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DC Field | Value | Language |
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dc.contributor.advisor | Berti, Paul | - |
dc.contributor.advisor | Capretta, Fred | - |
dc.contributor.author | Gawuga, Vivian | - |
dc.date.accessioned | 2017-06-13T14:45:50Z | - |
dc.date.available | 2017-06-13T14:45:50Z | - |
dc.date.issued | 2008-10 | - |
dc.identifier.uri | http://hdl.handle.net/11375/21598 | - |
dc.description.abstract | The emergence of antibiotic resistance to current treatments of bacterial infection represents a major challenge that needs to be addressed with the development of new generations of inhibitors. The enzyme 5-enolpyruvylshikimate 3- phosphate synthase (EPSPS) catalyses the sixth step in the shikimate biosynthetic pathway, which is essential for the synthesis of aromatic compounds such as the aromatic amino acids phenylalanine, tryptophan and tyrosine. It occurs in plants, bacteria and some parasites. Since the pathway is absent in mammals but essential for the pathogenicity of a number of organisms, EPSPS is considered a prospective target for new inhibiter design. A number of EPSPS inhibitors have been reported in the literature. What we are lacking is an understanding of the features that are important for binding EPSPS. We have synthesized compounds to probe the active site of the enzyme based on the knowledge of an enzyme-catalyzed intermediate with a high cationic character. This will include assembling bipartite/tripartite inhibitors to discover what interactions or structural motifs are important for binding. Once the features important for binding to EPSPS are understood, the possibility of elaborating them to create potent inhibitors of EPSPS will be investigated. In addition, the synthesis of two shikimate analogs [5-^(18)O] shikimic acid and 4-deoxyshikimic acid were completed for further experiments to probe the enzyme mechanism in detail, and for transition state structure by transition state analysis. Transition state analysis using kinetic isotopic effects (KIE) will elucidate the transition state structure of the enzyme-catalyzed EPSP reaction, and provide a detailed starting point for designing EPSPS inhibitors. | en_US |
dc.language.iso | en | en_US |
dc.subject | design | en_US |
dc.subject | synthesis | en_US |
dc.subject | inhibitors | en_US |
dc.subject | enolpyruvyl | en_US |
dc.subject | shikimate | en_US |
dc.subject | 3-phosphate | en_US |
dc.title | Design and synthesis of potential inhibitors of enolpyruvyl shikimate 3-phosphate synthase (EPSPS) | en_US |
dc.contributor.department | Chemistry | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
Appears in Collections: | Digitized Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Gawuga_Vivian_2008Sept_Masters.pdf | 3.13 MB | Adobe PDF | View/Open |
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