Development of cell-permeable oligonucleotides bearing bio-cleavable protecting groups
Project/Area Number |
17K01966
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Chemical biology
|
Research Institution | Shiga University of Medical Science (2019) Kanagawa University (2017-2018) |
Principal Investigator |
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
Keywords | 保護基 / 細胞膜透過性 / 細胞内化学反応 / 活性化 / 合成核酸 / プロドラッグ / 徐放性 / 発蛍光色素 / 細胞内導入 / 核酸医薬 / グルタチオン / 核酸合成化学 / 細胞内導入法 / 細胞内環境 |
Outline of Final Research Achievements |
Objective of this project is to develop synthetic oligonucleotides with high cell-membrane permeability and activatable property. In research period, glutathione-labile protecting groups for phosphodiester moiety in oligonucleotides were developed. Oligonucleotides modified with glutathione-labile protecting groups showed cell-membrane permeability without use of transfection reagent. The cell-membrane permeability increased depending on the number of protecting groups. Moreover the location of protecting groups was also influenced on the cellular uptake. Internalized oligonucleoides were activated and transformed into biologically active oligonucleotides.
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Academic Significance and Societal Importance of the Research Achievements |
本研究成果の学術的意義は、チオールによって速やかに除去されるリン酸ジエステル部位保護基を開発した点である。保護基を結合した合成核酸は、細胞膜透過性を示しただけではなく細胞内部での脱保護反応により活性化され機能を示した。これらの成果は、核酸を基盤構造とする細胞内部で機能するプローブ分子や医薬品などへの応用が期待される。
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Report
(4 results)
Research Products
(26 results)