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2005 Fiscal Year Final Research Report Summary

Molecular Design of Drugs recognizing Trinucleotide Repeat Sequence.

Research Project

Project/Area Number 15201042
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied genomics
Research InstitutionOsaka University (2005)
Kyoto University (2003-2004)

Principal Investigator

NAKATANI Kazuhiko  Osaka University, The Institute of Scientific and Industrial Research, Professor, 産業科学研究所, 教授 (70237303)

Co-Investigator(Kenkyū-buntansha) ZHOU Da-Yang  Osaka University, The Institute of Scientific and Industrial Research, Research Associate, 産業科学研究所, 助手 (00324848)
HAGIHARA Masaki  Osaka University, The Institute of Scientific and Industrial Research, Research Associate, 産業科学研究所, 助手 (40403000)
TAKEI Fumie  Osaka University, The Institute of Scientific and Industrial Research, Technical Staff, 産業科学研究所, 教務職員 (30252711)
Project Period (FY) 2003 – 2005
KeywordsTrinucleotide Repeat / Genetic Disease
Research Abstract

DNA trinucleotide repeats, particularly CXG, are common within the human genome. However, expansion of trinucleotide repeats is associated with a number of disorders, including Huntington's disease, spinobulbar muscular atrophy, and spinocerebellar ataxia1-4. In these cases, the repeat length is known to correlate with decreased age of onset and disease severity5,6. Repeat expansion of (CAG)n, (CTG)n, and (CGG)n trinucleotides may be related to the increased stability of alternative DNA hairpin structures consisting of CXG/CXG triads with X-X mismatches7-11. Small molecule ligands that selectively bound to CAG repeats could provide an important probe for determining repeat length and an important tool for investigating the in vivo repeat extension mechanism. Here we report that naphthyridine-azaquinolone (NA,1) is a ligand for CAG repeats and can be used as a diagnostic tool for determining repeat length. We show by NMR spectroscopy that binding of NA to CAG repeats induces extrusion of a cytidine nucleotide from the DNA helix.

  • Research Products

    (2 results)

All 2005

All Journal Article (2 results)

  • [Journal Article] Small-molecule ligand induces nucleotide flipping in (CAG)n trinucleotide repeats2005

    • Author(s)
      K.Nakatani, C.Kojima et al.
    • Journal Title

      Nature Chemical Biology 1・1

      Pages: 43

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Small-molecule ligand induces nucleotide flipping in (CAG)n trinucleotide repeats,2005

    • Author(s)
      K.Nakatani, C.Kojima et al.
    • Journal Title

      Nature Chemical Biology 1(1)

      Pages: 43

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2007-12-13  

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