Amino acid polar, hydrophilic

As another example of polarity effects on macromo-lecular structure, consider polypeptide chains, which usually contain a mixture of amino acids with hydrophilic and hydrophobic side chains. Enzymes fold into complex three-dimensional globular structures with hydrophobic residues located on the inside of the structure and hydrophilic residues located on the surface, where they can interact with water (fig. 1.12). 

The side chains of the remaining amino acids are polar. Because they are attracted to polar water molecules, they are said to be hydrophilic ("water-loving") amino acids. The hydrophilic side chains are often found on the surfaces of proteins. The polar amino acids can be subdivided into three classes. 

Hydrophilic (water-loving) and hydrophobic (water-fearing) refer to the polarity of the R groups. When the R group consists of a polar group, then the amino acid is hydrophilic. When the R group consists of a nonpolar group, then the amino acid is hydrophobic. 

Cosolvents ana Surfactants Many nonvolatile polar substances cannot be dissolved at moderate temperatures in nonpolar fluids such as CO9. Cosolvents (also called entrainers, modifiers, moderators) such as alcohols and acetone have been added to fluids to raise the solvent strength. The addition of only 2 mol % of the complexing agent tri-/i-butyl phosphate (TBP) to CO9 increases the solubility ofnydro-quinone by a factor of 250 due to Lewis acid-base interactions. Veiy recently, surfac tants have been used to form reverse micelles, microemulsions, and polymeric latexes in SCFs including CO9. These organized molecular assemblies can dissolve hydrophilic solutes and ionic species such as amino acids and even proteins. Examples of surfactant tails which interact favorably with CO9 include fluoroethers, fluoroacrylates, fluoroalkanes, propylene oxides, and siloxanes. 

Loop regions exposed to solvent are rich in charged and polar hydrophilic residues. This has been used in several prediction schemes, and it has proved possible to predict loop regions from an amino acid sequence with a higher degree of confidence than a helices or p strands, which is ironic since the loops have irregular structures. 

FIGURE 10.24 A helical wheel model of halorhodopsin. The amino acids facing the polar, hydrophilic core of the protein are shown. Of these 60 residues, 36 are conserved between halorhodopsin and bacteriorhodopsin. (Adapted from OesterMt, D., and Tittor, f, 1989. Treads ia Biochemical Scieaces 14 57—61.)... 

What about tertiary structure Why does any protein adopt the shape it does The forces that determine the tertiary structure of a protein are the same forces that act on ail molecules, regardless of size, to provide maximum stability. Particularly important are the hydrophilic (water-loving Section 2.13) interactions of the polar side chains on acidic or basic amino acids. Those acidic or basic amino acids with charged side chains tend to congregate on the exterior of the protein, where they can be solvated by water. Those amino acids with neutral, nonpolar side chains tend to congregate on the hydrocarbon-like interior of a protein molecule, away from the aqueous medium. 

Among the common amino acids, eleven have side chains that contain polar functional groups that can form hydrogen bonds, such as —OH, —NH2, and — CO2 H. These hydrophilic amino acids are commonly found on the outside of a protein, where their interactions with water molecules increase the solubility of the protein. The other nine amino acids have nonpolar hydrophobic side chains containing mostly carbon and hydrogen atoms. These amino acids are often tucked into the inside of a protein, away from the aqueous environment of the cell. 

Using liposomes made from phospholipids as models of membrane barriers, Chakrabarti and Deamer [417] characterized the permeabilities of several amino acids and simple ions. Phosphate, sodium and potassium ions displayed effective permeabilities 0.1-1.0 x 10 12 cm/s. Hydrophilic amino acids permeated membranes with coefficients 5.1-5.7 x 10 12 cm/s. More lipophilic amino acids indicated values of 250 -10 x 10-12 cm/s. The investigators proposed that the extremely low permeability rates observed for the polar molecules must be controlled by bilayer fluctuations and transient defects, rather than normal partitioning behavior and Born energy barriers. More recently, similar magnitude values of permeabilities were measured for a series of enkephalin peptides [418]. 

The cells of all contemporary living organisms are surrounded by cell membranes, which normally consist of a phospholipid bilayer, consisting of two layers of lipid molecules, into which various amounts of proteins are incorporated. The basis for the formation of mono- or bilayers is the physicochemical character of the molecules involved these are amphipathic (bifunctional) molecules, i.e., molecules which have both a polar and also a non-polar group of atoms. Examples are the amino acid phenylalanine (a) or the phospholipid phosphatidylcholine (b), which is important in membrane formation. In each case, the polar group leads to hydrophilic, and the non-polar group to hydrophobic character. 

There is another group of amino acids that contains relatively polar constituents and are thus hydrophilic in character. Asparagine, glutamine, threonine, and serine (Figure 1.5) are... 

Nucleotides, peptides, and amino acids also differ subtly in their polarities Some are more hydro-phobic than others. Thus, separation via reverse phase HPLC is possible. A reverse phase column, such as C18 or C8, has a low- to medium-polarity stationary phase. The more hydrophobic sample components interact to a greater degree with the stationary phase, and therefore elute more slowly than the more hydrophilic components. The sample elution order is from most hydrophilic to most hydrophobic. 

Since amino acids and nucleotides are all polar and hydrophilic, they will be eluted quickly by the column. The mobile phase (see below) is also selected on the basis of polarity, with a medium- to high-polarity solvent required. The opposite of reverse phase chromatography is normal phase, where the column packing is medium to high polarity and the mobile phase is nonpolar. This technology is generally not applied to the analysis of polar molecules such as amino acids or nucleotides. Some peptides are more hydrophobic, making this method potentially more useful for peptides than for amino acids or nucleotides. 

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