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dc.contributor.authorChong, Youhoon
dc.date.accessioned2014-03-03T20:28:59Z
dc.date.available2014-03-03T20:28:59Z
dc.date.issued2003-08
dc.identifier.otherchong_youhoon_200308_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/chong_youhoon_200308_phd
dc.identifier.urihttp://hdl.handle.net/10724/21006
dc.description.abstractNucleoside analogues continue to be important drug regimens as part of antiviral therapy. However, because of drug toxicity, and the lack of a durable response due to resistance, there is clearly a need for new compounds to cope with these drawbacks. For this purpose, we developed novel nucleoside analogues and several protocols for molecular modeling studies which can provide a plausible mechanism of antiviral drug resistance conferred by mutation in HIV-1 reverse transcriptase (RT) as well as HBV polymerase. Thus, our recent efforts in the area of molecular modeling studies of HIV-1 RT and drug resistance by mutant RT were reviewed in Chapter 1. In Chapter 2, a divergent synthesis of D- and L- carbocyclic 4’-fluoro-2’,3’-dideoxynucleosides is described. Development of an efficient process for preparing a synthetically useful intermediate, L-2-deoxy ribose is described in Chapter 3, followed by a discussion of the enantiomeric synthesis of D-2’- fluoro-4’-thio-2’,3’-unsaturated nucleosides and their potent antiviral activities in Chapter 4. Chapter 5 deals with a structure-activity relationship study of L-3’-fluoro-2’, 3’-unsaturated nucleosides, and another structure-activity relationship study of D-3’- fluoro-4’-thio-2’,3’-unsaturated nucleosides is described in Chapter 6. Several molecular modeling studies of HIV-1 RT and HBV polymerase complexed with various nucleoside analogues are discussed in the next five chapters: AZT, 3TC and D-dioxolane guanine (DXG) against AZT/3TC resistant RT (Chapter 7), L-FMAU against HBV polymerase (Chapter 8), dioxolane nucleosides against 3TC-resistant RT (Chapter 9), 3’-substituted L-nucleosides against 3TC-resistant HBV polymerase (Chapter 10) and fluorinated cytidine analogues against HIV-1 RT (Chapter 11). Finally, various attempts for the synthesis of hereto unknown 1’-fluororibonucleoside are detailed in Chapter 12.
dc.languageeng
dc.publisheruga
dc.rightspublic
dc.subjectCarbocyclic nucleosides
dc.subject2-deoxy ribose
dc.subject4? -thionucleosides
dc.subject3? -fluoro-2? ,3? -unsaturated nucleosides
dc.subject3? -fluoro-4? -thionucleosides
dc.subjectmolecular modeling
dc.subjecthuman immunodeficiency virus (HIV)
dc.subjectdrug resistance
dc.subjecthepatitis B virus (HBV)
dc.subjectL-FMAU and homolog
dc.titleTowards the discovery of antiviral nucleosides
dc.title.alternativesynthesis, antiviral activity and molecular mechanism of drug resistance
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentPharmacy (Medicinial Chemistry)
dc.description.majorPharmacy (Medicinial Chemistry)
dc.description.advisorChung K. Chu
dc.description.committeeChung K. Chu
dc.description.committeeJ. Warren Beach
dc.description.committeeAnthony C. Capomacchia
dc.description.committeeLarry B. Hendry
dc.description.committeeVasu Nair


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