Amino acid sidechains

The is-olefin was prepared as a trans-amide bond replacement. A number of compounds incorporating substituents to mimic both natural and unnatural amino acid sidechains were prepared by adapting chemistry developed by Ibuka for the synthesis of Zs-olefin peptide isosteres (see Scheme l).40,41 The key step involved anti-SN2 displacement of vinyl mesylate 8 by boron trifluoride-activated cuprate addition. Compounds containing butyl, propyl, and benzyl substituents at the allylic positions to mimic the aj and sidechains produced potent FTase inhibitors (Table 4). 

All the constituent amino acid sidechains in proteins are susceptible to attack by oxidants and free radicals, but some are more vulnerable than others. Thus, exposure of proteins to free radical-generating systems may induce tertiary structural changes as a consequence of modifications to individual amino acid sidechains. As secondary structure is stabilised by hydrogen bonding between peptide groups, interactions of radical species with the polypeptide backbone and interference with the functional groups of the peptide bonds may cause secondary structural modifications. Disruption of the secondary structure may also occur under certain conditions of free radical attack at the a-carbon atom of the peptide bond [20],... 

Through their lipophilic nature the aldehyde lipid peroxidation products remain associated with the LDL particle, diffuse to the apoB and react there with amino-acid sidechains (for example epsilon amino groups of lysine). 

Figure 12.1 shows the molecular interaction fields produced by the hydrogen probe interacting with the amino acid sidechains inside the active site cavities of the cytochromes. Such MIFs are important in evaluating the available volume in the active site cavities, and the shape of these cavities. 

Table 11,3 Relative hydrophobic character of amino acid sidechains (Gly = 0) ...

The calculation of the energy matrix is a double loop over the two amino acids i j in Eq. (7.1). To facilitate the construction of alternate amino acid types and ro-tamers, we introduce two giant amino acids, which each have 18 amino acid sidechains, corresponding to all possible types except glycine and proline (which have no sidechain Fig. 7.1). The loop structure is the following ... 

Anderson DP (2004) BOINC a system for public-resource computing and storage. In 5th IEEE/ACM international workshop on grid computing. IEEE Comput Soc, Los Alamitos Janin J, Wodak S, Levitt M, Maigret B (1978) Conformation of amino acid sidechains in proteins. J Mol Biol 125 357-386... 

Stochastic dynamics has been found to be particularly useful for introducing simplified descriptions of the internal motions of complex systems. When applied to small systems (e.g., a peptide or an amino acid sidechain) it is possible to do simulations that extend into the microsecond range, where many important phenomena occur. Simulation studies using this method have been carried out, for example, to explore solvent effects on the dynamics of internal soft degrees of freedom in small biopolymers, e.g., the dynamics of dihedral angle rotations in the alanine dipeptide (see Chapt. IX.B.l). 

For some problems, such as the motion of heavy particles in aqueous solvent (e.g., conformational transitions of exposed amino acid sidechains, the diffusional encounter of an enzyme-substrate pair), either inertial effects are unimportant or specific details of the dynamics are not of interest e.g., the solvent damping is so large that inertial memory is lost in a very short time. The relevant approximate equation of motion that is applicable to these cases is called the Brownian equation of motion,... 

It is clear from this simple example that water can have a profound influence on conformational equilibria of small peptides. Corresponding effects are expected for other solvated biomolecules and individual exposed amino acid sidechains. The integral equation method is likely to be very useful in studying the effects of solvation on the conformational states of small drug and substrate molecules and to provide insights into the role of flexibility on the binding affinity of ligands.26 ... 

Figure 2. —Continued. Flow chart of the protocol used to synthesize tetrameric bundles of defined amino acid sequence. (I) HF cleavage releases the synthetic protein from the support and deprotects the amino acid sidechains. (]) Chromatography using HPLC generates the purified channel proteins.

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