Does irehdiamine kink DNA?

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Abstract
Equilibrium, relaxation kinetic and transient electric dichroism studies on the complex of the diamino steroid irehdiamine A with DNA [from calf thymus, Microccocus luteus, Escherichia coli, Clostridium perfringens and human placenta]. The results are consistent with a .beta.-kinked structure for the complex at saturation, with a kink in the DNA structure induced by a bound steroid every 2nd base pair. The results that favor this hypothesis include an apparent length decrease of rod-like bacterial DNA molecules when only a small amount of drug is bound, followed by an apparent length increase at saturation. The limiting dichroism amplitude implies a substantial increase in the tilt of the bases relative to the orientation axis; at saturation the base UV transition moments are tilted about 31.degree. from the plane perpendicular to the orientation axis. Because of the polarization of the 260 nm transition moments, the tilt of the bases must be predominantly in the short rather than the long axis of the base pair. The large hyperchroism of the complex is consistent with loss of base stacking, as required by a kinked structure. The kinetic results imply a bimolecular reaction mechanism, with a temperature-dependent association rate constant of roughly 108 M-1 s-1, and a dissociation rate constant of about 5 .times. 103 s-1, nearly independent of temperature. The association activation energy and apparent reaction enthalpy vary from 12-22 kcal mol-1; heat is absorbed on complex formation as expected for loss of base-stacking interactions. An anomalous result of the experiments is the larger apparent length increase (13%) exhibited by 2 eukaryotic DNA, compared to 6% for 3 prokaryotic DNA. Differences were also observed in the kinetic properties of the complexes.