A highly pure synthetic phospholipid, dioleoylphosphatidylcholine (DOPC), was initially used to coat the filters (2% wt/vol DOPC in dodecane). Other lipid mixtures were subsequently developed, and are described in detail in this chapter. 

Abstract To understand how membrane-active peptides (MAPs) function in vivo, it is essential to obtain structural information about them in their membrane-bound state. Most biophysical approaches rely on the use of bilayers prepared from synthetic phospholipids, i.e. artificial model membranes. A particularly successful structural method is solid-state NMR, which makes use of macroscopically oriented lipid bilayers to study selectively isotope-labelled peptides. Native biomembranes, however, have a far more complex lipid composition and a significant non-lipidic content (protein and carbohydrate). Model membranes, therefore, are not really adequate to address questions concerning for example the selectivity of these membranolytic peptides against prokaryotic vs eukaryotic cells, their varying activities against different bacterial strains, or other related biological issues. 

Finally, besides conventional liposomes that are made from natural (e.g., egg yolk and soybean) or synthetic phospholipids, novel liposomes called archaeosomes that are prepared from the polar ether lipids extracted from various archaeobacteria proved also interesting for the design of vaccines as peptide antigen carriers (71) and as powerful self-adjuvanting vaccine delivery vesicles that promote both humoral and cell-mediated immunity (72). Related to this, one can mention that pseudopeptides, which are less prone to proteolysis when conjugated to liposomes, were also competent in triggering a humoral immune response (73). 

Roseman, A., Lentz, B. R., Sears, B., Gibbes, D., and Thompson, T. E. (1978). Properties of sonicated vesicles of three synthetic phospholipids. Chem. Phys. Lipids, 21, 205-22. 

Figure 9. Scans of synthetic phospholipids in water taken with a Perkin-Elmer DSC IB differential scanning calorimeter. Lipid concentrations were 10-15% by weight...

Since the synthesis of glycolipids involves the synthesis of both the lipid and the oligosaccharide portions, we shall also discuss that part of the recorded lipid synthetic work which has involved the use of carbohydrates. In fact, some of the first-recorded applications of carbohydrate molecules as chiral templates are to be found in the lipid field particularly with the use of 1,2 5,6-di-O-isopropylidene-D-mannitol [33] as a precursor of chiral glycerol derivatives for the synthesis of phospholipids and glycolipids based on glycerol and with the use of glucosamine derivatives for the synthesis of phytosphingosines [34] and since this area has not previously been reviewed, it will be treated with a more historical perspective. 

Menger had previously shown that the ion flux across synthetic phospholipids could be promoted by attaching alkyl groups of various sizes to the hydrophobic portion of the lipid, presumably by creating reversible defects in the bilayer.34... 

Synthetic phospholipids are commercially available and they contain polar heads occurring in nature and and the same type of fatty acid in both, 9 -l and sn-2 sites. The acyl chains may be mainly myristoyl (C14 0), palmitoyl (C16 0), olcoyl (C16 l) or stearoyl (C18 0) residues. The physicochemical characteristics of the lipidic bilayers that are prepared from synthetic phospholipids are well defined. The lipid composition influences many physical properties of model membranes and it has been shown that single synthetic lipids or mixtures of short and long fatty acid chains can produce stable lipidic bilayers and liposomes. 

Membranes naturally tend to form closed structures, to avoid exposing the hydrophobic ends of lipid bilayers to the solvent. Synthetic closed structures, called liposomes, can be made with membrane fragments or synthetic phospholipids. Liposomes can be made to contain compounds buried in the membrane or totally enclosed and are a... 

Synthetic phospholipids mixtures were also shown to form lyotropic liquid crystals with interesting properties. For example ternary lipid mixtures comprising of two lipids, dioleoylphosphatidylcholine (DOPC), dioleoylglycerol (DOG), and cholesterol, of molar ratios 1 2 1 and 1 2 2, in excess water induced formation of three dimensional (3D) hexagonal mesophases [12], Other synthetic such as polyoxyethylene-10-oleyl ether [13] also can form LLC but since these structures were less studied and have less potential to serve as delivery vehicles they will not be discussed in this chapter. 

LB films of artificial lipids transferred onto electrode substrates could be used as glucose [14] and calcium ion [15] sensors and for hydrogen evoluhon [16]. Okahata etal. coated a Sn02 electrode with LB films of synthetic phospholipids [15]. Oxidation peak currents of a maker ion ([Fe(CN)6] / - ) in the aqueous phase through the hpid films increased with the addition of Ca " " ions only when the LB films were in the fluid hquid crystalline phase above the phase transition... 

The model lipoproteins are recombinants of apoA-II and the synthetic phospholipids, DMPC or l-palmitoyl-2-palmitoleoylphosphatidylcho-line, PPOPC. The rates of transfer (see Table 9) are influenced by the properties of the lipid-protein surface of the recombinant donor. Thus, the addition of two methylene units to the acyl chains decreases the rate of desorption from DMPC by a factor of 8-10, whereas, the addition of a double bond increases the rate by a factor of 10. When a PPOPC matrix is used, the change is about a... 

In the case of HDL, there are subtle changes of structure associated with changing lipid patterns as the particles evolve. Soluble HDL apolipo-proteins interact with well-defined synthetic phospholipids to form a disclike structure similar to that observed in vivo (section 5.3.5). In the absence of neutral lipids, the structural organization is dominated by the bilayer formation of the phospholipids. As neutral lipids (cholesterol esters and triacylglycerols) are incorporated into the core, the particles assume a spherical morphology that is governed by the hydrophobic interactions of the core lipids. 

Artificial membrane systems can be prepared by appropriate techniques. These systems generally consist of mixtures of one or more phospholipids of natural or synthetic origin that can be treated (eg, by using mild sonication) to form spherical vesicles in which the lipids form a bilayer. Such vesicles, surrounded by a lipid bilayer, are termed liposomes. 

The lipid content of the membranes can be varied, allowing systematic examination of the effects of varying lipid composition on certain functions. For instance, vesicles can be made that are composed solely of phosphatidylchohne or, alternatively, of known mixtures of different phospholipids, glycohpids, and cholesterol. The fatty acid moieties of the lipids used can also be varied by employing synthetic lipids of known... 

Liposomes — These are synthetic lipid vesicles consisting of one or more phospholipid bilayers they resemble cell membranes and can incorporate various active molecules. Liposomes are spherical, range in size from 0.1 to 500 pm, and are thermodynamically unstable. They are built from hydrated thin lipid films that become fluid and form spontaneously multilameUar vesicles (MLVs). Using soni-cation, freeze-thaw cycles, or mechanical energy (extrusion), MLVs are converted to small unilamellar vesicles (SUVs) with diameters in the range of 15 to 50 nm. ... 

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