dc.contributor.author | Ampaw, Anna A. | |
dc.date.accessioned | 2018-02-12T17:13:17Z | |
dc.date.available | 2018-02-12T17:13:17Z | |
dc.date.issued | 2018-02-12T17:13:17Z | |
dc.identifier.uri | http://hdl.handle.net/10222/73603 | |
dc.description.abstract | β-Phosphoglucomutase (βPGM) is an isomerase that catalyzes the conversion of β-glucose 1-phosphate to glucose 6-phosphate via a 1,6-bisphosphate intermediate. Incorporation of 5-fluorotryptophan (5FW) into βPGM (ie. 5FWβPGM) as a 19F NMR spectroscopic probe revealed that the 19F nucleus in 5FW is a sensitive probe for monitoring metal fluoride transition state analogue (TSA) complexation and ligand binding. The ability of βPGM to form transition state analogue complexes with novel compounds, β-glucose 1,6C-phosphonate, and β-2-deoxy-2-fluoro glucose and mannose 1C-phosphonates were examined; however, only β-glucose 1,6C-phosphonate (IC50 = 186 +/- 73 µM) and β-2-deoxy-2-fluoro glucose (2.68 +/- 0.04 µM) configured analogs bound to βPGM. All compounds that exhibited complexation with 5FWβPGM by 19F NMR spectroscopy were confirmed as competitive. Approaches to the synthesis of 1,6-bisphosphate and phosphofluoridates analogs as mechanism-based inactivators of 5FWβPGM are described. | en_US |
dc.language.iso | en | en_US |
dc.subject | Organic Chemistry | en_US |
dc.subject | Enzymology | en_US |
dc.subject | Enzyme kinetics | en_US |
dc.subject | Nuclear magnetic resonance (NMR) | en_US |
dc.title | The Expression of 19F-Labeled Beta-Phosphoglucomutase and the Evaluation of Its Inhibitors | en_US |
dc.date.defence | 2016-07-28 | |
dc.contributor.department | Department of Chemistry | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | n/a | en_US |
dc.contributor.graduate-coordinator | Heather A. Andreas | en_US |
dc.contributor.thesis-reader | Bruce Grindley, Stephen Bearne | en_US |
dc.contributor.thesis-supervisor | David L. Jakeman | en_US |
dc.contributor.ethics-approval | Not Applicable | en_US |
dc.contributor.manuscripts | No | en_US |
dc.contributor.copyright-release | Not Applicable | en_US |