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Cell-biological analysis of sequence-specific DNA alkylating molecules.

Research Project

Project/Area Number 20710164
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Living organism molecular science
Research InstitutionKyoto University

Principal Investigator

KEN-ICHI Shinohara  Kyoto University, 大学院・理学研究科, 助教 (70378561)

Co-Investigator(Renkei-kenkyūsha) BANDO Toshikazu  京都大学, 大学院・理学研究科, 准教授 (20345284)
SUGIYAMA Hiroshi  京都大学, 大学院・理学研究科, 教授 (50183843)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsテロメア / 核酸 / Py-Imポリアミド / 細胞老化 / DNAアルキル化 / PIポリアミド / 白血病
Research Abstract

We designed and synthesized alkylating N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates. The effects on telomere shortening and growth inhibition were investigated using human cancer cell lines. In addition, we modified the DNA alkylating moiety CBI to the chlorambucil, which are easier to synthesize from commercially available components. The sequence-specific DNA alkylations by the chlorambucil conjugates were observed, which were as efficient as their of the CBI conjugates. The chlorambucil conjugates recognized 11 bp of telomere sequence specifically. However, the growth inhibiting activities were relatively reduced compared with CBI conjugates. Thus, these low-toxic and highly efficient DNA alkylating molecules should be more useful for investigation of their gene regulating activities and study of DNA-damage responses.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (20 results)

All 2010 2009 2008 Other

All Journal Article (16 results) (of which Peer Reviewed: 6 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] Cell Permeability of Py-Im Polyamide - Fluorescein Conjugates: Influence of Molecular Size and Py/Im Content.2010

    • Author(s)
      Nishijima, S; Shinohara, K.; Bando, T.; Minoshima, M.; Kashiwazaki, G.; Sugiyama, H.
    • Journal Title

      Bioorg. Med. Chem. vol.18

      Pages: 978-983

    • Related Report
      2009 Final Research Report
  • [Journal Article] Potent Activity against K562 Cells by Polyamide - seco -CBI Conjugates Targeting Histone H4 Genes.2010

    • Author(s)
      Minoshima, M.; Chou, J.C.; Lefebvre, S.; Bando, T.; Shinohara, K.; Gottesfeld, J.M.; Sugiyama, H.
    • Journal Title

      Bioorg. Med. Chem. vol.18

      Pages: 168-174

    • Related Report
      2009 Final Research Report
  • [Journal Article] Anticancer Activities of Alkylating Pyrrole-Imidazole Polyamides with Specific Sequence Recognition.2010

    • Author(s)
      Shinohara, K.; Bando, T.; Sugiyama, H.
    • Journal Title

      Anti - Cancer Drug vol.21

      Pages: 228-242

    • Related Report
      2009 Final Research Report
  • [Journal Article] Comparative Analysis of DNA Alkylation by Conjugates between Pyrrole-Imidazole Hairpin Polyamides and Chlorambucil or seco-CBI.2010

    • Author(s)
      Minoshima, M.; Bando, T.; Shinohara, K.; Kashiwazaki, K.; Nishijima, S.; Sugiyama, H.
    • Journal Title

      Bioorg. Med. Chem. vol.18

      Pages: 1236-1243

    • NAID

      120001887644

    • Related Report
      2009 Final Research Report
  • [Journal Article] Chiral Wedge Molecule inhibits Telomerase Activity.2010

    • Author(s)
      Shinohara, K.; Sannohe, Y.; Kaieda, S.; Tanaka, K.; Osuga, H.; Xu, Y.; Bando, T.; Sugiyama, H.
    • Journal Title

      J. Am. Chem Soc. vol.132

      Pages: 3778-3782

    • Related Report
      2009 Final Research Report
  • [Journal Article] Alkylation of a Human Telomere Sequence by Heterotrimeric Chlorambucil PI Polyamide Conjugates.2010

    • Author(s)
      Kashiwazaki, G.; Bando, T.; Shinohara, K.; Mioshima, M.; Kumamoto, H.; Nishijima, S.; Sugiyama, H.
    • Journal Title

      Bioorg. Med. Chem. vol.18

      Pages: 2887-2893

    • Related Report
      2009 Final Research Report
  • [Journal Article] Anticancer Activities of Alkylating Pyrrole-Imidazole Polyamides with Specific Sequence Recognition2010

    • Author(s)
      Ken-ichi Shinohara, Toshikazu Bando, Hiroshi Sugiyama
    • Journal Title

      Anti-Cancer Drug 21

      Pages: 228-242

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alkylation of a human telomere sequence by heterotrimeric chlorambucil PI polyamide conjugates.2010

    • Author(s)
      Gengo Kashiwazaki, Toshikazu Bando, Ken-ichi Shinohara, Masafumi Minoshima, Hana Kumamoto, Shigeki Nishijima, Hiroshi Sugiyama
    • Journal Title

      Bioorganic & Medicinal Chemistry 18

      Pages: 2887-2893

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chiral wedge molecule inhibits telomerase activity2010

    • Author(s)
      Ken-ichi Shinohara, Yuta Sannohe, Shuji Kaieda, Ken-ichi Tanaka, Hideji Osuga, Hidetoshi Tahara, Yan Xu, Takashi Kawase, Toshikazu Bando, Hiroshi
    • Journal Title

      Journal of the American Chemical Society 132

      Pages: 3778-3782

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cooperative Alkylation of Double-strand Human Telomere Repeat Sequences by PI Polyamides with 11-Base-pair Recognition Based on a Heterotrimeric Design.2009

    • Author(s)
      Kashiwazaki, G. Bando, T.; Shinohara, K.; Minoshima, M.; Nishijima, S.; Sugiyama, H.
    • Journal Title

      Bioorg. Med. Chem. vol.17

      Pages: 1393-1397

    • Related Report
      2009 Final Research Report
  • [Journal Article] Synthesis and Properties of Polyamide - SAHA Conjugate.2009

    • Author(s)
      Ohtsuki, A.; Kimura, M.T.; Minoshima, M.; Suzuki, T.; Ikeda, M.; Bando, T.; Nagase, H.; Shinohara, K.; Sugiyama, H.
    • Journal Title

      Tetrahedron Lett. vol.50

      Pages: 7288-7292

    • Related Report
      2009 Final Research Report
  • [Journal Article] Cooperative Alkylation of Double-strand Human Telomere Repeat Sequences by PI Polyamides with 11-Base-pair Recognition Based on a Heterotrimeric Design2009

    • Author(s)
      Kashiwazaki, G. Bando, T. ; Shinohara, K. ; Minoshima, M. ; Nishijima, S. ; Sugiyama, H.
    • Journal Title

      Bioorganic Medicinal Chemistry 17

      Pages: 1393-1397

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of Triplet Repeat Sequences in the Double - Stranded DNA using Pyrene - Functionalized Pyrrole - Imidazole Polyamides with Rigid Linkers.2008

    • Author(s)
      Fujimoto, J.; Bando, T.; Minoshima, M.; Uchida, S.; Iwasaki, M.; Shinohara, K.; Sugiyama, H.
    • Journal Title

      Bioorg. Med. Chem. vol.16

      Pages: 5899-5907

    • Related Report
      2009 Final Research Report
  • [Journal Article] Perylene - Conjugated Pyrrole Polyamide as a Sequence-Specific Fluorescent Probe.2008

    • Author(s)
      Fujimoto, J.; Bando, T.; Minoshima, M.; Kashiwazaki, G.; Nishijima, S.; Shinohara, K.; Sugiyama, H.
    • Journal Title

      Bioorg. Med. Chem. vol.16

      Pages: 9741-9744

    • Related Report
      2009 Final Research Report
  • [Journal Article] Stable Lariat Formation Based on a G-quadruplex Scaffold2008

    • Author(s)
      Xu, Y. ; Sato, H. ; Sannohe, Y. ; Shinohara, K. : Sueivama. H.
    • Journal Title

      Journal of the American Chemical Society 130

      Pages: 16470-16471

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perylene-Conjugated Pyrrole Polyamide as a Sequence-Specific Fluorescent Probe2008

    • Author(s)
      Fujimoto, J. ; Bando, T. ; Minoshima, M. ; Kashiwazaki, G. ; Nishijima, S. ; Shinohara. K. ; Sugiyama, H.
    • Journal Title

      Bioorganic & Medicinal Chemistry 16

      Pages: 9741-9749

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Chiral wedge molecule inhibits telomerase activity2009

    • Author(s)
      篠原憲一
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜パシフィコ横浜
    • Year and Date
      2009-12-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Chiral wedge molecule inhibits telomerase activity2009

    • Author(s)
      篠原憲一、三戸祐太、大須賀秀次、徐岩、杉山弘
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] テロメアを標的とするピロール-イミダゾールポリアミド2008

    • Author(s)
      篠原憲一、板東俊和、杉山弘
    • Organizer
      第12回がん分子標的治療研究会総会
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Remarks]

    • URL

      http://kuchem.kyoto-u.ac.jp/chembio/

    • Related Report
      2009 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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