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dc.contributor.advisorGates, Kent S. (Kent Stephen), 1962-eng
dc.contributor.authorSzekely, Joseph, 1973-eng
dc.date.issued2006eng
dc.date.submitted2006 Springeng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionTitle from title screen of research.pdf file (viewed on April 24, 2009)eng
dc.descriptionVita.eng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionThesis (Ph.D.) University of Missouri-Columbia 2006.eng
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- Chemistry.eng
dc.description.abstractDNA is the central molecule in cells. The correct function of cells depends on the structure of DNA. DNA damaging natural products often show cytotoxic or mutagenic properties, which many times land them medicinal value as antibacterial or anticancer therapeutics. Efficient DNA modifications by these agents usually endow them with outstanding biological efficiency. In the present dissertation, we investigated novel DNA damaging natural products with novel DNA modification strategies. We showed that weak noncovalent binding of the natural product leinamycin to DNA accelerates its DNA-alkylation reaction (Chapter 1). We demonstrated that leinamycin intercalates DNA with an unprecedented DNA-intercalating functional group. Likewise, we uncovered novel molecular recognition features of the natural product azinomycin using similar tools (Chapter 4). We characterized novel, reversible chemical reactions of leinamycin (Chapter 3). Amongst these were reversible DNA-alkylation and reversible adduct formation with biologically relevant nucleophiles. We showed that thiols and chloride ion can add to the leinamycin episulfonium ion reveribly to protect it from unproductive hydrolysis and to help its transport to DNA. We synthesized Precursors.eng
dc.identifier.merlin.b67058565eng
dc.identifier.oclc319169212eng
dc.identifier.otherSzekelyKJ-051606-D5140eng
dc.identifier.urihttp://hdl.handle.net/10355/4452eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.subjectLeinamycin.eng
dc.subjectLeinamycineng
dc.subject.lcshDNA damageeng
dc.subject.lcshChemical reactionseng
dc.subject.lcshNatural productseng
dc.titleStudies of natural products that reveal novel strategies for efficient modification of DNAeng
dc.typeThesiseng
thesis.degree.disciplineChemistry (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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