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 (3 c) 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 3 c 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.