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dc.contributor.authorDennison, Kelly Joyen_US
dc.date.accessioned2006-01-18T22:26:00Z
dc.date.available2006-01-18T22:26:00Z
dc.date.issued2005-11-28en_US
dc.identifier.urihttp://hdl.handle.net/1853/7582
dc.description.abstractThe primary goals of our research are to understand the virology and enzymology of human T-cell leukemia virus type I (HTLV-I) that will lead to the development of treatments for patients infected with HTLV-I. HTLV-I is an oncogenic virus of the Retroviridae family and is the causative agent of adult T-cell leukemia/lymphoma (ATL), tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). HTLV-I has been classified as a dangerous emerging pathogen by the Centers for Disease Control and Prevention with at least 20 million people infected with the virus. This is a significant problem because there are currently no effective treatments to control HTLV-I infection and prevent or treat HTLV-I induced ATL and TSP/HAM. The protease is necessary for retroviral maturation and replication and is, therefore, an attractive target for inhibitor design. Investigation of peptide mimetic compounds incorporating the tetrahedral intermediate of aspartyl protease catalyzed cleavage are crucial for the development of lead inhibitors. Compounds containing statine, 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), or hydroxyethylamine (HEA) are presented in this work. The best compound was a statine-based inhibitor, which had a Ki = 29 +/- 4 nM and 88% inhibition against an HTLV-I protease native substrate in a FRET assay.en_US
dc.format.extent6193249 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectEnzymologyen_US
dc.subjectFluorescence quenching
dc.subjectHTLV-I (Virus)
dc.subjectKinetics
dc.subjectMutation (Biology)
dc.subjectProtease inhibitors
dc.titleUnderstanding HTLV-I Enzymology and Preparation and Characterization of Lead Inhibitors for the Treatment of HTLV-I Infectionen_US
dc.typeDissertationen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentChemistry and Biochemistryen_US
dc.description.advisorCommittee Chair: Dr. Suzanne B. Shuker; Committee Co-Chair: Dr. Thomas M. Orlando; Committee Member: Dr. Andreas S. Bommarius; Committee Member: Dr. C. David Sherrill; Committee Member: Dr. Donald F. Doyle; Committee Member: Dr. S. Michele Owen; Committee Member: Dr. Vicky L. H. Bevilacquaen_US


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