Thesis (M. Phil.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 75-82).

Würzburg, Univ., Diss., 2009. / Zsfassung in dt. Sprache.

Thesis (Ph. D.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains v, 129 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 118-129).

Techn. Universiẗat, Diss., 2006--München.

Thèse (M.Sc.)--Université Laval et Université du Québec à Chicoutimi, 2004. / Bibliogr.: f. 130-136. Webographie: f. 137. Publié aussi en version électronique.

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2006. / Includes bibliographical references (leaves 96-103). Also available in electronic version.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

Quinolinate phosphoribosyltransferase (QPRTase, E.C. 2.4.2.19) is considered to be a unique enzyme in that it is thought to catalyse two distinct chemical reactions. Both the transfer of a phosphoribosyl group from 5-phosphoribosyl-1- pyrophosphate onto the nitrogen of quinolinic acid and the subsequent decarboxylation of the intermediate to form nicotinic acid mononucleotide are thought to be catalysed by the QPRTase system. Analogues of quinolinic acid were designed as potential inhibitors of QPRTase. These contain acidic groups at the 2- and 3- positions but are unable to decarboxylate. However, such compounds may be able to undergo the phosphoribosyl transfer reaction, potentially increasing their inhibitory potency. These compounds may be useful as "biological tools" allowing the neurological effects of an increase in quinolinic acid levels to be investigated. The compounds may show anti-fungal activity blocking the kynurenine pathway for NAD production. 2-Sulfonicotinic acid was synthesised by the oxidation of 2-mercaptonicotinic acid by either basic potassium permanganate, or iodine, with the structure was confirmed by X-ray crystallography. In biological testing the acid was shown to be neither an agonist nor antagonist of the NMDA receptor, or to be neurotoxic. A number of synthetic routes towards 2-phosphononicotinic acid, an alternative quinolinic acid analogue, were attempted though none were successful. These included orthometallation strategies and palladium coupling reactions to incorporate the phosphonic acid group at the 2- position. Nucleophilic addition routes, methods of building up the pyridine ring and including non-selective phosphonic acid addition were also examined. However, a related derivative, 2-(phosphonomethyl)nicotinic acid, was successfully synthesised. The non-enzymic decarboxylation of N-alkyl quinolinic acids was investigated, for comparison with the decarboxylation reaction catalysed by QPRTase. Both N- methyl and N-ethylquinolinic acid were synthesised, and the pH versus rate profiles measured. The rate maximum for both compounds was at pH 1.5, with the rate decreasing both above and below the maximum. N-Methylquinolinic acid was 10 times faster than quinolinic acid itself, demonstrating the effect of the nitrogen substituent. The N-ethyl derivative decarboxylated a further 1.5 times faster, showing the effect of increasing the size of the substituent. An Arrhenius plot was also carried out, giving an activation energy for the reaction of 153 kJ mol-1. Attempts to prepare the N-propyl derivative were unsuccessful, as decarboxylation occurred very readily to give N- propylnicotinic acid.

Chlamydia are Gram negative, obligate intracellular bacterial pathogens responsible for diseases that affect both animals and humans. Only two vaccines have been developed for Chlamydia, targeting C. felis and C. abortus, and development of antibiotic resistance and/or persistent infection forms has been documented for multiple species. Consequently, identification of new therapeutic targets is critical for prevention and treatment of chlamydial infections. These bacterial pathogens have a unique biphasic developmental cycle beginning with the infectious and environmentally stable elementary body, which enters a host cell and envelopes itself in the host membrane forming an inclusion. While residing in the inclusion, the EB transitions into the metabolically active and replicative reticulate body. The RB divides by binary fission before converting back into the EB and exiting the host cell by inclusion extrusion or cell lysis. The signals that initiate morphogenesis and the mechanism(s) mediating the transition between EB and RB forms are poorly understood. Eukaryote-like serine/threonine kinases (Hank’s type kinases) have recently been described to play major roles in cellular development and pathogenicity in prokaryotes. Chlamydia encode three Hank’s type kinase; Pkn1, PknD, and Pkn5. We hypothesize that these kinases control bacterial differentiation and metabolism by regulating protein activity via phosphorylation, making them potential targets for anti-chlamydial therapeutics. To aid in future efforts to elucidate the roles of these Hank’s type kinases in the physiology of C. trachomatis, my thesis developed protocols for the affinity purification of recombinant Pkn1 and Pkn5 and assessed the efficacy of a high-throughput kinase assay for Pkn1.