The spermine-bisaryl conjugate as a potent inducer of B- to Z-DNA transition

DNA containing alternating purine and pyrimidine repeats has the potential to adopt the Z-DNA structure, one of the well-studied structures besides A- and B-DNA. Despite a number of molecular models that have been proposed to explain the mechanism for B→Z transition, there is continued discussion on the mechanism and physiological role of this transition. In this study, we have found that the bis(2-naphthyl)-maleimide-spermine conjugate (3c) exhibits a remarkable ability to cause the B→Z transition of d(CGCGCG)₂ at low salt concentrations. Using isothermal titration calorimetry (ITC) we show that the B→Z transition induced by 3c is both enthalpically and entropically favorable. The ligand might effect the dehydration of B-DNA, which leads to the B→Z transition. Interestingly, an intermediate CD between the B and Z forms was observed in the pH-dependent transition in the presence of the ligand. The unique structure and characteristics of the ligand designed in this investigation will be useful for the study of Z-DNA. From B to Z: The bis(2-naphthyl)maleimide-spermine conjugate shown in the figure exhibits a remarkable ability to cause the B→Z transition of d(CGCGCG)₂ at low salt concentrations. A stable intermediate between the B and Z forms was observed in the presence of the ligand at about pH 8.