Diamidines are compounds with antiparasitic properties that target the minor groove of DNA. The mechanism of action of these compounds is unknown, but topological changes to DNA structure are a possibility. In this study, we have developed a polyacrylamide gel based screening method to determine topological effects of diamidines on four target sequences: AAAAA, TTTAA, AAATT, and ATATA. The changes caused are sequence dependent, but generally the effect on AAAAA and AAATT is the same while the effect on TTTAA and ATATA is the same. A few compounds show interesting sequence dependent topological effects in the polyacrylamide screening method that could be caused by the compound forming a dimer. Mass spectrometry is used to determine the stoichiometry of DNA-compound complexes. Once compounds show topological effects in the screening method, a bent fragment of kinetoplast DNA is isolated to determine if the same effects occur with DNA from a parasite.
| Identifer | oai:union.ndltd.org:GEORGIA/oai:digitalarchive.gsu.edu:chemistry_theses-1030 |
| Date | 01 April 2010 |
| Creators | Hunt, Rebecca Ann |
| Publisher | Digital Archive @ GSU |
| Source Sets | Georgia State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Chemistry Theses |
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