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dc.contributor.authorSalim, Sameren_US
dc.date.accessioned2005-03-01T19:35:50Z
dc.date.available2005-03-01T19:35:50Z
dc.date.issued2004-12-03en_US
dc.identifier.urihttp://hdl.handle.net/1853/4867
dc.description.abstractIt has recently been shown that the binding site of SAHase, an enzyme critical in the replication mechanism of viruses, is quite flexible and exhibits a large difference between the "open" and "closed" conformations, thus presenting an obstacle towards design efforts. As a possible solution to this dilemma, we have strategically designed and synthesized a series of structurally innovative nucleosides possessing a heteroaromatic purine ring split into its two components (for example, an imidazole and pyrimidine ring), thereby conferring additional degrees of conformational freedom and torsional flexibility to the ligand. As a result, these molecular "chameleons" can adapt to the environment of the flexible binding site in order to maximize and complement structural interactions, without losing the integrity of the crucial contacts involved in the enzyme's mechanism of action. The synthesis of several proximal analogues is presented herein.en_US
dc.format.extent1898515 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectFlexible enzymesen_US
dc.subjectFlexible inhibitors
dc.subject.lcshNucleosides Synthesisen_US
dc.title"Molecular Chameleons": Design and Synthesis of a Second Series of Flexible Nucleosidesen_US
dc.typeDissertationen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentChemistry and Biochemistryen_US
dc.description.advisorCommittee Member: David M. Collard; Committee Member: Donald F. Doyle; Committee Member: Harish Radhakrishna; Committee Member: Katherine L. Seley; Committee Member: Suzanne B. Shukeren_US


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