Genomic DNA is organized around the double-stranded of B-form DNA, which is both durable and flexible enough to store and pass on genetic information. Once freed from the associations of an extended complimentary sequence, single stranded DNA and RNA can adopt a vast array of stable secondary structure motifs, such as stem-loop, pseudo-knots, and tetra-loops, ideal for its involvement in biological settings other than as a store of genetic information. Originally, alkylating agents were used as "mustard gas" and related chemical weapons in World War I. Alkylating agents, in general, can react with one or two different 7-N-guanine residues and could potentially result in the cross-linkage of DNA strands, preventing uncoiling of the DNA double helix leading to cell death. More recent evidence show that guanine-rich nucleic acids can fold into distinctive four-stranded conformers found in telomeric DNA repeats (i.e. TTAGGG), also known as G-quadruplexes (G4), as well as in sequences in the promoter and other regulatory regions of genes, especially those involved in cellular proliferation. Small molecules that induce the formation of, and selectively bind to, G4 structures are of interest for development as potential anticancer therapeutics. Novel 10-oxoanthracene and substituted anthracenyl isoxazole esters (AIEs) were synthesized and characterized based on NMR studies. To date, quarfloxin is the only G-quadruplex ligand from the large number developed to progress to clinical evaluation. The synthesis, structural characterization, and biological studies will be presented.
| Identifer | oai:union.ndltd.org:MONTANA/oai:etd.lib.umt.edu:etd-06242013-134023 |
| Date | 28 June 2013 |
| Creators | Duncan, Nathan S |
| Contributors | Nicholas R Natale, Howard Beall, Michael Braden, Orion Berryman |
| Publisher | The University of Montana |
| Source Sets | University of Montana Missoula |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.umt.edu/theses/available/etd-06242013-134023/ |
| Rights | unrestricted, I 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 University of Montana 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. |
Page generated in 0.0408 seconds