Hydrophilic amino acids

The extrinsic pathway of coagulation is activated when circulating factor VII encounters tissue factor. Tissue factor is a transmembrane glycoprotein, which is normally expressed by subendothelial fibroblast-like cells, which surround the blood vessel. An intact endothelium normally shields the circulating blood from exposure to tissue factor. The tissue factor molecule consists of a 219 amino acid hydrophilic extracellular domain, a 23 amino acid hydrophobic region that spans the membrane, and a 21 amino acid cytoplasmic tail that anchors the molecule to the cell membrane (15,16). Other sites of tissue factor expression include activated monocytes, activated endothelial cells, and atherosclerotic plaques. 

Fig. 9.6. Composite diagram showing the elution position of some peptides and amino acids. Chromatographic conditions column, Lichrosorb Si 60 7 fim (treated with 0.1 M copper(II) sulphate/1 M ammonia) mobile phase, (A) water/acetonitrile (10 90)-0.1 M ammonia, 1 ppm Cu " ", (B) water-acetonitrile (60 40)-0.95 M ammonia, 1 ppm Cu " ". Elution was achieved with a concave gradient of 0% B to 100% B over 70 min flow rate, 2 ml/min detection, UV at 254 nm. 1, Phe-Phe 2, Ala-Ala-Ala 3, mixture 4, Ala-Ser 5, Pro-Glu 6, Phe 7, Gly-Gly-Gly 8, Lys-Phe 9, Leu 10, Leu 11, Glu 12, Ala 13, Ser-Ser-Ser 14, Gly-His-Gly 15, Arg-Glu 16, Lys-Gly 17, Arg-Tyr 18, Pro-Gly-Lys-Ala-Arg,Lys-Lys-Gly-Glu A, hydrophobic, large peptides B, dipetides C, amino acids, hydrophilic peptides, basic peptides.

The monomeric unit of peptide-amphiphile (PA) is shown in Fig. 45.2. These PA have a long hydrophobic alkyl chain and a hydrophilic head group made of a sequence of various amino acids. Hydrophilic group is a bit bulkier than the hydrophobic group, thereby leading to the formation of cylindrical micelles. The four consecutive cysteine residues take part in the covalent capture of the self-assemble structure. Three glycine residues provide the head group flexibility, followed by the presence of a phosphorylated serine residue which binds with metal ions and further helps in the assembly. At the C-terminal... 

Fig. 1. The side chain R of the 20 standard amino acids +H3N—CHR—COO at pH 7. For proline, the complete stmcture is shown. Amino acid side chains can be categorized as aUphatic (Gly, Ala, Val, Leu, and He), hydrophilic (Ser, Thr, Asp, Glu, Asn, Gin, Lys, and Arg), sulfur-containing (Cys and...

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. 

The most common location for an a helix in a protein structure is along the outside of the protein, with one side of the helix facing the solution and the other side facing the hydrophobic interior of the protein. Therefore, with 3.6 residues per turn, there is a tendency for side chains to change from hydrophobic to hydrophilic with a periodicity of three to four residues. Although this trend can sometimes be seen in the amino acid sequence, it is not strong enough for reliable stmctural prediction by itself, because residues that face the solution can be hydrophobic and, furthermore, a helices can be either completely buried within the protein or completely exposed. Table 2.1 shows examples of the amino acid sequences of a totally buried, a partially buried, and a completely exposed a helix. 

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 3.6 Four-helix bundles frequently occur as domains in a proteins. The arrangement of the a helices is such that adjacent helices in the amino acid sequence are also adjacent in the three-dimensional structure. Some side chains from all four helices are buried in the middle of the bundle, where they form a hydrophobic core, (a) Schematic representation of the path of the polypeptide chain in a four-helrx-bundle domain. Red cylinders are a helices, (b) Schematic view of a projection down the bundle axis. Large circles represent the main chain of the a helices small circles are side chains. Green circles are the buried hydrophobic side chains red circles are side chains that are exposed on the surface of the bundle, which are mainly hydrophilic.

Lesk and Chothia did find, however, that there is a striking preferential conservation of the hydrophobic character of the amino acids at the 59 buried positions, but that no such conservation occurs at positions exposed on the surface of the molecule. With a few exceptions on the surface, hydrophobic residues have replaced hydrophilic ones and vice versa. However, the case of sickle-cell hemoglobin, which is described below, shows that a charge balance must be preserved to avoid hydrophobic patches on the surface. In summary, the evolutionary divergence of these nine globins has been constrained primarily by an almost absolute conservation of the hydro-phobicity of the residues buried in the helix-to-helix and helix-to-heme contacts. 

Since the outside of the barrel faces hydrophobic lipids of the membrane and the inside forms the solvent-exposed channel, one would expect the P strands to contain alternating hydrophobic and hydrophilic side chains. This requirement is not strict, however, because internal residues can be hydrophobic if they are in contact with hydrophobic residues from loop regions. The prediction of transmembrane p strands from amino acid sequences is therefore more difficult and less reliable than the prediction of transmembrane a helices. 

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.)... 

This ester was developed to impart greater hydrophilicity in C-terminal peptides that contain large hydrophobic amino acids, since the velocity of deprotection with enzymes often was reduced to nearly useless levels. Efficient cleavage is achieved with the lipase from R. niveus (pH 7, 37°, 16 h, H2O, acetone, 78-91% yield)... 

The 20 natural amino acids differ from each other by the nature of their sidechains. Differences involve overall size, hydrophobic or hydrophilic character and, perhaps most importantly, ionization state. While the sidechains are normally written in terms of neutral structures, some may also exist in either protonated or deprotonated forms depending on pH. 

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