Side chain analysis

Overall, the profile of the heterocyclic calcitriols is dependent on the nature of the heterocyde, the position of substitution and the length of the side-chain. Analysis of theobtained data led to thecondusion that butyl oxazole 28b (ZK191784) displayed the most promising partial agonistic profile which could potentially lead to tissue-selective activity. This compound was therefore selected to be characterized more intensively in vitro and in vivo. 

Tiers N L, W D Carlson and M Karplus 1987 Analysis of Side-Chain Orientations in Homologous Proteins. Journal of Molecular Biology 196 175-198. 

Analysis Using the branch-point, in the largest side chain as a guide, we can put in a hydroxyl group (as in frame 72). 

Analysis The one functional group is something of a red herring since we shall put in the acetyl side chain by a Friedel-Crafts reaction on the real target molecule, 399A ... 

Structure of xanthan has been determined by chemical degradation and methylation analysis (335,336) it is composed of repeating units consisting of a main chain of D-glucopyranosyl residues with trisaccharide side chains made up of D-mannopyranosyl and D-glucopyranosyluronic acid residues. 

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

The side-chain chlorine contents of benzyl chloride, benzal chloride, and benzotrichlorides are determined by hydrolysis with methanolic sodium hydroxide followed by titration with silver nitrate. Total chlorine determination, including ring chlorine, is made by standard combustion methods (55). Several procedures for the gas chromatographic analysis of chlorotoluene mixtures have been described (56,57). Proton and nuclear magnetic resonance shifts, characteristic iafrared absorption bands, and principal mass spectral peaks have been summarized including sources of reference spectra (58). Procedures for measuring trace benzyl chloride ia air (59) and ia water (60) have been described. 

FI Schrauber, F Eisenhaber, P Argos. Rotamers To be or not to be An analysis of ammo acid side-chain conformations m globular proteins. J Mol Biol 230 592-612, 1993. 

MJ McGregor, SA Islam, MJE Sternberg. Analysis of the relationship between side-chain conformation and secondary structure m globular proteins. J Mol Biol 198 295-310, 1987. 

RB Russell, GJ Barton. Structural features can be unconserved m proteins with similar folds. An analysis of side-chain to side-chain contacts secondary structure and accessibility. J Mol Biol 244 332-350, 1994. 

Analysis and prediction of side-chain conformation have long been predicated on statistical analysis of data from protein structures. Early rotamer libraries [91-93] ignored backbone conformation and instead gave the proportions of side-chain rotamers for each of the 18 amino acids with side-chain dihedral degrees of freedom. In recent years, it has become possible to take account of the effect of the backbone conformation on the distribution of side-chain rotamers [28,94-96]. McGregor et al. [94] and Schrauber et al. [97] produced rotamer libraries based on secondary structure. Dunbrack and Karplus [95] instead examined the variation in rotamer distributions as a function of the backbone dihedrals ( ) and V /, later providing conformational analysis to justify this choice [96]. Dunbrack and Cohen [28] extended the analysis of protein side-chain conformation by using Bayesian statistics to derive the full backbone-dependent rotamer libraries at all... 

As an example of analysis of side-chain dihedral angles, the Bayesian analysis of methionine side-chain dihedrals is given in Table 3 for the ri = rotamers. In cases where there are a large number of data—for example, the (3, 3, 3) rotamer—the data and posterior distributions are essentially identical. These are normal distributions with the averages and standard variations given in the table. But in cases where there are few data. 

E Benedetti, G Morelh, G Nemethy, HA Scheraga. Statistical and energetic analysis of side-chain conformations m oligopeptides. Int J Peptide Pi otem Res 22 1-15, 1983. 

T4 lysozyme has two such cavities in the hydrophobic core of its a helical domain. From a careful analysis of the side chains that form the walls of the cavities and from building models of different possible mutations, it was found that the best mutations to make would be Leu 133-Phe for one cavity and Ala 129-Val for the other. These specific mutants were chosen because the new side chains were hydrophobic and large enough to fill the cavities without making too close contacts with surrounding atoms. 

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