Studies of natural products that reveal novel strategies for efficient modification of DNA

MOspace/Manakin Repository

Breadcrumbs Navigation

Studies of natural products that reveal novel strategies for efficient modification of DNA

Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/4452

[-] show simple item record

dc.contributor.advisor Gates, Kent S. (Kent Stephen), 1962- en
dc.contributor.author Szekely, Joseph, 1973- en_US
dc.date.accessioned 2010-01-12T17:07:37Z
dc.date.available 2010-01-12T17:07:37Z
dc.date.issued 2006 en_US
dc.date.submitted 2006 Spring en
dc.identifier.other SzekelyKJ-051606-D5140 en_US
dc.identifier.uri http://hdl.handle.net/10355/4452
dc.description The 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. en_US
dc.description Title from title screen of research.pdf file (viewed on April 24, 2009) en_US
dc.description Vita. en_US
dc.description Includes bibliographical references. en_US
dc.description Thesis (Ph.D.) University of Missouri-Columbia 2006. en_US
dc.description Dissertations, Academic -- University of Missouri--Columbia -- Chemistry. en_US
dc.description.abstract DNA 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. en_US
dc.language.iso en_US en_US
dc.publisher University of Missouri--Columbia en_US
dc.relation.ispartof 2006 Freely available dissertations (MU) en_US
dc.subject Leinamycin. en_US
dc.subject Leinamycin en_US
dc.subject.lcsh DNA damage en_US
dc.subject.lcsh Chemical reactions en_US
dc.subject.lcsh Natural products en_US
dc.title Studies of natural products that reveal novel strategies for efficient modification of DNA en_US
dc.type Thesis en_US
thesis.degree.discipline Chemistry en_US
thesis.degree.grantor University of Missouri--Columbia en_US
thesis.degree.name Ph.D. en_US
thesis.degree.level Doctoral en_US
dc.identifier.merlin .b67058565 en_US
dc.identifier.oclc 319169212 en_US
dc.relation.ispartofcommunity University of Missouri-Columbia. Graduate School. Theses and Dissertations. Dissertations. 2006 Dissertations


This item appears in the following Collection(s)

[-] show simple item record