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Efficient translocation of hybrid peptides through cell membrane for the control of transcription

Research Project

Project/Area Number 10671987
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

FUTAKI Shiroh  Kyoto University, Institute for Chemical Research, Associate Professor, 化学研究所, 助教授 (50199402)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordscell-permeable peptide / synthetic peptide / HIV-1 Tat / NF-kappaB / IkappaB / iNOS / transcription factor / RNA-binding peptide / 細胞内導入 / ドラッグデリバリー / ペプチド工学 / ハイブリダイゼーション / 細胞内情報伝達 / 一酸化チッ素合成酵素
Research Abstract

Several methods for the introduction of peptides and proteins into mammalian cells have been developed with the hopes of understanding intracellular signal transudation mechanisms and applying these techniques for therapeutic uses. Among them, methods using basic peptides as carriers seem promising. Two peptides derived from HIV-1 Tat protein (48-60) and Antennapedia homeodomain protein (43-58) have been reported as cell permeable peptides. We have compared the translocation activity of these peptides using mouse macrophage RAW 264.7 cells. Cellular uptake and intracellular distribution of the peptides labeled with maleimido fluorescein diacetate were observed by fluorescence microscopy, and the former peptide was judged to have a superior activity. Other related peptides, such as the D-substituted analog and the Arg-substituted analogs of the Tat peptide were also found to be cell-permeable, which implied the applicability of these peptides to the peptide carriers. As an application of Tat (48-60) to the intracellular delivery of synthetic peptides, a hybrid peptide of Tat (48-60) and IκBα(15-49) was synthesized. IκBα is an inhibitory protein of a transcription factor NF-κB. Phosphorylation in its N-terminal domain leads the activation of NF-κB. The hybrid peptide was efficiently delivered into the cells within 3 h, indicative of the usefulness of Tat (48-60) as a peptide carrier. Intracellular delivery mediated by other Tat-related peptides was also investigated.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (5 results)

All Other

All Publications (5 results)

  • [Publications] S.Futaki、他: "Peptide Science 1999"Protein Research Foundatiom. 4 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shiroh Futaki, Tomoki Suzuki, Wakana Ohashi, Takeshi Yagami, Seigo Tanaka, Kunihiro Ueda, Yukio Sugiura: "INTRACELLULAR DELIVERY OF SYNTHETIC PEPTIDES MEDIATED BY TAT-RELATED PEPTIDES"Peptide Science. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Futaki, 他: "Peptide Science 1999"Protein Research Foundation. 4 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 二木 史朗: "蛋白質機能解明と機能創出を目指したペプチド合成" 薬学雑誌. 118巻11号. 493-510 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tachibana ら: "In trace llular Regulation of Macromolecules Using pH-Sensitwe liposomes and Nuclear Localization Signal" Biochem.Biophys Res.Commun. 251巻2号. 538-544 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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