Using optical tweezers, we have been able to study the interactions of small molecules and prospective cancer drugs with DNA. One type of these molecules, known as threading intercalators, has a flat planar intercalating moiety in between the molecule’s bulky ancillary supporting ligands. In order to bind with DNA, they have to thread their bulky ancillary ligands in between the DNA base pairs. Due to this requirement for binding, these molecules tend to have high binding affinities and slow kinetics. In this thesis, we explore the binding properties of a ruthenium-based threading intercalator -[μ-bidppz(phen)4Ru2]4+, or -P for short. The goal being to compare the binding properties of this complex with the previously studied -P complex, which has the exact chemical components but an opposite chirality (handedness). Our data suggests that left-handed molecules (-P) bind less favorably to DNA with slower binding kinetics and lower binding affinity than the right-handed molecules (-P). These differences are explained by the nano-scale structural changes that occur at the molecular level during the threading intercalation process. This comparison provides us a better understanding of how chirality affects the binding to DNA and will contribute towards improved designs of potential cancer treatment drugs.
Dr. Thayaparan Paramanathan, Thesis Advisor
Dr. Edward F. Deveney, Committee Member
Dr. Steven C. Haefner, Committee Member
Copyright and Permissions
Original document was submitted as an Honors Program requirement. Copyright is held by the author.
Jabak, Adam A.. (2020). The Effect of Chirality on DNA Threading: Exploring Binuclear Ruthenium lntercalators Using Optical Tweezers. In BSU Honors Program Theses and Projects. Item 333. Available at: https://vc.bridgew.edu/honors_proj/333
Copyright © 2020 Adam A. Jabak