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2019 Fiscal Year Final Research Report

Development of cell-permeable oligonucleotides bearing bio-cleavable protecting groups

Research Project

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Project/Area Number 17K01966
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical biology
Research InstitutionShiga University of Medical Science (2019)
Kanagawa University (2017-2018)

Principal Investigator

Hisao Saneyoshi  滋賀医科大学, 医学部, 助教 (10564784)

Project Period (FY) 2017-04-01 – 2020-03-31
Keywords保護基 / 細胞膜透過性 / 細胞内化学反応 / 活性化 / 合成核酸
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.

Free Research Field

核酸化学

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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Published: 2021-02-19  

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