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Threading intercalators are small molecules that bind to DNA by threading their side chains through the DNA bases to intercalate their middle planar section between the DNA base pairs. The high binding affinity and slow dissociation rates of threading intercalators have put them in the class of prospective anti-cancer drugs. In this study we explore the binding of a specific threading intercalator, a binuclear ruthenium complex ΛΛ-P (ΛΛ-[μ-bidppz(phen)4Ru2]4+) using optical tweezers. A single DNA molecule is held at a constant force and the small molecules are introduced to the system in various concentrations until equilibrium is achieved. Measurements of DNA extension at various concentrations of ΛΛ-P as a function of time can be used to estimate the DNA equilibrium binding affinity and binding kinetics for this molecule. Data analysis has revealed that ΛΛ-P possess slightly lower binding affinity than the previously studied binuclear ruthenium complex ΔΔ-P, which is a similar molecule varying only in the handedness of the side chains. The binding kinetics suggests relatively faster and force independent off rates in contrast to previously studied ΔΔ-P, which directly correlated to the locking mechanism of ΔΔ-P. These findings suggest that the change in side chain chirality may have a significant effect on the binding mechanism of small molecules to DNA.



Thesis Comittee

Thayaparan Paramanathan (Thesis Mentor)

Edward Deveney

Steven Haefner

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Original document was submitted as an Honors Program requirement. Copyright is held by the author.

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