Scientific research on triplex-forming oligonucleotides aiming at to develop next-generation of medicines

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460144
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Nagoya University
• Principal Investigator: Kodama Tetsuya 名古屋大学, 創薬科学研究科, 准教授 (00432443)
• Research Collaborator: MAKINO Ai ; HARA Takashi ; KONDA Tatsuya
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 人工核酸 / 構造制御 / 核酸化学 / 有機合成化学 / ヌクレオシド / 創薬化学

Outline of Final Research Achievements

We aimed to build a foundation for the next-generation of oligonucleotides drug including antigene technology by means of syntheses and evaluations of conformationally-restricted nucleosides. In this study, first, we synthesized novel nucleosides having a C4'-endo type sugar moiety or C3-endo type one. As a result of evaluating the triple-stranded oligonucleotides' stability, it was revealed that 2'-5' linked nucleic acid restricted to a C3-endo conformation, which was believed to destabilize the higher-order structure so far, can stably form a triplex did. Moreover, we clarified that the rotation angle around the glycosidic bond is a major factor determining the stability of the higher order structure by comparing the structure details of these artificial oligonucleotides with LNAs.

Free Research Field

ヌクレオシドの設計と合成、さらにそのオリゴ核酸中での機能性評価を基盤とした創薬化学