Date of Award
Master of Science (MS)
Dr. W. David Wilson - Committee Chair
Dr. Kathryn Grant - Committee Member
Dr. Stuart Allison - Committee Member
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.
Hunt, Rebecca Ann, "Determining Topological Effects of Heterocyclic Diamidines with AT Rich DNA: A Study Using Gel Electrophoresis, Mass Spectrometry, and the Polymerase Chain Reaction." Thesis, Georgia State University, 2010.