Targeting G-Quadruplex DNA using Groove Binding Compounds as an Anticancer Study

Authors: AnaSophia Lee, Ruel McKnight, Gadeer Al-Abdely

SUNY Campus: SUNY Geneseo

Presentation Type: Poster

Location: UU 111

Presentation #: 64

Timeslot: Session A 9:00-10:00 AM

Abstract: This research project investigates the effectiveness of groove binding compounds in binding to G-quadruplex DNA. Previous work by researchers within the field have shown that G-quadruplex (G4) DNA is a viable anticancer therapeutic target. Compounds that stabilize G4 have shown promising antitumor effects in preclinical cancer models. This project seeks to study drug-G4 interactions using fluorescence displacement assays and circular dichroism (CD) spectroscopy. Thioflavin-T (ThT) fluorescence displacement data have shown significant displacement of ThT bound to G4 DNA with certain groove binders, indicating G4 binding and stabilization. Circular dichroism spectroscopy displays the differential absorption of circular polarized light in the presence of chiral carbons such as those that exist in a sample of DNA. Each molecule will have a unique spectra, so when a drug is incrementally added to it, each sample generates a new spectra. We have observed noticeable shifts in the CD spectra when the groove binders of this study were added to G4 DNA. This indicates a change in structure and potential stability of the G4 DNA. Our research lab is currently interested in the drugs/groove binders: DAPI, Hoescht33258, distamycin, and berenil. Upon comparison of the results of CD spectroscopy and fluorescence displacement between telomeric and c-MYC G4 DNA, we have seen a difference in binding affinity and structural change that will be studied further. We plan to add other groove binders (e.g., netropsin) to our toolbox for future comparisons and evaluations.