Brabec V, Reedijk J, Leng M
Centre de Biophysique Moléculaire, CNRS, Orléans, France.
Biochemistry. 1992 Dec 15;31(49):12397-402. doi: 10.1021/bi00164a014.
The effects on thermal stability and conformation of DNA produced by the monofunctional adducts of chlorodiethylenetriamineplatinum(II) chloride ([Pt(dien)Cl]Cl) have been investigated. Oligodeoxyribonucleotide duplexes of varying lengths (9-20 base pairs) and of varying central trinucleotide sequences were prepared and characterized that contained site-specific and unique N(7)-guanine adducts. Included are adducts at the sequences of d(AGC), d(AGT), d(CGA), d(TGA), d(TGC), and d(TGT). All these monofunctional adducts decrease the melting temperature (Tm) of the duplexes. This destabilization effect exhibits a sequence-dependent variability. The highest lowering of Tm is observed for the modified duplexes containing the central sequence of pyrimidine-guanine-pyrimidine. The destabilization effect is reduced with decreasing concentrations of Na+. Polarography, circular dichroism, phenanthroline-copper, and chemical probes reveal conformational distortions spreading over several base pairs around the adduct. The effects of monofunctional platinum(II) adducts on conformational distortions in DNA exhibit a sequence-dependent variability similar to those on thermal stability of DNA. The influence of the monofunctional adduct formed by cis-diamminemonoaquamonochloroplatinum(II) on the stability of the oligonucleotide duplex has been also studied. This lesion decreases thermal stability of DNA in the same way as does the adduct of [Pt(dien)Cl]Cl.
已对氯化二乙三胺合铂（II）（[Pt(dien)Cl]Cl）的单功能加合物对DNA热稳定性和构象的影响进行了研究。制备并表征了不同长度（9 - 20个碱基对）和不同中央三核苷酸序列的寡脱氧核糖核苷酸双链体，其包含位点特异性且独特的N(7)-鸟嘌呤加合物。其中包括d(AGC)、d(AGT)、d(CGA)、d(TGA)、d(TGC)和d(TGT)序列处的加合物。所有这些单功能加合物均降低了双链体的解链温度（Tm）。这种去稳定化效应呈现出序列依赖性变化。对于含有嘧啶 - 鸟嘌呤 - 嘧啶中央序列的修饰双链体，观察到Tm的降低最为显著。随着Na⁺浓度降低，去稳定化效应减弱。极谱法、圆二色性、邻菲罗啉 - 铜和化学探针显示，加合物周围几个碱基对范围内存在构象扭曲。单功能铂（II）加合物对DNA构象扭曲的影响呈现出与对DNA热稳定性影响类似的序列依赖性变化。还研究了顺 - 二氨一水一氯铂（II）形成的单功能加合物对寡核苷酸双链体稳定性的影响。这种损伤与[Pt(dien)Cl]Cl的加合物一样，以相同方式降低了DNA的热稳定性。
