Artificial quadruplex formation by novel modified nucleic acids for chemical regulation of gene expression

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K17888
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bio-related chemistry
• Research Institution: Konan University
• Principal Investigator: FUJII Taiga 甲南大学, 先端生命工学研究所, 助教 (40735338)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 四重鎖 / 修飾核酸 / 遺伝子発現制御 / 分子間構造形成 / 熱力学的安定性 / 酸解離定数 / 水素結合 / 金属イオン

Outline of Final Research Achievements

Recently, regulation of gene expression by quadruplex formation of DNAs and RNAs had been reported, and relationship between the kinds of disease initiation and nucleic acid structures is beginning to be discussed. In this project, novel modified oligo nucleotides which recognize target genes specifically by formation of intermolecular quadruplex were developed in order to regulate gene expression artificially.
In the case of G-quadruplexes, developed modified oligo nucleotides enabled to control topologies and stability of the quadruplexes by their sequence design, and their controlling ability of gene expression by target specific formation of quadruplex was confirmed.
In the case of quadruplex of cytosines, we clarified the importance of interactions between loop bases for their thermodynamic stabilities. Although synthesized modified bases stabilized the quadruplex structures, the stabilization effect was not sufficient to control gene expression by the quadruplex formation.

Free Research Field

生体機能関連化学