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dc.contributor.authorMetaferia, Belhu B.en_US
dc.date.accessioned2014-03-14T20:14:25Z
dc.date.available2014-03-14T20:14:25Z
dc.date.issued2002-07-18en_US
dc.identifier.otheretd-07282002-181151en_US
dc.identifier.urihttp://hdl.handle.net/10919/28428
dc.description.abstractTaxol™, isolated from the bark of Taxus brevifolia in the late 1960s, and the semisynthetic analog Taxotere™ have proven clinical importance for the treatment of ovarian and breast cancer. Taxol™ exerts its biological effect by binding to polymerized tubulin and stabilizing the resulting microtubules. Studies aimed at understanding the biologically active conformation of taxol and its binding environment on β-tubulin are described. This knowledge is important because it could lead to the design of structurally less complicated drugs with better efficacy and better bioavailability. Moreover, the information can be extended to other natural products that possess microtubule-stabilizing properties similar to Taxol™. In this work, the synthesis of a triply labeled taxol analog is described as well as REDOR studies of this compound complexed to tubulin are in progress. Macrocyclic analogs of taxol have been prepared and their biological activities were evaluated. Chemical modeling of these analogs and their activities agrees with the hypothesis that Taxol™ adopts T-shaped conformation. Difficulties were encountered with the key ring-closing metathesis strategy, suggesting that a more flexible and efficient macrocyclization method will be needed to synthesize additional macrocyclic analogs.en_US
dc.publisherVirginia Techen_US
dc.relation.haspart05-Experimental.PDFen_US
dc.relation.haspart01-cover.PDFen_US
dc.relation.haspart06-Appendix-spectra.PDFen_US
dc.relation.haspart03-Literature.PDFen_US
dc.relation.haspart07-Vita.PDFen_US
dc.relation.haspart04-Projects-Results.PDFen_US
dc.relation.haspart02-Abstract.PDFen_US
dc.rightsI hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Virginia Tech or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.en_US
dc.subjectT-Taxol conformationen_US
dc.subjectTubulinen_US
dc.subjectTaxolen_US
dc.subjectMicrotubulesen_US
dc.subjectMacrocyclic analogsen_US
dc.subjectAnti-cancer agentsen_US
dc.subjectRing-closing olefin metathesisen_US
dc.subjectREDORen_US
dc.subjectROESYen_US
dc.subjectNAMFISen_US
dc.titleSynthesis of Taxol™ Analogs as Conformational Probesen_US
dc.typeDissertationen_US
dc.contributor.departmentChemistryen_US
dc.description.degreePh. D.en_US
thesis.degree.namePh. D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineChemistryen_US
dc.contributor.committeechairKingston, David G. I.en_US
dc.contributor.committeememberTanko, James M.en_US
dc.contributor.committeememberCastagnoli, Neal Jr.en_US
dc.contributor.committeememberCarlier, Paul R.en_US
dc.contributor.committeememberHanson, Brian E.en_US
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-07282002-181151/en_US
dc.date.sdate2002-07-28en_US
dc.date.rdate2003-07-31
dc.date.adate2002-07-31en_US


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