Amphipathic side chains

In order for folded helices to assemble into tertiary structures in water, they need to be amphipathic (e.g. where one hehcal face is hydrophobic and the other is hydrophilic). Because the first hehcal peptoids contained very hydrophobic chiral residues, ways to increase the water solubihty and side-chain diversity of the hehx-indudng residues were investigated [49]. It was found that a series of side chains with chiral-substituted carboxamides in place of the aromatic group could stiU favor hehx formation, while dramatically increasing water solubility. 

It seems that for drugs to cause accumulation of phospholipids, the necessary physicochemical characteristic is the presence of both hydrophilic and lipophilic parts to the molecule, as exemplified by chlorphentermine (see chap. 3) (chap. 5, Fig. 1). They contain a hydrophobic ring structure and a hydrophilic side chain with a positively charged (cationic) amine group. Such molecules are known as cationic amphipathic drugs or CADs. Other drugs, all in use, known to cause phospholipidosis are amiodarone, chloroquine (chap. 5, Fig. 1), tafenoquine, and gentamycin. 

Names, structural char acteristics, and func tions of bile acids The primary bile acids, cholic or chenodeoxycholic acids, contain two or three alcohol groups, respectively. Both have a shortened side chain that terminates in a carboxyl group. These structures are amphipathic, and can serve as emulsifying agents. 

In current structural. models of the Na+ channel, the four homologous a-helix domains pack together around a central pore formed by the four copies of the amphipathic helix 3. These helices probably are oriented so that most of their ionizable amino acid side chains face the aqueous space in the pore, whereas most of their nonpolar side chains face outward and interact with hydrophobic residues of other helices (fig. SI.7). The diameter of such a pore is... 

Shown in the upper panel of Scheme 2 is the top view of the GS14 backbone showing the positions of potential H-bonds (dashed lines) in each five-residue p-strand and the two type II p-turns defined by the D-Tyr-Pro sequence which link the two P-strands. The side view of GS14 (2) is shown in the lower panel of Scheme 2 where the P-sheet structure of the backbone is evident and the relative orientation of successive side chains within the 3-strands can be seen. The P-sheet structure gives GS14 (2) a highly amphipathic nature with a large hydrophobic face made up of Val and Leu residues and a basic face made up of Lys residues. 

Poly(ethylene oxide) (PEO) macromonomers constitute a new class of surface active monomers which give, by emulsifier-free emulsion polymerization or copolymerization, stable polymer dispersions and comb-like materials with very interesting properties due to the exceptional properties of ethylene oxide (EO) side chains. They are a basis for a number of various applications which take advantage of the binding properties of PEO [39], its hydrophilic and amphipathic behavior [40], as well as its bio compatibility and non-absorbing character towards proteins [41]. Various types of PEO macromonomers have been proposed and among them the most popular are the acrylates and methacrylates [42]. 

As the o-helix has 3.6 residues per turn, hydrophobic side chains spaced at combinations of three and four residues apart are required to make an amphipathic structure. For helices in globular proteins, a variety of combinations of three-plus-four spacings of hydrophobic residues are observed (Chothia et al., 1981). This leads to a range of helix-helix packing angles and arrangements. However, to form more persistent fibrous coiled-coil... 

Hydrophobic forces The hydrophobic effect is the name given to those forces that cause nonpolar molecules to minimize their contact with water. This is clearly seen with amphipathic molecules such as lipids and detergents which form micelles in aqueous solution (see Topic El). Proteins, too, find a conformation in which their nonpolar side chains are largely out of contact with the aqueous solvent, and thus hydrophobic forces are an important determinant of protein structure, folding and stability. In proteins, the effects of hydrophobic forces are often termed hydrophobic bonding, to indicate the specific nature of protein folding under the influence of the hydrophobic effect. 

The top side of the helix contains only hydrophobic side chains, while the other surfaces are polar or charged this is an amphipathic helix. As an integral membrane protein, it is likely to dip its hydrophobic surface into the lipid bilayer but expose the other surfaces to the aqueous phase. An alternative arrangement might be to cluster, say, 10 helices, one from each of 10 subunits, around a central hydrophilic core, while exposing only the hydrophobic surface to the lipid bilayer. 

Because cholesterol contains an -OH group, it is amphipathic. It controls membrane fluidity in mammals by inhibiting the ordering of fatty acid side chains, but it is absent from bacterial plasma membranes. 

In order to adsorb at the interface and be surface-active, proteins must be flexible and amphipathic (i.e., have some affinity for both phases). The hydrophobic side-chains will adsorb on the oil side of the interface while the hydrophilic side-chains will interact with the aqueous phase. Three aspects of the side-chains of a protein are important ... 

Using the hydrophobicity scale as an example, the amino acid residues can be represented by the real-numbered scalar value. They can also be classified with respect to their side chains as polar, nonpolar, or amphipathic, depending on the range of the hydrophobicity in the scale, such as in... 

For proteins with multiple transmembrane domains, it is not necessary to have exclusively hydrophobic amino acids a pair of amino acids with opposite charges may be present in the lipophilic environment of the membrane. Therefore a search for amphipathic a-helices must be undertaken. Amphipathic helices have well-defined hydrophobic character, the hydrophobic face which would project towards the membrane/lipid environment, and a hydrophilic face, which would project out into the aqueous phase or towards the core of a helix bundle. Often times the distinction is not clear and there are regions of mixed hydrophobic/hydrophilic character. Graphically this can be realized with a helical-wheel representation in which the amino acid side chains project out, at 100 degree intervals, from the view along the long, helical axis. 

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