• Small Molecule Drug Interactions with DNA

Many small molecules (such as drugs, ligands, etc.) are able to recognize and bind to single-or double-stranded nucleic acids, often inducing structural alterations. The unique double helix structures of DNA allows for binding through various modes including covalent binding (DNA-adducts), major or minor groove binding, and intercalation. Currently, little is known about small molecule drug interactions with highly packaged DNA that is typically found within cells. The reactivity of drugs and mutagens toward packaged DNA is presumably quite different from dilute DNA, and dependent on both accessibility and changes in DNA-DNA interaction energies. We are working on measuring directly the forces induced by these DNA drug interactions on DNA molecules in various states of condensation and correlating these forces to DNA packaging, DNA damage and disease.