Biochemistry and Pharmacology - Theses

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    Studies on β [beta]-glucans and β [beta]-glucoside hydrolases
    Clarke, Adrienne Elizabeth ( 1962)
    Investigations of the enzymes hydrolysing β-glucosidic linkages have been stimulated by interest in the hydrolysis of naturally occurring β-glucosides and β-glucans, and particularly in the last twenty years, by the appreciation of the economic significance of cellulose degradation. Enzyme systems hydrolysing β-glucosidic linkages have been found in animals, plants, fungi and bacteria. Fungi, in particular, produce a complex mixture of enzymes among which are a group of enzymes capable of hydrolysing β-glucosidic linkages. These β-glucoside hydrolases are presumably part of the equipment of the saprophytic forms for existence in a changing and competitive environment, and of the plant pathogens for penetration of the host cell wal.(Open document for complete abstract)
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    The effect of side chain complexity on the dimensions of polypeptide chains
    Paterson, Yvonne ( 1978)
    The aim of the work presented in this thesis was to examine the restrictions that the size of the side chain of an amino acid residue imposes on the total conformational (energy) space available to the adjacent peptide backbone. The conformational space of a series of N-acetyl-N'- methylamide derivatives of glycine, L-alanine, β-methyl-Lalanine, L-valine, β-methyl-L-valine and hydroxyethyl-L-glutamine was explored using empirical energy calculations with the most recently revised conformational energy parameters. Of the various regions of the total conformational space of the peptide backbone, the area surrounding the C eq 7 conformation I is the most favoured for all the residues studied, except the ones with the bulkiest (β-methyl-L-valine) and longest (hydroxyethy-L-glutamine) side chain. The steric constraints imposed by these two side chains favoured the extended backbone conformation. The preferred side chain conformations were predicted for those residues with multiple side chain rotameric states. L-Valine and β-methyl-L-alanine have only three side chain conformations, defined by the value of the variable side chain torsion angle X1; it was found that the trans rotameric state (x1 ≃ 180°) predominates for these residues. Hydroxyethyl- L-glutamine has seven side chain torsion angles which, using the rotational isomeric state model chosen for this study, generate 2,916 possible side chain conformations; however, one of these is overwhelmingly favoured (32%) and reasons for this preference are discussed. In the randomly coiled state the conformational energy space of single amino acid residues can be used to compute the unperturbed dimensions of a polypeptide chain since under these conditions short range interactions predominate. This provides a convenient method of assessing the accuracy of conformational energy calculations since their dimensions can also be derived experimentally. The unperturbed dimensions of homopolyamino acids composed solely of each residue featured in this study and also of copolypeptides of the type (hydroxyethyl- L-glutamine-X-X) n, where X = glycine, L-alanine or β-methyl-L-alanine were derived. In the course of the investigation the conditions under which the approximations inherent in this type of calculation are valid were rigorously established. The most accurate estimates of the characteristic ratios of the homopolymers of glycine, L-alanine, β-methyl-Lalanine, L-valine and hydroxyethyl-L-glutamine were 2.12, 8.06, 7.02, 9.21 and 9.75. The side chain of β-methyl-L-valine imposed profound steric restrictions on the backbone which resulted in a slowly converging characteristic ratio (94.8 at a chain length of 500 residues). The characteristic ratios of the copolypeptides (hydroxyethyl-L-glutamine-X-X) n, where X = glycine, L-alanine and β-methyl-L-alanine were 2.27, 8.56 and 7.73, respectively. Since hydroxyethyl-L-glutamine is a water solubilizing residue it should be possible to derive the characteristic ratios of copolypeptides of this type experimentally from their hydrodynamic behaviour in aqueous solution. In order to do this it is necessary to synthesize these copolypeptides which involves establishing a method for converting the side chain of glutamic acid to that of hydroxyethyl-L-glutamine. The conversion of poly-L-glutamic acid to polyhydroxyethyl-L-glutamine via its active N-hydroxysuccinimide ester and also by coupling the side chains to ethanolamine using a water soluble carbodiimide was explored. It was discovered that the carbodiimide could cleave peptide bonds in poly-L-glutamic acid and some of the features of this reaction and possible mechanisms for it were investigated.