Ushay H M, Santella R M, Caradonna J P, Grunberger D, Lippard S J
Nucleic Acids Res. 1982 Jun 11;10(11):3573-88. doi: 10.1093/nar/10.11.3573.
Chlorodiethylenetriamineplatinum(II) chloride, [(dien)PtCl]Cl, bound to less than or equal to 10% of the nucleotide bases of poly(dG-dC) . poly(dG-dC) reduces the amount of ethanol necessary to bring about the B goes to Z conformational transition in proportion to the amount of platinum complex bound as monitored by CD spectroscopy. The transition may be effected by 25% ethanol with 9.3% of the bases modified polymer an ethanol with 5.4% of the bases modified. With an unmodified polymer an ethanol concentration of 55-60% is necessary to bring about the transition. The assignment of the Z conformation was supported by 31P NMR spectroscopy. This covalent modification of the DNA is reversed by treatment with cyanide ion after which the normal amount of ethanol is necessary to achieve the transition. The platinum complex shows no enhanced binding to DNA in the Z versus the B conformation. Between 20 and 33% (saturation binding) modification, [(dien)PtCl]Cl binds cooperatively to the heterocopolymer as judged by CD spectroscopy. At this high level of modification it is no longer possible to induce the Z DNA structure with ethanol. When [(dien)PtCl]Cl is bound to preformed (with ethanol) Z DNA at saturating levels the CD spectrum is altered but reverts to the spectrum of highly modified DNA upon removal of ethanol. The antitumor drug cis-diaminedichloroplatinum(II), cis-DDP, binds to poly(dG-dC) . poly(dG-dC) and alters the CD spectrum. It does not facilitate the B goes to Z conformational change, however, and actually prevents it from happening even at very high ethanol concentrations.
二氯二乙三胺铂(II)氯化物,即[(dien)PtCl]Cl,与聚(dG-dC)·聚(dG-dC)中小于或等于10%的核苷酸碱基结合。如通过圆二色光谱监测,[(dien)PtCl]Cl与聚(dG-dC)·聚(dG-dC)结合会按结合的铂配合物的量成比例地减少引发B型向Z型构象转变所需的乙醇量。对于9.3%碱基被修饰的聚合物,25%的乙醇即可引发转变;而对于5.4%碱基被修饰的聚合物,5.4%的乙醇就能引发转变。对于未修饰的聚合物,则需要55 - 60%的乙醇浓度才能引发转变。31P核磁共振光谱支持了Z型构象的归属。用氰离子处理后,DNA的这种共价修饰会被逆转,之后实现转变就需要正常量的乙醇。铂配合物在Z型构象与B型构象中对DNA的结合并无增强。通过圆二色光谱判断,在20%至33%(饱和结合)修饰之间,[(dien)PtCl]Cl与该杂聚物协同结合。在这种高修饰水平下,不再能用乙醇诱导出Z-DNA结构。当[(dien)PtCl]Cl以饱和水平与预先形成的(用乙醇)Z-DNA结合时,圆二色光谱会改变,但去除乙醇后会恢复为高度修饰DNA的光谱。抗肿瘤药物顺二氯二氨铂(II),即顺铂,与聚(dG-dC)·聚(dG-dC)结合并改变圆二色光谱。然而,它并不促进B型向Z型的构象变化,实际上即使在非常高的乙醇浓度下也会阻止这种变化发生。