Development of artificial aromatic nucleic acid with cell membrane permeability

Research Project

Project/Area Number	24659045
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Single-year Grants
Research Field	Drug development chemistry
Research Institution	Gifu University
Principal Investigator	UENO Yoshihito 岐阜大学, 応用生物科学部, 教授 (20250467)
Project Period (FY)	2012-04-01 – 2014-03-31
Project Status	Completed (Fiscal Year 2013)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	アンチセンス核酸 / 細胞膜透過性 / ヌクレアーゼ耐性 / RNA親和性 / DNA二重鎖 / RNA二重鎖 / 熱力的安定性 / 熱力学的安定性 / ベンゼン / 二重鎖形成 / 熱的安定性 / 塩基識別能 / 人工核酸 / DNA / RNA / 核酸医薬 / 遺伝子
Research Abstract	The purpose of this study is development of artificial aromatic nucleic acid with cell membrane permeability which involves a benzene ring instead of a ribose ring. (S)-mandelic acid was used as a starting material. After esterification, iodization, reduction, and silylation, it was converted to a boronic acid derivative. Coupling reaction of it with an adenine or cytosine in the presence of cupper (II) produced adenine and cytosine analogs in good yields. It was found that the analogs reduced thermal stabilities of DNA/DNA and DNA/RNA duplexes, but the analogs possessed high base discrimination abilities.