Abstract: Meredith Skiba
Mentor: Dr. Burgmayer
In order to stop tumor growth, replication enzymes responsible for the increase in cells can be inhibited. Several transition metal compounds may inhibit these enzymes’ activity through their ability to intercalate and photocleave. Intercalation occurs when a molecule slides in between the base pairs of a DNA molecule distorting DNA’s helical shape. This change in shape prevents the replication enzyme from properly interacting with the DNA and thus prevents cell growth. Similarly, photocleavage of DNA further inhibits DNA replication by breaking and uncoiling DNA after UV light exposure. The mechanism by which photocleavage occurs is unclear. However, it is believed that reactive oxygen species may play a role.
In the Burgmayer lab, a family of ruthenium (II) tris-chelate compounds are synthesized and evaluated for their ability to distort DNA through intercalation and photocleavage. These ruthenium compounds possess large planar ligands, which tend to strongly intercalate into DNA. Intercalation is evaluated through viscometry studies. The photocleavage ability of the intercalating ruthenium compounds is examined through gel electrophoresis.
Further viscometry studies will be carried out to evaluate the ability of these ruthenium compounds to intercalate using an Ostwald Viscometer. Additional photocleavage studies will be performed to compare the photocleaving ability of the ruthenium compounds to each other, as well as the optimal ruthenium concentrations for DNA photocleavage of each individual ruthenium compound. Studies will also be carried out to investigating the impact of other metals on the photocleaving ability of the various ruthenium compounds.