On the subtle competition between groove binding and intercalation of small drugs with deoxyribonucleic acid (DNA): The case of chloroquine

We performed single molecule force spectroscopy assays to elucidate the competition between the two binding modes (intercalation and groove binding) that occur between the drug chloroquine (CLQ) and DNA in HEPES-based buffers. Force–extension curves were obtained under different drug concentrations and buffer compositions, allowing the determination of the changes on the mechanical parameters of these complexes and the physical chemistry of the interactions. The presence of HEPES in the buffer, when combined with NaCl, can modulate the interaction. The conclusions allowed us to advance in the understanding of the role of the driving forces in the balance between distinct binding modes.