Investigations into the interactions between DNA and conformationally constrained pyridylamineplatinum(II) analogues of AMD473.
Investigations into the interactions between DNA and conformationally constrained pyridylamineplatinum(II) analogues of AMD473.
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研究 DNA 与 AMD473 构象受限的吡啶胺铂 (II) 类似物之间的相互作用。
DOI：
10.1021/ic0340231
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发表时间：
2003
影响因子：
4.6
通讯作者：
T. Hambley
中科院分区：
文献类型：
--
作者：
Vivienne P. Munk;C. Diakos;L. T. Ellis;R. Fenton;B. Messerle;T. Hambley
报道了对映体纯的[PtCl2(AMP)](AMP=2-吡啶甲胺)[PtCl2(R-PEA)]和[PtCl2(S-PEA)](PEA=1-(2-吡啶)乙胺)的合成和晶体结构。研究了[PtCL(2)(AMP)]及其对映体与d(GPG)和52碱基对的寡核苷酸的反应。每一次与d(GPG)的反应都产生了三个铂双官能团d(GPG)物种，比例为1：2：1。这些物种是一对异构体，其中一个异构体以一对缓慢相互转化的旋转异构体形式存在，可以用高效液相色谱分离，但在37℃下5天后重新平衡。吡啶烷基胺配体的吡啶基团被限制在配位平面上，因此，相邻鸟嘌呤的铂-N7键的旋转受到高度限制。对[Ptd(GPG)(AMP)]的异构体进行了2D核磁共振研究，确定其为d(GPG)的5‘-鸟氨酸附近含有吡啶的异构体。三个[PtCL(2)(py-R)]配合物(Py-R=AMP或PEA)分别与一个52碱基对的寡核苷酸反应生成三个相同的双功能d(GPG)加合物，其比例与与d(GPG)的反应比例大致相同，表明立体选择性可忽略不计的是配合物与双链DNA之间的相互作用。
The syntheses of [PtCl(2)(amp)] (amp = 2-pyridylmethylamine) and enantiomerically pure [PtCl(2)(R-pea)] and [PtCl(2)(S-pea)] (pea = 1-(2-pyridyl)ethylamine) and the crystal structure of [PtCl(2)(R-pea)] are reported. The reactions of [PtCl(2)(amp)] and of the enantiomers of [PtCl(2)(pea)] with d(GpG) and with a 52-base-pair oligonucleotide were investigated. Each of the reactions with d(GpG) resulted in the formation of three platinated bifunctional d(GpG) species in a ratio of 1:2:1. These species were shown to be a pair of isomers, one of which exists as a pair of slowly interconverting rotamers that can be separated by HPLC but reequilibrate after 5 days at 37 degrees C. The pyridyl moieties of the pyridylalkylamine ligands are constrained to lie in the coordination plane, and as a consequence, the rotation about the Pt-N7 bond of the adjacent guanine is highly restricted. 2D NMR investigations were carried out on the isomer of [Ptd(GpG)(amp)] that did not form separable rotamers and identified it as the isomer having the pyridine adjacent to the 5'-guanine of the d(GpG). The reaction of each of the three [PtCl(2)(py-R)] complexes (py-R = amp or pea) with a 52-base-pair oligonucleotide resulted in the formation of the same three bifunctional d(GpG) adducts in approximately the same ratios as the reactions with d(GpG), indicating that negligible stereoselectivity results from interactions between the complexes and duplex DNA.