Development of a pinpoint functionalization method of nucleic acids

• Project/Area Number: 17K05943
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Tokushima Bunri University
• Principal Investigator: Hari Yoshiyuki 徳島文理大学, 薬学部, 教授 (50347423)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: コンジュゲートオリゴ核酸 / オリゴ核酸上の化学反応 / 有機化学 / 核酸化学

Outline of Final Research Achievements

In this research, iridium-conjugated oligonucleotides were synthesized and we found that the conjugated oligonucleotides could deiodinate (reduce) target oligonucleotides including iodouracil bases. Oligonucleotides bearing acylthio groups were also synthesized and it was achieved that acyl transfer from the acylthio group to the amino group of a target oligonucleotide where aminomethyluracil bases are contained. Moreover, the position suitable for acyl transfer was examined.

Academic Significance and Societal Importance of the Research Achievements

狙った核酸の望みの位置の核酸塩基のみをピンポイントで直接的に官能基化することができれば、既存の機能性オリゴ核酸の更なる機能性向上や期待できます。本研究成果はそれを実現するためのはじめの一歩となる研究です。本研究で開発した可視光照射により酸化還元能を示すイリジウム連結オリゴ核酸やアシル基転位能を有する活性エステル連結オリゴ核酸は他の技術への応用も期待でき、今後の核酸化学研究の発展に寄与することが考えられます。

Research Products

• [Journal Article] Synthesis and hybridization properties of iridium(III) polypyridyl complex-conjugated oligonucleotide (2020)
  • Author(s): Yuta Ito, Koichi Mizuno, Kohei Domoto, Yoshiyuki Hari
  • Journal Title: Nucleos. Nucleot. Nucleic Acids Volume: 39 Issue: 1-3 Pages: 69-81
  • DOI: 10.1080/15257770.2019.1690150
  • Peer Reviewed
• [Journal Article] Triplex- and Duplex-Forming Abilities of Oligonucleotides Containing 2′-Deoxy-5-trifluoromethyluridine and 2′-Deoxy-5-trifluoromethylcytidine (2017)
  • Author(s): Y. Ito, M. Matsuo, T. Osawa, Y. Hari
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 65 Issue: 10 Pages: 982-988
  • DOI: 10.1248/cpb.c17-00530
  • NAID: 130006109934
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Open Access
• [Presentation] Synthesis of iridium-conjugated oligonucleotides and their application (2019)
  • Author(s): 伊藤勇太，堂本晃平，大澤昂志，張 功幸
  • Organizer: 日本核酸医薬学会第5回年会
• [Presentation] イリジウム錯体を導入したオリゴ核酸の合成とその応用 (2019)
  • Author(s): 堂本晃平，伊藤勇太，大澤昂志，張 功幸
  • Organizer: 第2回 日本核酸化学会 中四国地区セミナー
• [Presentation] イリジウム錯体コンジュゲートオリゴ核酸の合成 (2019)
  • Author(s): 堂本晃平，伊藤勇太，大澤昂志，張 功幸
  • Organizer: 日本薬学会第139年会
• [Presentation] イリジウム錯体コンジュゲートオリゴ核酸の合成 (2019)
  • Author(s): 堂本晃平、伊藤勇太、大澤昂志、張 功幸
  • Organizer: 日本薬学会第139年会