Biophysical Society Thematic Meeting| Lima 2019

Revisiting the Central Dogma of Molecular Biology at the Single-Molecule Level

Poster Abstracts

23-POS Board 23 EXPLORING THE EFFECTS OF CHIRALITY OF DNA-THREADING INTERCALATORS AT SINGLE MOLECULE LEVEL USING OPTICAL TWEEZERS Adam A Jabak 1 ; Nicholas Bryden 1 ; Fredrik Westerlund 2 ; Per Lincoln 3 ; Micah J McCauley 4 ; Ioulia Rouzina 5 ; Mark C Williams 4 ; Thayaparan Paramanathan 1 ; 1 Bridgewater State University, Department of Physics, Bridgewater, MA, USA 2 Chalmers University of Technology, Department of Biology and Biological Engineering, Gothenburg, Sweden 3 Chalmers University of Technology, Department of Chemistry and Chemical Engineering, Gothenburg, Sweden 4 Northeastern University, Department of Physics, Boston, MA, USA 5 The Ohio State University, Department of Chemistry and Biochemistry, Columbus, OH, USA Using optical tweezers we have been able to study the DNA binding interactions of small molecules and prospective anti-cancer drugs at the single molecule level. A specific type of these small molecules, known as threading intercalators, has a flat planar moiety in between the molecule’s bulky side chains. In order for them to bind with DNA, they have to thread their bulky side chains in between the base pairs. Due to this threading requirement, these molecules tend to have high binding affinities and slow kinetics. We have been investigating the binding properties of the ruthenium-based threading intercalator LL-[µ-bidppz(phen) 4 Ru 2 ] 4+ , or LL-P for short. This complex has the exact chemical components but an opposite chirality to the previously studied DD-P complex. Our data shows that the change in chirality affects the DNA binding kinetics, the association and dissociation rates, to at least a threefold in favor of the left handed LL-P complex. The data also confirms that both the left-handed and the right-handed molecules have a similar binding affinity as a result of their common intercalating moiety. This comparison leads us to a better understanding of how chirality can affect the binding of similar small molecules to DNA. It also will contribute an insight towards improved designs of potential anti-cancer drugs.

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