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.
Doi
Issei
I
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan.
Tsuji
Genichiro
G
Kawakami
Kyoko
K
Nakagawa
Osamu
O
Taniguchi
Yosuke
Y
Sasaki
Shigeki
S
D001483:Base Sequence; D002151:Calorimetry / Q000379:methods; D002942:Circular Dichroism; D043542:DNA, Z-Form / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D013096:Spermine / Q000737:chemistry*; D013816:Thermodynamics
D043542:DNA, Z-Form; D013096:Spermine