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dc.contributor.authorLaourdakis, Christian Danielen_US
dc.date.accessioned2015-11-07T07:00:37Z
dc.date.available2015-11-07T07:00:37Z
dc.date.issued2014-05-15en_US
dc.identifier.othervt_gsexam:2409en_US
dc.identifier.urihttp://hdl.handle.net/10919/63987
dc.description.abstractMalaria is a parasitic infectious disease that results in millions of clinical cases per year and accounts for approximately 1 million deaths annually. Because the parasite has developed resistance to all current antimalarials, new therapies are urgently needed. Purine and pyrimidine biosynthesis for DNA and RNA synthesis has been recognized as a source of therapeutic targets. Targeted metabolite profiling has aided in the understanding of several biological processes in the parasite besides drug discovery. Therefore, having a robust analytical platform to quantify the purines and pyrimidines is of a great value. For this purpose an ion pair reversed phase ultra-performance liquid chromatography in tandem with mass spectrometry method was developed and validated. In addition, the apicoplast is an organelle present in the malaria parasite and other apicomplexan parasites. It was demonstrated that the apicoplast is essential for parasite's survival. The supply of isopentenyl diphosphate and dimethylallyl diphosphate for isoprenoid biosynthesis is the sole function of this organelle in the asexual intraerythrocytic stages. Isoprenoid precursors are synthesized through the methylerythritol phosphate (MEP) pathway in the malaria parasite while humans utilize the mevalonate pathway. Therefore, the MEP pathway is a source of drug targets for drug development. Our group has identified MMV008138 as anti-apicoplast inhibitor through phenotypic screening. Preliminary data suggest that the molecular target of MMV008138 may be within the MEP pathway. We used proteomic and metabolomic approaches to identify the molecular target of MMV008138 to aid future medicinal chemistry to improve the efficacy of this inhibitor.en_US
dc.format.mediumETDen_US
dc.publisherVirginia Techen_US
dc.rightsThis Item is protected by copyright and/or related rights. Some uses of this Item may be deemed fair and permitted by law even without permission from the rights holder(s), or the rights holder(s) may have licensed the work for use under certain conditions. For other uses you need to obtain permission from the rights holder(s).en_US
dc.subjectLC-MSen_US
dc.subjectDARTSen_US
dc.subjectPurines and Pyrimidinesen_US
dc.subjectPlasmodium falciparumen_US
dc.subjectNon-Mevalonate pathwayen_US
dc.titleMolecular target identification of antimalarial drugs using proteomic and metabolomic approachesen_US
dc.typeThesisen_US
dc.contributor.departmentBiochemistryen_US
dc.description.degreeMaster of Scienceen_US
thesis.degree.nameMaster of Scienceen_US
thesis.degree.levelmastersen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineBiochemistryen_US
dc.contributor.committeechairCassera, Maria Belenen_US
dc.contributor.committeememberMackey, Zachary Byronen_US
dc.contributor.committeememberNeilson, Andrew P.en_US
dc.contributor.committeememberDean, Dennis R.en_US


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