Alternative DNA structures play critical roles in fundamental biological processes linked to human diseases. Thus, targeting and stabilizing these structures by specific ligands could affect the progression of cancer and other diseases. Here, we describe, using methods of molecular biophysics, the interactions of two oxidatively locked [Co2L3]6+ cylinders, rac-2 and meso-1, with diverse alternative DNA structures, such as junctions, G quadruplexes, and bulges. This study was motivated by earlier results demonstrating that both Co(III) cylinders exhibit potent and selective activity against cancer cells, accumulate in the nucleus of cancer cells, and prove to be efficient DNA binders. The results show that the bigger cylinder rac-2 stabilizes all DNA structures, while the smaller cylinder meso-1 stabilizes just the Y-shaped three-way junctions. Collectively, the results of this study suggest that the stabilization of alternative DNA structures by Co(III) cylinders investigated in this work might contribute to the mechanism of their biological activity.

Czech Academy of Sciences Institute of Biophysics CZ 61200 Brno Czech Republic

Czech Academy of Sciences Institute of Biophysics CZ 61200 Brno Czech Republic; Department of Biophysics Faculty of Science Palacky University CZ 78371 Olomouc Czech Republic

Department of Chemistry University of Otago Dunedin 9016 Otago New Zealand

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Ni(II) Cylinders Damage DNA in Cancer Cells and Preferentially Bind Y-Shaped DNA Three-Way Junctions Blocking DNA Synthesis