Synthesis and properties of artificilal nucleic acids with spiroketal moiety based on the control of the conformation of sugar and phosphate backbone

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K18295
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bio-related chemistry; Drug development chemistry
• Research Institution: Tokushima Bunri University
• Principal Investigator: Osawa Takashi 徳島文理大学, 薬学部, 助教 (00783226)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 核酸化学

Outline of Final Research Achievements

Nucleic acids with spiroketal structure, which were simplified Tricyclic-LNA analogs based on the control of the conformation of sugar and phosphate backbone, were designed. Thymidine derivatives and 2'-O-methyl-5-methyluridine derivatives with spiroketal structure have been synthesized, respectively. The conformational analysis of synthesized thymidine derivatives by 1H NMR mesurements indicated that the conformation of sugar and phosphate backbone of 5'-S-isomer was similar to those of Tricyclic-LNA, as we expected.

Free Research Field

核酸化学

Academic Significance and Societal Importance of the Research Achievements

スピロケタール構造によって核酸糖部とリン酸部の配座を適切に固定できることを、世界で初めて見出した。さらに、本人工核酸は原料のチミジンや5-メチルウリジンから10工程と、従来の人工核酸と比較して大幅に短い工程数で合成できた。このことは、実用的な高機能性人工核酸を開発するという目標の達成を目指す上で、本研究成果の特筆すべき点である。また今後、スピロケタール型人工核酸が優れた相補鎖RNA結合能を有することを明らかにできれば、本研究の成果が高機能性人工核酸の新しい分子設計の基盤になる可能性が秘められている。