Identification and Isolation of Bioactive Natural Product Compounds Targeting Oxysterol-Binding Proteins

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dc.contributor.advisorBiggs, Robyn A.
dc.contributor.authorForrest, Ines
dc.contributor.committeeMemberDuerfeldt, Adam S.
dc.contributor.committeeMemberGlatzhofer, Daniel T.
dc.date.accessioned2020-06-25T16:47:25Z
dc.date.available2020-06-25T16:47:25Z
dc.date.issued2020-06-08
dc.date.manuscript2020-06
dc.description.abstractOSW-1, a plant-derived cholestane glycoside, has been shown to exhibit broad-spectrum antiviral activity by targeting oxysterol-binding protein (OSBP) and potent antiproliferative activity by targeting OSBP-related protein 4 (ORP4). In order to develop OSW-1 and OSW-1-derived compounds as potential antiviral or anticancer therapeutics, an understanding of OSW-1 structure-activity relationships (SAR) for binding to OSBP and ORP4 must be established. This SAR will allow for the identification of compounds with improved pharmacological properties and the development of selective OSBP- or ORP4-targeting compounds. To date, there are no reported protein structures of OSBP or ORP4, and the published research on OSW-1 only provide partial insight into the compound SAR. The major goal of this research project is to purify and identify OSW-1-related natural product compounds from Ornithogalum saundersiae bulbs. The new OSW-1-related compounds can then be subjected to biological testing, including binding to OSBP and ORP4, anticancer assays, and antiviral assays. Through the development of an efficient analytical method for the purification of natural products from Ornithogalum saundersiae, several OSW-1-related compounds, including newly discovered compounds were purified and structurally characterized. Testing the isolated OSW-1-related compounds for OSBP and ORP4 binding will provide further SAR understanding, and progressively guide the discovery and synthesis of new OSBP and ORP4 specific compounds for pre-clinical drug development as new antiviral and anticancer drugs.en_US
dc.identifier.urihttps://hdl.handle.net/11244/324866
dc.languageen_USen_US
dc.subjectBioactive natural products isolationen_US
dc.subjectOxysterol-binding proteinsen_US
dc.subjectExtractionen_US
dc.subjectAnalytical method developmenten_US
dc.subjectBinding affinityen_US
dc.subjectStructure-activity relationshipen_US
dc.subjectStructural elucidationen_US
dc.subjectChemistry, Biochemistryen_US
dc.subjectOSW-1, OSBP, ORP4en_US
dc.thesis.degreeMaster of Scienceen_US
dc.titleIdentification and Isolation of Bioactive Natural Product Compounds Targeting Oxysterol-Binding Proteinsen_US
ou.groupCollege of Arts and Sciences::Department of Chemistry and Biochemistryen_US
shareok.nativefileaccessrestricteden_US

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