Branched hydrophobic side chains

Branched hydrophobic side chains dominate the core of oi/p barrels... 

The packing interactions between a helices and p strands are dominated by the residues Val (V), He (I), and Leu (L), which have branched hydrophobic side chains. This is reflected in the amino acid composition these three amino acids comprise approximately 40% of the residues of the P strands in parallel P sheets. The important role that these residues play in packing a helices against P sheets is particularly obvious in a/P-barrel structures, as shown in Table 4.1. 

The principal polyphosphazenes that have been used in hydrogels are those with linear or branched ethyleneoxy side chains, aryloxy groups with carboxylic acid substituents, or mixed-substituent polymers that bear hydrophilic methylamino side groups plus a hydrophobic cosubstituent such as phenoxy or trifluoroethoxy. Cross-linking is usually accomplished by gamma-ray irradiation or, in the case of the carboxylic acid functional species, by treatment with a di- or tri-valent cation. Here, we will consider another example based on MEEP (3.79), a polymer that is well suited to the clean method of radiation cross-linking. 

Nonpolar and branched, the side chain of lie is involved in hydrophobic interaction which stabilizes the protein conformation. 

The dienophile must be a five-membered maleimidyl ring with an unsubstituted reactive double bond. Substituents would again collide with the walls of the catalytic pocket. A hydrophobic side chain (alkyl or aryl) makes a major contribution to RNA binding. Branching is not allowed at the alpha position (next to the maleimide ring), due to steric clash with the walls. The ribozyme distinguishes between different enantiomers of chiral substrates and accelerates cycloadditions with both enantio- and diastereoselectivity. 

Valine, leucine and isoleucine have branched hydrocarbon side chains which are unreactive and hydrophobic. Phenylalanine has a bulky aromatic side chain and this too is hydrophobic. As a result of their water-repellant properties these amino acids tend to orientate towards the interior of folded polypeptide chains. 

The polymyxins are a group of closely related lipopeptide antibiotics produced by B. polymyxa and related bacilli. As seen in O Fig. 10.5, polymyxin B is a decapeptide in which amino acids 3 through 10 form a cyclic octapeptide. A branched-chain fatty acid is connected to the terminal 2,4-diaminobutyric acid (DAB). The structures of polymyxins differ in substituents at residues 3 (DAB or D-Ser), 6 (o-Leu or L-Ileu), or 7 (d- or l-DAB) (Suzuki et al. 1965). The cationic 7y-amino groups of the DAB residues, together with the hydrophobic side chain of the fatty acid, give these antibiotics the surface-active properties of a cationic detergent. Pseudomonas strains produce viscosin, a peptidolipid biosurfactant which lowers surface tension of water to 27 mN/m (Neu et al. 1992). 

As noted by the original authors (Dorovska et al., 1972), and cited by Fersht (1985), there is an excellent linear correlation between log/ccat/KM and the Hansch hydrophobicity parameters (v) of the side chains (Fig. 9, A), except for the two branched side chains (valine and isoleucine residues). However, since the ku values for the esters do vary somewhat (Table A6.8), the values of pKrs do not correlate as strongly with ir (Fig. 9, B). Moreover, the plot shows distinct curvature which probably indicates the onset of a saturation effect due to the physical limits of the Sj binding pocket, adjacent to the enzyme s active site. Still, the points for valine and isoleucine deviate below the others, suggesting that the pocket has a relatively narrow opening. 

The presence of bulky, (3-branched side chains can be helix promoting or destabilizing depending on the environment. 100 The role of hydrophobic residues in helix stabilization has been studied in Ala-based peptides 106 as well as through Monte Carlo calculations. 107 The positioning of hydrophobic residues is also important. In amphiphilic helices, hydrophobic residues repeat approximately every three to four residues, such that one side of the helix is hydrophilic and one side hydrophobic. The amphiphilicity makes the peptide susceptible to helix formation in the presence of lipid-water interfaces. 108 109 ... 

The enzyme triosephosphate isomerase, abbreviated to TIM, was found to have an important type of structure, now called an a//3 or TIM barrel, consisting of at least 200 residues. In its idealized form, the barrel consists of eight parallel /3 strands connected by eight helixes (Figure 1.19). The strands form the staves of the barrel while the helixes are on the outside and are also parallel (Figure 1.20). (3 strands 1 and 8 are adjacent and form hydrogen bonds with each other. The center of the barrel is a hydrophobic core composed of the side chains of alternate residues of the strands, primarily those of the branched... 

In fact, there are other considerations that complicate the compositional issue still further. The ad-variants bear a further optically active center as a result of the chain-branch position, which is likely to be racemic (it is adjacent to a carbonyl moiety). Because it is remote through space from other optical centers in a-acids and other optically active hop-derived components, it is unlikely to have a practical bearing on the properties and therefore the application of these compounds. More relevant though is the observation of minor components of the a-acids that have both shorter and longer side chains than the more abundant co-, n-, and ad-variants. Given that hydrophobicity is related to the potency of the brewing value of the hop-derived components, there is justification for the quantification of particularly the more hydrophobic species, as recently exemplified by Wilson et al. (18). 

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