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Development of selective binding and cleavage ligands for the AP sites

Research Project

Project/Area Number 26860079
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionKyushu University

Principal Investigator

Abe Yukiko  九州大学, 薬学研究院, 助教 (40586856)

Project Period (FY) 2015-03-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywordsb-脱離 / 抗がん作用増強 / DNA脱塩基部位 / APサイト修復 / β-脱離
Outline of Final Research Achievements

DNA is continuously damaged by endogenous and exogenous factors. In the base excision repair pathway, the damaged nucleobases are removed by DNA N-glycosylase to form AP sites. The AP site is representative DNA damage and the alkylating antitumor agents exhibit cytotoxicity through the formation of the AP site. Therefore blockage or modulation of the AP site repair pathway may enhance the antitumor efficacy of DNA alkylating agents. We studied the effects of nucleobase-polyamine conjugates (G-, A-ligands), which specifically bind and cleave at the AP site, on the potentiation of the cytotoxicities by the alkylating agents. In the combined application of the ligand and DNA alkylating agents MMS, the G- and A-ligands showed the potential of the enhancement of antitumor efficacy. Therefore we designed and synthesized the new ligand having the high affinity and cleavage activity to AP sites.The new ligand showed the affinity to the AP sites but have only a modest ceavage activity.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (2 results)

All 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] DNA cleavage at the AP site via β-elimination mediated by the AP site-binding ligands2016

    • Author(s)
      Yukiko S. Abe, Shigeki Sasaki
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 24 Issue: 4 Pages: 910-914

    • DOI

      10.1016/j.bmc.2016.01.016

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] DNA cleavage at the AP site by nucleobase-polyamine conjugates2016

    • Author(s)
      Yukiko Abe, Shigeki Sasaki
    • Organizer
      The 43rd International Symposium on Nucleic Acids Chemistry 2016
    • Place of Presentation
      100th Anniversary Hall, Kumamoto University
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2019-07-29  

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