dc.contributor.author | Gillis, Thomas | |
dc.date.accessioned | 2021-12-16T19:06:33Z | |
dc.date.available | 2021-12-16T19:06:33Z | |
dc.date.issued | 2021-12-16T19:06:33Z | |
dc.identifier.uri | http://hdl.handle.net/10222/81107 | |
dc.description.abstract | Cytidine-5′-triphosphate (CTP) synthase (CTPS) catalyzes the biosynthesis of CTP from UTP using either L-glutamine or free NH3 as a substrate. CTP is an essential precursor for viral replication; thus, its production has been targeted for the development of antiviral agents. With the advent of SARS-CoV-2, one approach for identifying therapies for COVID-19 is through the repurposing of existing antiviral drugs. To better understand potential off-target effects of repurposed antiviral agents, I analyzed the effects of vidarabine-5′-triphosphate (araATP), ribavirin-5′-triphosphate (RBVNTP), sofosbuvir-5′-triphosphate (STP), and N4-OH-CTP on Escherichia coli CTPS (ecCTPS) activity and filament formation. AraATP and STP were modest substrates for ecCTPS, while RBVNTP and N4-OH-CTP activated and inhibited ecCTPS, respectively. N4-OH-CTP induced filament formation by ecCTPS while STP prevented filament assembly. ATPγS was a substrate for ecCTPS and gemcitabine-5′-triphosphate inhibited both the wild-type and C268A ecCTPS variants to the same extent. Hence, repurposed antiviral drugs could affect intracellular CTP production. | en_US |
dc.language.iso | en | en_US |
dc.subject | Enzymes | en_US |
dc.title | EFFECTS OF 5′-TRIPHOSPHATE METABOLITES OF SPECIFIC ANTIVIRAL DRUGS ON CTP SYNTHASE ACTIVITY | en_US |
dc.type | Thesis | en_US |
dc.date.defence | 2021-12-08 | |
dc.contributor.department | Department of Biochemistry & Molecular Biology | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | n/a | en_US |
dc.contributor.graduate-coordinator | Dr. Barbara Karten | en_US |
dc.contributor.thesis-reader | Dr. David N. Langelaan | en_US |
dc.contributor.thesis-reader | Dr. Hyo-Sung Ro | en_US |
dc.contributor.thesis-reader | Dr. Catherine K.L. Too | en_US |
dc.contributor.thesis-supervisor | Dr. Stephen L Bearne | en_US |
dc.contributor.ethics-approval | Not Applicable | en_US |
dc.contributor.manuscripts | Not Applicable | en_US |
dc.contributor.copyright-release | Not Applicable | en_US |