BI-3802 is a relatively new anticancer drug known to bind to the transcription repressor BCL6 which can lead to the regression of the most common form of cancer in the lymphatic system, B-cell lymphoma. Based on the structure of BI-3802 we believe this small molecule drug can bind to DNA through intercalation. Intercalators are a special type of molecule which have a flat planar section that can stack between DNA base pairs. In this study, we use Optical tweezers to trap a single DNA molecule in order to explore the binding of BI-3802 with DNA. Once we trap a single DNA molecule, we stretch the DNA and measure the tension in the DNA as a function of extension. During this process, at a certain force, the DNA undergoes aphase transition from double stranded DNA (dsDNA) to single stranded DNA (ssDNA). DNA stretching is repeated in the presence of various concentrations of BI-3802 in order to study the interaction between the drug and DNA at the molecular level. Our results suggest that the force where the phase transition from dsDNA to ssDNA occurs is decreased as the concentration of BI-3802 is increased, indicating this drug destabilizes the naturally occurring double stranded structure of DNA at micromolar concentrations. To our knowledge this is the first study that explores the interactions of BI-3802 with DNA at the single molecule level. The outcome of these experiments may help us better understand drug interactions at the molecular level and help develop new therapeutics.
Physics, Photonics and Optical Engineering
Dr. Thayaparan Paramanathan, Thesis Advisor
Dr. Edward Deveney, Committee Member
Dr. Elif Demirbas, Committee Member
McAuliffe, Jared. (2022). Exploring the Binding of Anticancer Drug BI-3802 with DNA Using Optical Tweezers. In BSU Honors Program Theses and Projects. Item 582. Available at: https://vc.bridgew.edu/honors_proj/582
Copyright © 2022 Jared McAuliffe