Regulation of orientation and the dynamic behavior of metal complexes bound to DNA

与 DNA 结合的金属配合物的方向和动态行为的调节

• 批准号: 12640564
• 负责人: CHIKIRA Makoto
• 金额: $ 1.79万
• 依托单位: Chuo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12640564/
• 关键词: DNA fiber ESR; DNA cleaving reaction; phenathroline copper(II) complex; phenathroline Pt(II) complex; NMR; oligonucleotide; Ni(III) complex; tripeptide; DNA; フェナントロリン白金(II)錯体; ペプチドNi(III)錯体; 金属錯体; ペプチド銅(II)錯体; ポリアミン銅(II)錯体; デグリコペプロマイシン; Ni(

In order to develop effective reagents that cleave DNA oxidatively or hydrolytically, various metal complexes have been synthesized and the reactivity and the DNA binding structures have been investigated.1. Several copper(II) complexes with 4-dentate phenanthroline derivatives with substituents at 2- and 9-postions were synthesized. Bulky substituents that deformed the planarity of the complex enhanced the oxidative cleavage of DNA and the correlation between the reactivity and the binding structure was discussed.2. In the cleaving reaction with ternary copper(II) complexes with phenanthroline and amino acid, the amino acid depresses the reaction. Further lowering of the reactivity was induced by 2,9-dimethyl substituted phenanthroline. These results suggested that cleaving reaction proceeds with the mono-phenanthroline copper(II) complex.3. Binding structures of the ternary platinum(II) complexes of phenanthroline or dipyridine with lysine bound to oligonucleotide DO1 and DO2 were analyzed by NMR. The phenanthroline derivative intercalates between G2 and C3 of DO1 and G4 and A5 of DO2 from the minor groove while the bipyridine derivative binds to the AT site of DO1 in the minor groove. The binding structures were refined by molecular dynamic calculation.4. ESR signals from unstable Ni(III) complexes of histidine-containing tripeptides could be detected by in-situ oxidation of the Ni(II) complex incorporated in DNA. The super-hyperfine splitting from nitrogenous base suggested a presence of the species coordinated to a guanine N7.

为了开发有效的氧化性或水解性DNA裂解试剂，人们合成了各种金属配合物，并对其反应活性和DNA结合结构进行了研究。合成了4-齿状邻菲咯啉衍生物与铜(II)的2位和9位取代基。研究结果如下：1.大量取代基使络合物的平面性发生变形，促进了DNA的氧化切割，并讨论了反应活性与结合结构的关系。在铜(II)与邻菲咯啉和氨基酸的三元配合物的裂解反应中，氨基酸对反应有抑制作用。2，9-二甲基取代邻菲咯啉使反应活性进一步降低。这些结果表明，裂解反应是以单菲咯啉铜(II)络合物进行的。用核磁共振方法分析了邻菲咯啉或联吡啶与赖氨酸三元铂(II)配合物与寡核苷酸DO1和DO2的结合结构。邻菲咯衍生物从小槽插入DO1的G2和C3之间，DO2的G4和A5之间，而联吡啶衍生物则结合到DO1的AT位上。通过分子动力学计算对其结合结构进行了优化。通过原位氧化DNA中的镍(II)络合物，可以检测到不稳定的组氨酸三肽镍(III)络合物的ESR信号。从含氮碱基的超精细分裂表明该物种的存在与鸟嘌呤N7配位。

项目成果

M. Chikira: "Deglycopeplomycin metal complexes on DNA-fibers : a role of sugar moiety for the stability and the orientation of the complexes"J. Inorg. Biochem.. 86・1. 180-180 (2001)

M. Chikira：“DNA 纤维上的去糖霉素金属复合物：糖部分对复合物稳定性和方向的作用”J. Inorg. 86・1 (2001)。

R.Nagane: "Interaction of Cu(II) complexes of tetrapeptides, Arg-Gly-His-Xaa, with DNA"J. Inorg. Biochem.. 86・1. 352-352 (2001)

R.Nagane：“四肽、Arg-Gly-His-Xaa 的 Cu(II) 复合物与 DNA 的相互作用”J. Inorg. 86・1 (2001)。

M.Chikira: "Deglycopeplomycin metal complexes on DNA-fibers : a role of sugar moiety for the stability and the orientation of the complexes"J. Inorg. Biochem.. 86・1. 180-180 (2001)

M. Chikira：“DNA 纤维上的去糖霉素金属复合物：糖部分对复合物稳定性和方向的作用”J. Inorg. 86・1 (2001)。

R. Nagane: "Interaction of Cu(II) complexes of tetrapeptides, Arg-Gly-His-Xaa, with DNA"J. Inorg. Biochem. 86-1. 352-352 (2001)

R. Nagane：“四肽、Arg-Gly-His-Xaa 的 Cu(II) 复合物与 DNA 的相互作用”J。

R.Nagane: "How Amino Acids Control the Binding of Cu (II) Ions to DNA (III) ; A Novel Interaction of Histidine Complex with DNA"J.Inorg.Biochem.. 78・3. 243-249 (2000)

R.Nagane：“氨基酸如何控制 Cu (II) 离子与 DNA (III) 的结合；组氨酸复合物与 DNA 的新型相互作用”J.Inorg.Biochem.. 78・3 (2000)。