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Molecular design of amphiphiles with DNA transfer ability into cell

Research Project

Project/Area Number 04558023
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 物質生物化学
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

ITO Akio  Kyushu University, Faculty of Science, Professor, 理学部, 教授 (30037379)

Co-Investigator(Kenkyū-buntansha) FUKUMOTO Takanori  Fukuoka Industrial Technology Center, Researcher., 主任研究員
AKAO Tetsuyuki  Fukuoka Industrial Technology Center, Researcher., 主任研究員
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1992: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsSynthetic bilayr membrane / Liposome / DNA transfection / DNA-liposome interaction / リポソ-ム
Research Abstract

Cationic amphiphiles which have aquaternary ammonium head, hydrocarbon tailsanda glutamic acid connector with methylenespacer have been used for delivery ofDNA into eukaryotic cells. we studied thecorrelation between the efficiency ofvarious cationic amphiphiles in DNA transfection and their physicochemical properties
1.We found that one of dialkyl ammonium amphiphile, didodecyl N- [ p- ( 2-trimethylammonioethoxy ) benzoyl ] -L-glutamate bromide, had a higher DNA transfection than commercially available lipid, DOTMA,and that there was a good correlation between their efficiencies in gene transfer and physicochemical characteristics.Amphiphilic compounds tthe phase transition temperatures ( Tc )of which are lower than the culture temperature and which form small stable vesicles are good carriers of DNA into cultured cells.
2.The result makes it possible to design compounds with a more efficient DNA transfection ability, and we designed and obtained a new cationic amphiphile with higher activity.
3.We investigated interaction the structural between cationic amphiphilesandDNA,bymeans of electron microscopy, CDandNMRspectroscopies, and fluoroscopy. Amphiphiles with phenylene in the spacer regionare restricted their mobility by bindingwith DNA while others are flexibleenough for arranging along DNA helix. Ontheother hand, conformation of DNA is forced to change by bilayr-forming amphiphiles at lower temperature than their Tc's.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] 赤尾哲之: "Design of a New Cationic Amphiphiles with Efficient DNA-Transfection Ability" Biochem.Mol.Biol.Int.34. 915-920

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 赤尾哲之: "Effect of DNA on the Stacking and Mobility of Cationic Bilayer-forming Amphiphiles." Biochemistry. (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 赤尾哲之: "Conformational Change of DNA Induced by Cationic Bilayer Membranes." Biochemistry. (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] T,Akao, T.Nakayama, K.Takeshita &A.Ito: "Design of a New Cationic Amphiphiles with Efficient DNA-Transfection Ability." Biochem.Mol.Biol.Int.34. 915-920 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] T.Akao, T.Fukumoto&A.Ito: "Effect of DNA on the Stacking and Mobility of Cationic Bilayr-forming Amphiphiles." Biochemistry. ( submitted ).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] T.Akao, T.Fukumoto, H.Ihara &A,Ito: "Conformational Change of DNA Induced by Cationic Bilayr Membranes." Biochemistry. ( submitted ).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary

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Published: 1992-04-01   Modified: 2016-04-21  

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