SEQUENCE-DEPENDENT DISTORTIONS INDUCED IN DNA BY MONOFUNCTIONAL PLATINUM(II) BINDING
SEQUENCE-DEPENDENT DISTORTIONS INDUCED IN DNA BY MONOFUNCTIONAL PLATINUM(II) BINDING
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DOI：
10.1021/bi00164a014
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发表时间：
1992-12-15
期刊：
影响因子：
2.9
通讯作者：
LENG, M
中科院分区：
文献类型：
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作者：
BRABEC, V;REEDIJK, J;LENG, M
研究了氯二乙三胺-铂（II）氯{[Pt(dien)Cl]Cl}单功能加合物对DNA热稳定性和构象的影响。制备了不同长度（9-20个碱基对）和不同中心三核苷酸序列的寡脱氧核糖核苷酸双核苷酸，并对其进行了表征，这些双核苷酸含有位点特异性和独特的N(7)-鸟嘌呤加合物。包括d（AGC）、d（AGT）、d（CGA）、d（TGA）、d（TGC）和d（TGT）序列上的加合物。所有这些单能加合物都降低了双相化合物的熔化温度（T(m)）。这种不稳定效应表现出序列依赖的可变性。对于含有嘧啶-鸟嘌呤-嘧啶中心序列的修饰双链，观察到T(m)的最大降低。不稳定效应随Na+浓度的降低而降低。极谱、圆二色性、菲罗啉-铜和化学探针揭示了在加合物周围的几个碱基对上分布的构象畸变。单功能铂（II）加合物对DNA构象畸变的影响表现出与DNA热稳定性相似的序列依赖性变异性。还研究了顺式二胺单水单氯铂（II）形成的单官能加合物对寡核苷酸双链稳定性的影响。这种损伤降低了DNA的热稳定性，其方式与[Pt(dien)Cl]Cl的加合物相同。
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 (T(m)) of the duplexes. This destabilization effect exhibits a sequence-dependent variability. The highest lowering of T(m) 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.