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2023 Fiscal Year Final Research Report

Development of gene regulation techniques by selective modification of nucleic acid 3D structures.

Research Project

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Project/Area Number 19K05743
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionTokyo University of Agriculture and Technology

Principal Investigator

Tera Masayuki  東京農工大学, 工学(系)研究科(研究院), 准教授 (10643512)

Project Period (FY) 2019-04-01 – 2024-03-31
Keywordsグアニン四重鎖 / 核酸化学 / 光反応
Outline of Final Research Achievements

G-quadruplexes (G4) are higher-order structures found in single-stranded nucleic acids, particularly in gene promoter regions, and play a role in suppressing mRNA production. This study aimed to design a bifunctional ligand, 6OTD-Bp, recognizing both the G-quartet plane and the groove of G4 structures. Binding affinity and cross-linking ability were evaluated using thiazole orange (TO) displacement and UV irradiation experiments. Results showed that 6OTD-Bp specifically binds and cross-links to telomeric and hybrid G4s. NMR and MALDI-MS confirmed these interactions and cross-linking. This bifunctional approach enhances G4 recognition and stabilization, providing a new strategy for ligand design with higher selectivity for individual G4 structures.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究は、G-カルテット面とグルーブを同時に認識する二重認識リガンド6OTD-Bpを開発し、G4構造の認識と安定化の新たな戦略を提案したものである。この成果により、特異的なG4構造を標的とすることで、遺伝子発現の制御や新しい抗がん剤の開発に貢献する可能性がある。G4構造に対する理解が深まり、核酸化学および生物医学研究における重要な進展を示している。さらに、G4リガンドの設計が改良され、将来的にはさまざまな疾患の治療法開発にも役立つと期待される。

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Published: 2025-01-30  

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