• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of peptide vectors containing Aid residues for gene therapy

Research Project

Project/Area Number 18590111
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionOsaka University of Pharmaceutical Sciences

Principal Investigator

WADA Shun-ichi  Osaka University of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Lecturer (30278593)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsPeptide-derived vector / DNA / oligonucleotide / α-aminoisobutyric acid / Aib / peptaibol
Research Abstract

The TV-XIIa-derived peptide vector [Ac-U-N-I-I-U-P-L-L-U-P-I-K-K-K-K-K-K-K-K-K-OH; Ac: acetyl, U: α-aminoisobutyric acid (Aib)], which is conjugated between TV-XIIa and a 10-mer of lysine (Lys), could deliver 20-mer oligonucleotides (ODN) into cells, and the 10-mer of Lys alone was not capable of delivering them. Then, TV-XIIa itself is consider to be an important role in the delivery system. To obtain the direct evidences for the cellular uptake of TV-XIIa itself and investigate the delivery principles of the 20-mer oligonucleotides, a fluorescein-labeled peptide with the TV-XIIa amino acid sequence was synthesized and applied to living cells to directly observe the behavior of TV-XIIa itself in living cells. Furthermore, to understand the importance of the three unusual Aib residues in the sequence, they were replaced with Ala, and the behavior of the Aib→Ala substitutional analog in living cells was also examined. The results indicated that the fluorescein-labeled TV-XIIa peptide can translocate into cells and the all replacement of Aib with Ala inhibits the cellular uptake. The translocation of the Aib-containing peptide seems to involve an energy-independent process. To optimize the 10-mer of lysine added as a ODN interaction part to TV-XIIa, the C-terminal moiety of the TV-XIIa-derived peptide vector was shortened to 8-, 6-, and 4-mers of Lys. The 4- and 6-mer derivatives cannot delivery ODNs into cells, on the other hand, the 8- and 10-mer derivatives significantly promote the uptake of ODNs. These results indicated that both the membrane permeability of TV-XIIa and the number of Lys residues might be important rolls to delivery the ODNs into cells
Next, amphiphatic 24-residual helix peptides [Ac-(U-U-U-K)6-NH2 and Ac-(U-U-K)8-NH2] were synthesized using a hydrophobic amino acid, Aib and a basic one, Lys. We found that the complexes, which were formed via electric-interaction between the helix peptides and ODNs, are taken up into cells.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (13 results)

All 2008 2007

All Journal Article (5 results) (of which Peer Reviewed: 2 results) Presentation (8 results)

  • [Journal Article] Translocation of an Aib-containing Peptide through Cell Membranes2008

    • Author(s)
      和田 俊一
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Translocation of an Aib-containing Peptide through Cell Membranes2008

    • Author(s)
      Shun-ichi Wada, Yasunari Hitora, Reiko Tanaka, Hidehito Urata
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Functionalized 20-Residual Peptaibol for Nucleic Acid Delivery2007

    • Author(s)
      和田 俊一
    • Journal Title

      Chemistry & Biodiversity 4

      Pages: 991-997

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Functionalized 20-Residual Peptaibol for Nucleic Acid Delivery2007

    • Author(s)
      Shun-ichi Wada and Reiko Tanaka
    • Journal Title

      Chemistry & Biodiversity 4(5)

      Pages: 991-997

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Functionalized 20-Residual Peptaibol for Nucleic Acid Delivery2007

    • Author(s)
      Shun-ichi Wada(和田俊一)
    • Journal Title

      Chemistry & Biodiversity 4・5

      Pages: 991-997

    • Related Report
      2006 Annual Research Report
  • [Presentation] Aib含有ペプチドTV-XIIaとその類縁体の細胞膜透過性研究2008

    • Author(s)
      和田 俊一
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Wada Membrane permeability of Aib-containing peptide, TV-XIIa and its derivative2008

    • Author(s)
      Shun-ichi
    • Organizer
      The 128th Annual Meeting of the Pharmaceutical Society of Japn
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2008-03-26
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Aib含有ペプチドTV-XIIaとその類縁体の細胞膜透過性研究2008

    • Author(s)
      和田 俊一
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2008-03-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] Aib含有ペプチドの膜透過性に関する研究2007

    • Author(s)
      和田 俊一
    • Organizer
      第57回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪
    • Year and Date
      2007-10-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Wada Membrane permeability of Aib-containing peptides2007

    • Author(s)
      Shun-ichi
    • Organizer
      The 57th Annual Meeting of the Pharmaceutical Society of Japn Kinki-branch
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2007-10-27
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Aib含有ペプチドの膜透過性に関する研究2007

    • Author(s)
      和田 俊一
    • Organizer
      第57回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪薬科大学(大阪府高槻市)
    • Year and Date
      2007-10-27
    • Related Report
      2007 Annual Research Report
  • [Presentation] Aib含有ペプチドを用いたオリゴヌクレオチドの細胞内導入2007

    • Author(s)
      和田 俊一
    • Organizer
      日本薬学会第127年会
    • Place of Presentation
      富山
    • Year and Date
      2007-03-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Wada Delivery of oligonucleotides into cells by Aib-containing peptides2007

    • Author(s)
      Shun-ichi
    • Organizer
      The 127th Annual Meeting of the Pharmaceutical Society of Japn
    • Place of Presentation
      Toyama, Japan
    • Year and Date
      2007-03-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi