Aqueous interfaces peptides

Chipot C. and Pohoriiie A. Structure and dynamics of small peptides at aqueous interfaces - a multi-nanosecond molecular dynamics study. Theochem.-J. Mol. Str. 

Liposomes are microstructures composed of one or more concentric spheres of (phospho)lipid bilayer, separated by water or aqueous buffer compartments. Those particles can encapsulate and dehver both hydrophilic and lipophilic substances. Water soluble substances can be entrapped in the central aqueous core, lipid soluble substances in the membrane and peptide and small proteins at the hquid aqueous interface. The size of such a particle can differ from 20 nm to 10 pm. Liposomes are in general made synthetically e.g. by the lipid hydration method. Liposomal medicines are on the market for the treatment of systemic fungal infections, tumours and for vaccination. 

This is another example of the hydrophobic effect which is manifested for peptides at aqueous interfaces as a tendency to segregate polar and nonpolar side chains into the aqueous and nonpolar phases, respectively. 

The characteristic coiled-coil motifs found in proteins share an (abcdefg) heptad repeat of polar and nonpolar amino acid residues (Fig. 1). In this motif, positions a, d, e, and g are responsible for directing the dimer interface, whereas positions b, c, and f are exposed on the surfaces of coiled-coil assemblies. Positions a and d are usually occupied by hydrophobic residues responsible for interhelical hydrophobic interactions. Tailoring positions a, d, e, and g facilitates responsiveness to environmental conditions. Two or more a-helix peptides can self-assemble with one another and exclude hydrophobic regions from the aqueous environment [74]. Seven-helix coiled-coil geometries have also been demonstrated [75]. 

Considering only the lipid phase as the transport pathway for the peptide, as the solute enters and diffuses across the membrane it will encounter a number of different microenvironments. The first is the aqueous membrane interface (Fig. 23). In this region, the hydrated polar headgroups of the membrane phospholipids separate the aqueous phase from the apolar membrane interior. It has been shown that this region is capable of satisfying up to 70% of the hydrophobic effect... 

Desfosses et al. [328] measured binding of oxyphenyl betazone to the N-ter-minal peptic fragment of human serum albumin (HSA) in aqueous buffer and AOT/isooctane-RMs. The peptide affinity for the drug did not decrease in RMs. The interactions of HSA at membrane mimetic interface and its subsequent unfolding was suggested to constitute a drug release facilitating mechanism. 

Specific formulation strategies need to be employed for macromolecule compounds. An excellent review of protein stability in aqueous solutions has been published by Chi et al. (92). In addition to solution stability of proteins and peptides, aerosolization may result in significant surface interfacial destabilization of these compounds if no additional stabilization excipients are added. This is due to the fact that protein molecules are also surface active and adsorb at interfaces. The surface tension forces at interfaces perturb protein structure and often result in aggregation (92). Surfactants inhibit interface-induced aggregation by limiting the extent of protein adsorption (92). 

The high molar mass species reside mostly in the aqueous phase with a number of peptide groups residing in the oil/water interface [293]. Although these latter surfactants are less effective at reducing interfacial tension, they can form a viscoelastic membrane-like film around oil droplets or air bubbles. These tend to be used in the preparation of, for example, O/W emulsions. These trends are by no means exclusive, mixtures are the norm and competitive adsorption is prevalent. Caseinate, one of the most commonly used surfactants in the food industry, is itself a mixture of interacting proteins of varying surface activity [814],... 

The arrangement of the proteins within the membrane seems to depend to some extent on the electrostatic surface potential and interface permittivity. It is influenced by electrostatic interaction between the proteins, polar head groups of the phospholipid and ions within the aqueous medium of the membrane surface. This can be affected by exogenous molecules such as drugs. Phospholipid-induced conformational change in intestinal calcium-binding protein in the absence and presence of Ca2+ has been described [37]. There is, however, no doubt that hydrophobic interactions between peptides and membrane interfaces play an important role. A general frame-... 

Fig. 4. Schematic illustration of how hydrophobic periodicity can influence secondary structure formation. In this illustration, the closed circles symbolize apolar residues and open circles symbolize polar residues. In dilute, aqueous solution, the peptides lack a single defined conformation. However, in the presence of an apolar-water interface, they adopt a secondary structure that maximizes the interactions of the apolar groups with the apolar medium and the polar groups with water. Taken from DeGrado and Lear (1985).

Tonegawa et al. (2004) created a cationic polylysine with a tetrapeptide end sequence (glycine-tyrosine-glycine-lysine), which is a motif common to the consensus sequences of mussel adhesive proteins. They then cross-linked this with the anionic polysaccharide, gellan, enzymatically. The polyionic complexation between the cationic peptide and the anionic polysaccharide formed a hybrid fiber at the aqueous solution interface that, when cross-linked, mimicked the byssus gel that marine mussels use to adhere to surfaces, despite the presence of water and salt. 

Other IRRAS applications to peptides and proteins. In addition to the pulmonary surfactant system, a variety of other applications employing IRRAS to study peptide and protein conformation and orientation have appeared. The secondary structure conversion of the amyloid (prion)-protein in the normal form into the abnormal form is the main cause of several human and animal diseases, such as Alzheimer s disease [68]. The secondary structure of the first 40 residues of the amyloid protein was detected by circular dichroism (CD) in aqueous solution and with IRRAS at the interface. A stable /1-sheet-enriched state of the amyloid is formed at the air-water interface, in contrast to the initial bulk solution containing high a-helix/random coil and low /l-sheet parts. The change in the pH going from bulk (alkaline pH) to the interface (neutral or slightly acidic pH) can have effects on the conformation at the interface. Another alternative might be the intrinsic hydrophobicity of the air-water interface, which is a hydrophobic-hydrophilic system with air as the hydrophobic part. 

As schematically own in Fig. 30, the cell membranes of living organism (/ S6) are composed of a lipid bilayer and form the interface between the intracellular and the extracellular aqueous parts. Concentrations of metal ions and amino adds in the cell are thus kept constant and the biological functions in the cell are executed. Specifically, the concentration of metal ions is in a dynamic equilibrium between the inside and the outside of the cell membrane, and it has been suggested that the mass tran rt through the membrane is mediated by lipoproteins. For the metal-km tran rt through the membrane, the participation of a group of cyclic conqxrunds called lonophores is important, which is dosely related to the antibiotic actions of cyclic peptides and cyclic depsipeptides (iJ6). These cyclic compounds are compatibile... 

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