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Sequence specific double-strand DNA cleavage by an optical active dinuclear iron complex and application for artificial restriction enzyme

Sequence specific double-strand DNA cleavage by an optical active dinuclear iron complex and application for artificial restriction enzyme
光学活性双核铁复合物对序列特异性双链 DNA 的切割及其人工限制性内切酶的应用
批准号:
14572034
负责人:
KUROSAKI Hiromasa
金额:
$2.18万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2002
资助国家:
日本
项目状态:
已结题
起止时间:
2002 至 2003

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中文摘要
翻译
1-1)我的方法是创建金属复合体,该复合体能够完全和选择性地清除双链DNA(如bleomycin,哪种是一种抗生素或抗生素,它导致DNA在5'-GC-3'或5'-GT-3'位点上的单一和双链断裂),我准备了一种光学活性五聚氰胺配体, N,N,n'-tri(2-pyridylmethyl)-2-S-(氨基甲基)吡啶= S-P3吡啶从S-2-氨基吡啶的反应中获得,含有3个相等量的2-氯甲基吡啶,并研究铜(II)和镍(II)复合物的X射线晶体结构,[Cu](S-P3pipda)](ClO_4)_2和[Ni](S-P3 pipda)(OH_2)](ClO_4)_2复合体, [Cu](S-P3pipda)](ClO_4)_2和[Ni](S-P3pipda)(OH_2)](ClO_4)_2,were prepared from the reaction of an equimolar amount of Cu(ClO_4)_2·6H_2 O or Ni(SO_4)_2·6H_2 O(由LiClO_4的添加物)配体S-P3管在argon下的甲醇。[Cu]的X射线晶体结构(S-P3 pida)]^<2+>显示在两种第三胺中的三角形和正方形金字塔之间的中间结构,在两种第三胺中,equatrial position被占用。(N2 and N3) and two pyridine nitrogens (N1 and N4) and axial position by a pyridine nitrogen (N5)。渗透离子偶氮变弱: Cu-O是3.55.1 -2)我们合成了1,8-(N-羟基甲基)-二(N',N'-二酰甲基-R,R-环己酮-1,2-二胺), 1,并在空气中对1 DNA的清除活动进行了评估。一种新型的Fe复合体1和钠冷凝器系统清除了DNA丰富的A-T区域.(2)Moreover,我合成了两个新的核平台(II)复合体, 1,3-和1,4-(benzenedimethanethiolate-S)di(2,2',2'-terpyridine)platinum(II) chloride tetrahydrate (2 and 3), were synthesized in order to investigate the binding of platinum(II) complexes with calf thymus DNA,这些都是由紫外线和CD光谱学进行的。复合体2与DNA紧密相互作用,通过相互作用比较为3。
英文摘要
1-1)In my approach to create metal complexes that are capable of cleaving double-strand DNA simultaneously and sequence-selectively (like bleomycin, which is an antitumor antibiotic which causes single and double strand cleavage of DNA at 5'-GC-3' or 5'-GT-3' sites), I prepared an optical active pentadentate ligand, N,N,N'-tri(2-pyridylmethyl)-2-S-(aminomethyl)piperidine = S-P3pipda obtained from the reaction of S-2-aminopiperidine with 3 equimolar amounts of 2-chloromethylpyridine, and investigated the X-ray crystal structures of copper(II) and nickel(II) complexes of S-P3pipda, [Cu(S-P3pipda)](ClO_4)_2 and [Ni(S-P3pipda)(OH_2)](ClO_4)_2 Complexes, [Cu(S-P3pipda)](ClO_4)_2 and [Ni(S-P3pipda)(OH_2)](ClO_4)_2, were prepared from the reaction of an equimolar amount of Cu(ClO_4)_2・6H_2O or Ni(SO_4)_2・6H_2O (followed by addition of LiClO_4) with the ligand S-P3pipda in methanol under argon.The X-ray crystal structure of [Cu(S-P3pida)]^<2+> shows an intermediate structure between trigonal bipyramid and square pyramid in which equatrial positions are occupied by two tertiary amines (N2 and N3) and two pyridine nitrogens (N1 and N4) and axial position by a pyridine nitrogen (N5). Perchlorate ion coordinates weakly : Cu-O is 3.55 Å.1-2)We synthesized 1,8-(N-anthranylmethyl)-bis(N',N'-dipyridylmethyl-R,R-cyclohexane-1,2-diamine), 1, and cleaving activity of 1 to DNA was evaluated in the presence of sodium ascorbate under air. A novel Fe complex 1 and sodium ascorbate system cleaved A-T rich region of DNA.2)Moreover, I have synthesized two new dinuclear platinum(II) complexes, 1,3-and 1,4-(benzenedimethanethiolate-S)di(2,2',2"-terpyridine)platinum(II) chloride tetrahydrate (2 and 3), were synthesized in order to investigate the binding of platinum(II) complexes with calf thymus DNA, which was examined by UV and CD spectroscopies. Complex 2 interacted strongly with DNA by intercalation compared to 3.
期刊论文(15)
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Masafumi Goto, Yasuhiko Ohse, Sayuri Koga, Yuka Kudo, Rinko Kukihara, Hiromasa Kurosaki: "Preparations of Low-Spin Tetra Cyano Iron Complexes of N-Benzyl-1,2-ethanediamine and Its Oxidative Dehydrogenation : Isolation of the Intermediate with Monoimine Li
Masafumi Goto、Yasuhiko Ohse、Sayuri Koga、Yuka Kudo、Rinko Kukihara、Hiromasa Kurosaki:“N-苄基-1,2-乙二胺的低自旋四氰基铁配合物的制备及其氧化脱氢:用单亚胺锂分离中间体
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Hiromasa Kurosaki, Toshiaki Tawada, Satomi Kawasoe, Yoko Ohashi, Masafumi Goto: "Crystal Sturucture of Chloro{N-mercaptoethyl[bis(6-methyl-2-pyridyl-methyl)amine]}zinc(II) Complex"Anal. Sci.. 19. x27-x28 (2003)
Hiromasa Kurosaki、Toshiaki Tawada、Satomi Kawasoe、Yoko Ohashi、Masafumi Goto:“氯{N-巯基乙基[双(6-甲基-2-吡啶基-甲基)胺]}锌(II)络合物的晶体结构”分析。
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Masafumi Goto, Yuuichiro Yamamoto, Masamisu Sumimoto, Nobuhiro Tsuruda, Hiromasa Kurosaki: "Conformation of 2-Aminomethylpyrrolidine and 2-Aminomethylpiperidine in Ternary Platinum(II) Complexes : Regulation of Conformation of the Diamine by the Coexistin
Masafumi Goto、Yuuichiro Yamamoto、Masamisu Sumimoto、Nobuhiro Tsuruda、Hiromasa Kurosaki:“三元铂 (II) 配合物中 2-氨基甲基吡咯烷和 2-氨基甲基哌啶的构象:共存蛋白对二胺构象的调节
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Masafumi Goto: "Interaction of Binuclear Xylylthiolato(2,2',2"-terpyridine)platinum(II) Complexes with DNA"Bioorg.Med.Chem.Lett.. 13. 825-828 (2003)
Masafumi Goto:“双核二甲苯硫基(2,2,2”-三联吡啶)铂(II)复合物与DNA的相互作用”Bioorg.Med.Chem.Lett.. 13. 825-828 (2003)
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11
    Development of inhibitors based on the molecular structure and mechanism of substrate hydrolysis by metallo-beta-lactamases
    Development of fluorescent probes for metallo-beta-lactamase-producing Gram-negative bacteria
    • 批准号:
      24659054
    • 项目类别:
      Grant-in-Aid for Challenging Exploratory Research
    • 资助金额:
      $2.41万
    • 财政年份:
      2012
    • 负责人:
      KUROSAKI Hiromasa
    • 依托单位:
    Development of irreversible inhibitors forβ-lactam inactived enzyme, metallo-β-lactamase
    • 批准号:
      21590116
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $3.0万
    • 财政年份:
      2009
    • 负责人:
      KUROSAKI Hiromasa
    • 依托单位:
    Structure-based Design of Selective metallo-β-lactamase
    • 批准号:
      18390038
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $10.63万
    • 财政年份:
      2006
    • 负责人:
      KUROSAKI Hiromasa
    • 依托单位:
    海外基金