Development of functional molecules capable of recognizing and cleaving the bulge structure in DNA by using an optical active dinuclear iron complex

利用光学活性双核铁络合物开发能够识别和切割 DNA 凸起结构的功能分子

• 批准号: 16590031
• 负责人: KUROSAKI Hiromasa
• 金额: $ 2.37万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590031/
• 关键词: optical active; DNA; iron complex; restriction enzyme; 錯体; 電子スペクトル

DNA cleaving reagent is an essentical tool for the treatment of cancers and hereditary diseases. It is expected that the reagents that can cleavage specific sequence and specific structure of DNA selectively can be applied to the antitumor drugs and the artificial restriction enzymes.In my approach to develope novel optical active dinuclear iron complexes that are capable of cleaving double-strand DNA simultaneously and sequence-selectively, I prepared six dinuclear ligands, (1,8-(N-anthranylmethyl)-bis(N',N'-dipyridylmethyl-(R,R) or (S,S)-cyclohexane-1,2-diamine (R or S-ABDC), 1,3-(N-xylylmethyl)-bis(N',N'-dpyridylmethyl-(R,R) or (S,S)-cyclohexane-1,2-diamine (m-R-BDC or m-S-BDC), and 1,4-(N-xylylmethyl)-bis(N',N'-dpyridylmethyl-(R,R) or (S,S)-cyclohexane-1,2-diamine (p-R-DBC or p-S-BDC).Moreover, I investigated plasmid pUC 19 DNA cleaving activity by iron complexes, which are prepared by mixing of ligand with FeSO_4 in buffered solution in the presence of sodium ascorbate. All the iron complexes cleaved pUC 19 DNA efficiently and were found to cleave 281 base-pair DNA with a little selectivity, indicating that the dinuclear metal-chelating moiety that connected by the linker may be necessary for the sequence selectivity of DNA strand scission.

DNA切割试剂是治疗癌症和遗传性疾病必不可少的工具。期望能够选择性切割DNA特定序列和特定结构的试剂能够应用于抗肿瘤药物和人工限制性内切酶。在我开发能够同时和选择性地切割双链DNA的新型光学活性双核铁配合物的方法中，我制备了六种双核配体，(1,8-（N-蒽基甲基）-双(N‘，N’-二吡啶基甲基-（R，R）或（S，S）-环己烷-1,2-二胺（R或S- abdc）， 1,3-（N-木基甲基）-双(N‘，N’-二吡啶基甲基-（R，R）或（S，S）-环己烷-1,2-二胺（m-R-BDC或m-S-BDC），1,4-（N-基甲基）-双（N′，N′-二吡啶基甲基）- （R，R）或（S，S）-环己烷-1,2-二胺（p-R-DBC或p-S-BDC）。此外，研究了在抗坏血酸钠存在的缓冲溶液中，将配体与FeSO_4混合制备的铁配合物对质粒puc19 DNA的切割活性。所有的铁配合物都能有效地切割pUC 19 DNA，并能切割281碱基对DNA，但选择性很小，这表明由连接子连接的双核金属螯合片段可能是DNA链切割序列选择性所必需的。

项目成果

Synthesis and spectroscopic properties of a nickel(II) complex with a chiral N,N,N'-tri(2-pyridylmethyl)-S-2-(aminomethyl)piperidine = S-P3pipda

手性 N,N,N-三(2-吡啶甲基)-S-2-(氨甲基)哌啶 = S-P3pipda 镍(II)配合物的合成和光谱性质

• 发表时间: 2005
• 期刊: Inorg. Chem. Commun. 8
• 作者: K.Ohyama;et al.;Masayuki Yoshikawa et al.;Hiromasa Kurosaki
• 通讯作者: Hiromasa Kurosaki

Synthesis and spectroscopic properties of a nickel(II) complex with a chiral N,N,N-tri(2-pyridylmethyl)-S-2-(aminomethyl) piperidine=S-P3pipda

手性 N,N,N-三(2-吡啶甲基)-S-2-(氨甲基)哌啶=S-P3pipda 镍(II)配合物的合成及光谱性质

• 发表时间: 2005
• 期刊: Inorg.Chem.Commun. 8
• 作者: N.Kishikawa;et al.;Koyo Nishida;Hiromasa Kurosaki
• 通讯作者: Hiromasa Kurosaki

Mechanism of formation of iron(II) complexes with pentadentate ligands via C-C bond formation between trans-[Fe(2,4-bis(2-pyridyl methylimino)pentane(MeCN)_2][ClO_4]_2 MeCN and various nitriles

反式-[Fe(2,4-双(2-吡啶基甲基亚氨基)戊烷(MeCN)_2][ClO_4]_2 MeCN与各种腈之间形成C-C键形成五齿配体铁(II)配合物的机理

• 发表时间: 2005
• 期刊: Dalton Trans.
• 作者: N.Kuroda;et al.;Masayuki Yoshikawa et al.;Koyo Nishida;Hiromasa Kurosaki
• 通讯作者: Hiromasa Kurosaki

Synthesis, Characterization, and crystal structure of the copper(II) complex of the optical active polypyridylmethylamine ligand : N,N,N-tris(2-pyridylmethyl)-S-2-(aminomethyl)piperidine = S-P3pida

光学活性聚吡啶基甲胺配体的铜(II)配合物的合成、表征和晶体结构：N,N,N-三(2-吡啶基甲基)-S-2-(氨基甲基)哌啶 = S-P3pida

• 发表时间: 2004
• 期刊: Inorg.Chem.Commun. 7
• 作者: K.Ohyama;et al.;Masayuki Yoshikawa;Hiromasa Kurosaki
• 通讯作者: Hiromasa Kurosaki

Mechanism of formation of iron(II) complexes with pentadentate ligands via C-Cbond formation between trans-[Fe(2,4-bis(2-pyridylmethylimino)pentane(MeCN)_2][ClO_4]_2・MeCN and various nitriles

反式-[Fe(2,4-双(2-吡啶基甲基亚氨基)戊烷(MeCN)_2][ClO_4]_2·MeCN与各种腈之间形成C-C键与五齿配体形成铁(II)络合物的机理

• 发表时间: 2005
• 期刊: Dalton Trans.
• 作者: K.Ohyama;et al.;Masayuki Yoshikawa et al.;Hiromasa Kurosaki;Takashi Katsu;Koyo Nishida;Masayuki Yoshikawa et al.;Hiromasa Kurosaki
• 通讯作者: Hiromasa Kurosaki