Wu P K, Kharatishvili M, Qu Y, Farrell N
College of Medicine, University of Vermont, Burlington, USA.
J Inorg Biochem. 1996 Jul;63(1):9-18. doi: 10.1016/0162-0134(95)00163-8.
Dinuclear bis(platinum) complexes have been shown previously to induce the B-->Z transition in synthetic DNAs (Nucleic Acids Res. 7, 1697-1703, J. Inorganic Biochem. 54, 207-220). In this paper, the reversibility of the Z conformation back to the B form was assessed by treatment of the induced Z form in poly(dG-dC).poly(dG-dC) with ethidium bromide (Etd). Z-DNA induced by the tetra-amine cations [{Pt(NH3)3}2(H2N(CH2)nNH2)]4+, which are capable of only electrostatic interactions with the polynucleotide, was readily reversible. The spectroscopic data mirrored that of ethidium bromide/poly(dG-dC).poly(dG-dC) in the presence of 4.4 M NaCl. In contrast, Z-DNA induced by the bifunctional complexes [{trans-PtCl(NH3)2}2(H2N(CH2)nNH2)]2+ did not produce spectra typical of Etd intercalation and reversal to B-form DNA. The original Z-form CD spectra of DNA treated with the bifunctional complexes could be reobtained following removal of Etd by extensive dialysis. The bifunctional complexes are very effective interstrand cross-linking agents. The data suggest that interstrand cross-linking by dinuclear complexes can stabilize or "lock" the Z-conformation prohibiting its reversal to the B-form. The implications for the biological activity of the dinuclear complexes are briefly discussed.
双核双（铂）配合物此前已被证明能在合成DNA中诱导B→Z转变（《核酸研究》7，1697 - 1703；《无机生物化学杂志》54，207 - 220）。在本文中，通过用溴化乙锭（Etd）处理聚（dG - dC）·聚（dG - dC）中诱导产生的Z型构象，评估了Z构象向B型构象逆转的可逆性。由仅能与多核苷酸发生静电相互作用的四胺阳离子[{Pt(NH3)3}2(H2N(CH2)nNH2)]4 +诱导产生的Z - DNA很容易逆转。光谱数据反映了在4.4 M NaCl存在下溴化乙锭/聚（dG - dC）·聚（dG - dC）的光谱数据。相比之下，由双功能配合物[{trans - PtCl(NH3)2}2(H2N(CH2)nNH2)]2 +诱导产生的Z - DNA并未产生典型的Etd嵌入光谱，也未逆转回B型DNA。在用双功能配合物处理的DNA的原始Z型圆二色光谱在通过广泛透析去除Etd后可以重新获得。双功能配合物是非常有效的链间交联剂。数据表明，双核配合物的链间交联可以稳定或“锁定”Z构象，阻止其逆转回B型构象。本文简要讨论了双核配合物的生物活性意义。
