Interaction of DNA with tilorone derivatives: viscometric investigations

Abstract

Interaction of DNA with tilorone and six of its derivatives was studied in solution. This was done by viscosity measurements on both low and high molecular weight calf thymus DNA, in order to interpret the experimental results in terms of changes of DNA contour length (intercalation) and of persistence length (stiffening and bending). Qualitative and semiquantitative analysis delivered the following results: The carbonyl derivatives of tilorone bind more strongly to DNA than tilorone itself. The ligands with their two positively charged terminal groups favour DNA-DNA association. All carbonyl derivatives studied intercalate completely whereas the compound with quaternary nitrogens does not. No significant DNA stiffening effects were observed (contrary to the interaction of DNA with anthracycline derivatives) indicating the absence of a strong multipoint clamping between ligand and helix in relatively great distance. Different ligands induce different helix bending effects. The magnitude of the helix bending angle probably depends on the DNA base sequence. For some derivatives this angle is different at low and high ratio vt of added ligand molecules per DNA phosphate. This novel observation suggests the existence of heterogeneous, i.e. specific, binding as also found for tilorone by other authors on the basis of spectroscopic measurements using synthetic polynucleotides.