Date of Award


Degree Type

Closed Thesis

Degree Name

Master of Science (MS)



First Advisor

Dr. W. David Wilson - Committee Chair

Second Advisor

Dr. Kathryn Grant - Committee Member

Third Advisor

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.