Membranes model membrane solvent systems

A CRO may also allow for the in-house introduction of specialized lipophilic scales by transferring routine measurements. While the octanol-water scale is widely applied, it may be advantageous to utilize alternative scales for specific QSAR models. Solvent systems such as alkane or chloroform and biomimetic stationary phases on HPLC columns have both been advocated. Seydel [65] recently reviewed the suitabihty of various systems to describe partitioning into membranes. Through several examples, he concludes that drug-membrane interaction as it relates to transport, distribution and efficacy cannot be well characterized by partition coefficients in bulk solvents alone, including octanol. However, octanol-water partition coefficients will persist in valuable databases and decades of QSAR studies. 

To study the structural behaviour of MAPs, an adequate membrane model (see Fig. 5) is essential. Simple organic solvent systems, such as DMSO, MeOH/H20 or TFE/PLO mixtures, present a similar dielectric environment as a membrane on... 

In a very thoughtful investigation of solvent systems to model membrane characteristics, Leahy et al. (1989, 1992) have argued that two receptors sited in different tissues (or membranes) could exist in environments that are very different in hydrogen bonding character one may be surrounded by amphiprotic groups (as in a protein) or by proton donors the other may be surrounded by proton acceptors (as in a phospholipid membrane). 

Photosynthetic model systems have recently been exhaustively reviewed elsewhere [5, 6, 218] and a number of results are given in the latest literature [219-224]. The attention of the researchers is focused on topics such as electron-transfer chain and energy dissipation within models (the first step is the transfer of an electron from a metallotetrapyrrole moiety yielding a cation radical) the dependences of the electron-transfer rate constant on the driving force of the process distance and mutual orientation of donor and acceptor sites influences of membranes and medium (solvent) properties, etc. 

We first screened about 2000 solvent systems for their ability to solubilize polyAla, polyPhe, polyLeu, and gramicidin. Admittedly, none of these polypeptides can be regarded as particularly good models for natural biotopic membrane proteins (especially polyLeu). However, it was reasoned that solvent systems which were successful in solubilizing these peptides would likely prove effective in solubilizing more conventional membrane proteins. The following neat solvents formed the basis for the various mixtures tested. 

These experiments have not demonstrated that the conformational preferences of signal sequences are important to their ability to export proteins. To address this problem, we synthesized the family of E. coli K-receptor protein wild-type and mutant signal sequences (shown in Fig. 5 and described in Section III,H) and determined their conformations in various polar and apolar environments by CD (Briggs and Gierasch, 1984 Briggs, 1986). The solvents for these experiments included aqueous buffer and TFE, as described above. In addition, sodium dodecyl sulfate (SDS) micelles and phospholipid vesicles were used as membrane model systems. 

Twist JN, Zatz JL. Membrane-solvent-solute interaction in a model permeation system. J Pharm Sci 1988 Jun 77(6) 536-540. 

Both aqueous organic solvent mixtures and differently charged micelles can mimic only roughly the environment of natural cell membranes. In order to analyze in more appropriate model systems possible interactions of gastrin and CCK with cell membranes and to determine their conformational states in lipid bilayers, we have recently investigated in detailed manner this aspect using liposomes. The similarity betwen liposomes and natural membranes is extensively exploited both in vitro and in vivo because of the ability of liposomes to mimic the behaviour of natural membranes. Moreover, the value of liposomes as model membrane systems derives from the fact that they can be constructed with natural constituents. In our approach, we selected as model membranes those formed with the zwitterionic lipids di-myristoylphosphatidylcholine (DMPC) and di-palmitoylphosphatidylcholine (DPPC) as these lipids constitute the major components of most cell membranes. Moreover, in order to operate with a simple system, small unilamellar vesicles (SUVs) were used, i.e. with a diameter between 25 and 250 nm as resulting by rod-type sonication or by extrusion (51). 

Membrane environment. Membranes are large structures, translocation of molecular structures through membranes may involve significant conformational changes, and so these systems are natural candidates for implicit solvent modeling. One of the challenges here is accurate and computationally facile representation of the complex dielectric environment that, in the case of membranes, includes solvent, solute, and the membrane, all with different dielectric properties. Corrections to the GB model have been introduced [45-47] to account for the effects of variable dielectric environment. Other implicit membrane models, not based on the GB, have also been proposed [48]. 

Overton and Meyer both used olive oil as a partitioning system to model the physicochemical properties of the putative membrane lipoid site of action. Although Overton attempted to use melted cholesterol and other substances he thought might serve as a better reference phase, he abandoned this approach due to problems with the formation of inseparable emulsions (31). Collander in Finland (65) experimented with a variety of aqueous organic solvent systems and found that for many simple nonelectrolytes, the values were well-correlated according to the following equation ... 

Bhanushali, D., Kloos, S., Kurth, C., and Bhattacharyya, D. (2001) Performance of solvent-resistant membranes for non-aqueous systems Solvent permeation results and modeling. Journal of Membrane Science 189, 1-21. 

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