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

Research Project

Project/Area Number 14572034
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionKumamoto University

Principal Investigator

KUROSAKI Hiromasa  Kumamoto University, Faculty of Medicinal and Pharmaceutical Sciences, Associate Professor, 大学院・医学薬学研究部, 助教授 (70234599)

Co-Investigator(Kenkyū-buntansha) GOTO Masafumi  Kumamoto University, Faculty of Medicinal and Pharmaceutical Sciences, Professor, 大学院・医学薬学研究部, 教授 (50080180)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsiron complex / DNA cleavage / optical active / electronic spectra / CD spectra / 過酸化水素 / 酸化反応 / ESR / CDスペクトル
Research Abstract

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.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Hiromasa Kurosaki: "Interaction of Binuclear Xylylthiolato(2,2',2"-terpyridine)platinum(II) Complexes with DNA"Bioorg.Med.Chem.Lett.. 13. 825-828 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiromasa Kurosaki: "DNA cleavage by pentadenate iron(II) complexes containing fluoro-substituted phenyl groups"Bioorg.Med.Chem.Lett.. 12. 201-203 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masafumi Goto, Katsutoshi Tanaka, Masamitsu Sumimoto, Hiromasa Mori, Hiromasa Kurosaki: "Preparation of Ternary Platinum(II) Complexes with N-(ω-Phenylalkyl)-1,2-ethanediamine and 2,2'-Dipyridine and the Effect of the Methylene Chain Length of the N-(ω-Phenylalkyl)-1,2-ethanediamine in the Complexes on Intermolecular Interactions with Various Arylslfonates"Chem.Pharm.Bull.. 51(6). 649-653 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 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 Coexisting Ligand"Chem.Pharm.Bull.. 51(10). 1157-1162 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 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)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masafumi Goto, Hisashi Tsutsui, Syuuichi Matsuda, Yoshitomo Tanaka, Nobuhiro Tsuruda, Hiromasa Kurosaki: "Structures of Platinum(II) Complexes of 2-Aminomethylaziridine and S-2-Aminomethylazetidine and Correlation of Anticancer Activities of (2-Aminomethylazacycloalkane)platinum(II) Complexes with the Geometry of the Chilate Rings Formed with Platinum(II)"Chem.Pharm.Bull.. 52(1). 47-50 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 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 Ligand"Cull.Chem.Soc.Jpn. 77(5)(印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masafumi Goto: "DNA Cleavage by Pentadentate Iron(II) Complexes Containing Fluoro-Substituted Phenyl Groups"Bioorg. Med. Chem. Lett.. 12. 201-203 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masafumi Goto: "Detection of a metallo-β-lactamase (IMP-1) by fluorescent probes having dansyll and thiol groups"Org. Biomol. Chem.. 1. 17-20 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masafumi Goto: "Crystal Structure of 7,8-Dihydroxy-4-methylcoumarin"Anal. Sci.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masafumi Goto: "Interaction of Binuclear Xylylthiolato(2,2',2"-terpyridine)platinum(II) Complexes with DNA"Bioorg. Med. Chem. Lett.. 13. 825-828 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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