Development of a new method for chemical synthesis of aminoacylated tRNA.

• Project/Area Number: 20750129
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemistry related to living body
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: OHKUBO Akihiro Tokyo Institute of Technology, 大学院・生命理工学研究科, 助教 (60376960)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: アミノシルtRNA / 核酸合成 / 保護基 / tRNA / 核酸 / 有機化学 / 高分子化学

Research Abstract

We developed a new method for the thermolytic deprotection of amidine-type protecting groups on nucleosides and nucleotides under acidic conditions using HOBt and IMT. Moreover, our new strategy allowed the first synthesis of an RNA oligomer carrying a base-labile acyl group on adenine. These results have prompted us to study the introduction of various artificial aminoacyl groups into RNA oligomers. These additional studies are now underway.

Research Products

• [Journal Article] Synthesis and hybridization properties of oligonucleotides incorporating Bi- and Tri-cyclic cytosine derivatives (2010)
  • Author(s): A. Ohkubo, T. Sakaue, H. Tsunoda, K. Seio, M. Sekine
  • Journal Title: Chem. Lett. (in press)
  • Peer Reviewed
• [Journal Article] Synthesis of oligodeoxynucleotides using the oxidatively cleavable 4-methoxytritylthio (MMTrS) group for protection of the 5 '-hydroxyl group (2010)
  • Author(s): K. Seio, M. Shiraishi, E. Utagawa, A. Ohkubo, M. Sekine;
  • Journal Title: New J. Chem. 34 Pages: 984-992
  • Peer Reviewed
• [Journal Article] Oligonucleotide synthesis involving deprotection of amidine-type protecting groups for nucleobases under acidic conditions (2010)
  • Author(s): A. Ohkubo, Y. Kuwayama, Y. Nishino, H. Tsunoda, K. Seio, M. Sekine
  • Journal Title: Org. Lett. 12 Pages: 2496-2499
  • Peer Reviewed
• [Journal Article] Linear relationship between deformability and thermal stability of 2 '-O-modified RNA hetero duplexes (2010)
  • Author(s): Y. Masaki, H.A. Ohkubo, K. Seio, M. Sekine
  • Journal Title: J. Phys. Chem. B. 114 Pages: 2517-2524
  • Peer Reviewed
• [Journal Article] Synthesis of 6-N( benzothiazol-2-yl)deoxyadenosine and its exciton-coupled circular dichroism (2010)
  • Author(s): Y. Masaki, H.A. Ohkubo, K. Seio, M. Sekine
  • Journal Title: Bioorg. Med. Chem. 18 Pages: 567-572
  • Peer Reviewed
• [Journal Article] Microwave-assisted synthesis of 2 '-O-aryluridine derivatives (2009)
  • Author(s): Y. Oeda, Y. Iijima, H. Taguchi, A. Ohkubo, K. Seio, M. Sekine
  • Journal Title: Org. Lett. 11 Pages: 5682-5585
  • Peer Reviewed
• [Journal Article] Synthesis and hybridization of 2'-O-methyl-RNAs incorporating 2'-O-carbamoyluridine and unique participation of the carbamoyl group in U-G base pair (2009)
  • Author(s): K. Seio, R. Tawarada, T. Sasami, M. Serizawa, M. Ise, A. Ohkubo, M. Sekine
  • Journal Title: Bioorg. Med. Chem 17 Pages: 7275-7280
  • Peer Reviewed
• [Journal Article] Synthesis and properties of nucleoside derivatives acylated by chemically stable 2-(trimethylsilyl)benzoyl group (2009)
  • Author(s): K. Yamada, H. Taguchi, A. Ohkubo, K. Seio, M.
  • Journal Title: Sekine; Bioorg. Med. Chem. 17 Pages: 5928-5932
  • Peer Reviewed
• [Journal Article] Fluorescence properties of pyrimidopyrimidoindole nucleoside dC(PPI) incorporated into oligodeoxynucleotides. (2009)
  • Author(s): M. Mizuta, K. Seio, A. Ohkubo, M. Sekine
  • Journal Title: J. Phys. Chem. B. 113 Pages: 9562-9569
  • Peer Reviewed
• [Journal Article] Efficient solid-phase synthesis of oligodeoxynucleotides having a 5'-terminal 2, 2, 7-trimethylguanosine pyrophosphate linkage (2009)
  • Author(s): A. Ohkubo, R. Kasuya, K. Aoki, A. Kobori, H. Taguchi, K. Seio, M. Sekine
  • Journal Title: Bioorg. Med. Chem. 17 Pages: 4819-4824
  • Peer Reviewed
• [Journal Article] Synthesis of terminally modified oligonucleotides and their hybridization dependence on the size of the target RNAs (2009)
  • Author(s): K. Seio, Y. Takaku, K. Miyazaki, S. kurohagi, Y. Masaki, A. Ohkubo, M. Sekine
  • Journal Title: Org. Biomol. Chem. 7 Pages: 2440-2451
  • Peer Reviewed
• [Journal Article] Introduction of 3 '-terminal nucleosides having a silyl-type linker into polymer supports without base protection (2009)
  • Author(s): A. Ohkubo, Y. Noma, K. Aoki, H. Tsunoda, K. Seio, Sekine
  • Journal Title: J. Org. Chem. 74 Pages: 2817-2823
  • Peer Reviewed
• [Journal Article] Synthesis and triplex formation of oligonucleotides containing 8-thioxodeoxyadenosine (2009)
  • Author(s): K. Miyata, R. tamamushi, H. Tsunoda, A. Ohkubo, K. Seio, M. Sekine
  • Journal Title: Org. Lett. 11 Pages: 605-608
  • Peer Reviewed
• [Journal Article] New thermolytic carbamoyl groups for the protection of nucleobases (2009)
  • Author(s): A. Ohkubo, R. Kasuya, K. Miyata, H. Tsunoda, K. Seio, M. Sekine
  • Journal Title: Org. Biomol. Chem. 7 Pages: 687-694
  • Peer Reviewed
• [Journal Article] Efficient solid-phase synthesis of oligodeoxynucleotides having a 5'-terminal 2,2,7-trimethylguanosine pyrophosphate linkage (2009)
  • Author(s): A.Ohkubo, R.Kasuya, K.Aoki, A.Kobori, H.Taguchi, K.Seio, M.Sekine
  • Journal Title: Bioorg.Med.Chem. 17 Pages: 7275-7280
  • Peer Reviewed
• [Journal Article] Fluorescence properties of pyrimidopyrimidoindole nucleoside dC(PPI)incorporated into oligodeoxynudeotides (2009)
  • Author(s): M.Mizuta, K.Seio, A.Ohkubo, M.Sekine
  • Journal Title: J.Phys.Chem.B 113 Pages: 9562-9569
  • Peer Reviewed
• [Journal Article] Microwave-assisted synthesis of 2'-O-aryluridine derivatives (2009)
  • Author(s): Y.Oeda, Y.Iijima, H.Taguchi, A.Ohkubo, K.Seio, M.Sekine
  • Journal Title: Org.Lett. 11 Pages: 5682-5585
  • Peer Reviewed
• [Journal Article] Introduction of 3'-terminal nucleosides having a silyl-type linker into polymer supports with out base protection (2009)
  • Author(s): Ohkubo A, Noma Y, Aoki K, Tsunoda H, Seio K, Sekine M
  • Journal Title: Journal of the Organic Chemistry 74 Pages: 2817-23
  • Peer Reviewed
• [Journal Article] New thermolytic carbamoyl groups for the protection of nucleobases (2009)
  • Author(s): Ohkubo A, Kasuya R, Miyata K, Tsunoda H, Seio K, Sekine M.
  • Journal Title: Organic & biomolecular chemistry 7 Pages: 687-694
  • Peer Reviewed
• [Journal Article] Hybridization-dependent fluorescence of oligodeoxynucleotides incorporating new pyrene-modified adenosine residues (2008)
  • Author(s): K. Seio, M. Mizuta, K. Tasaki, K. Tamaki, A. Ohkubo, M. Sekine
  • Journal Title: Bioorg. Med. Chem. 16 Pages: 8287-8293
  • Peer Reviewed
• [Journal Article] New nucleotide pairs for stable DNA triplexes stabilized by stacking interaction (2008)
  • Author(s): M. Mizuta, J. Banba, T. Kanamori, R. Tawarada, A. Ohkubo, M. Sekine, K. Seio
  • Journal Title: J. Am. Chem. Soc. 130 Pages: 9622-9623
  • Peer Reviewed
• [Journal Article] O-selective condensation using P-N bond cleavage in RNA synthesis without base protection (2008)
  • Author(s): A. Ohkubo, Y. Kuwayama, T. Kudo, H. Tsunoda, K. Seio, M
  • Journal Title: Org. Lett. 10 Pages: 2793-2796
  • Peer Reviewed
• [Journal Article] Efficient synthesis of functionalized oligodeoxyribonucleotides with base-labile groups using a new silyl linker (2008)
  • Author(s): A. Ohkubo, R. Kasuya, K. Aoki, A. Kobori, H. Taguchi, K. Seio, M.
  • Journal Title: Bioorg. Med. Chem. 16 Pages: 5345-5351
  • Peer Reviewed
• [Journal Article] "Protected DNA Probes (PDP)" capable of strong hybridization without removal of base protecting groups (2008)
  • Author(s): A. Ohkubo, R. Kasuya, K. Sakamoto, K. Miyata, H. Taguchi, H. Nagasawa, T. Tsukahara, T. Watanobe, Yoshiyuki Maki, Kohji Seio, Mitsuo Sekine
  • Journal Title: Nucleic Acids Res. 36 Pages: 1952-1964
  • Peer Reviewed
• [Journal Article] Synthesis and properties of DNA oligomers containing 2'-deoxynucleoside-N-oxide derivatives (2008)
  • Author(s): H. Tsunoda, A. Ohkubo, H. Taguchi, K. Seio, Sekine
  • Journal Title: J. Org. Chem. 73 Pages: 1217-1224
  • Peer Reviewed
• [Journal Article] Protected DNA Probes' capable of strong hybridization without removal of base protecting groups (2008)
  • Author(s): Ohkubo A, Kasuya R, Sakamoto K, Miyata K, Taguchi H, Nagasawa H, Tsukahara T, Watanobe T, Maki Y, Seio K, Sekine M.
  • Journal Title: Nucleic Acids Research 36 Pages: 1952-1964
  • Peer Reviewed
• [Presentation] 次世代のRNAテクノロジーを支える革新的核酸合成法の開発 (2010)
  • Author(s): 大窪章寛
  • Organizer: 日本化学会 第90回春季年会
  • Place of Presentation: 近畿大学(近畿大学)
  • Year and Date: 2010-03-27
• [Presentation] ホスホロアミダイト化合物を利用した新規ピロリン酸化反応の開発 (2010)
  • Author(s): 大窪章寛、西野雄大、角田浩佑、清尾康志、関根光雄
  • Organizer: 日本化学会第90春季年会
  • Place of Presentation: 近畿大学
  • Year and Date: 2010-03-26
• [Presentation] Synthesis and triplex formation of oligonucleotides containing 8-thioxodeoxyadenosine and 5-methyl-2-thiodeoxycytosine (2009)
  • Author(s): Akihiro Ohkubo, Kenichi Miyata, Hirosuke Tsunoda, Kohji Seio, Mitsuo Sekine
  • Organizer: 国際核酸医薬シンポジウム第5回OTS年会第19回アンチセンスシンポジウム合同シンポジウム
  • Place of Presentation: 九州大学
  • Year and Date: 2009-11-04
• [Presentation] Synthesis and triplex formation of oligonucleotides containing 8-thioxodeoxyadenosine and 5-methyl-2-thiodeoxycytosine (2009)
  • Author(s): Akihiro Ohkubo, Kenichi Miyata, Hirosuke Tsunoda, Kohji Seio, Mitsuo Sekine
  • Organizer: 第6回国際核酸化学シンポジウム
  • Place of Presentation: 岐阜県高山市民文化会館
  • Year and Date: 2009-09-28
• [Presentation] Evaluation of base recognition abilities of 2'-deoxynucleoside N-oxide derivatives by polymerase reactions (2009)
  • Author(s): Hirosuke Tsunoda, Akihiro Ohkubo, Kohji Seio, Mitsuo Sekine
  • Organizer: 第6回国際核酸化学シンポジウム
  • Place of Presentation: 岐阜県高山市民文化会館
  • Year and Date: 2009-09-28
• [Presentation] 末端にジリン酸結合を介してアデニル化されたオリゴヌクレオチドの効率合成法の開発 (2009)
  • Author(s): 大窪章寛、西野雄大、野間靖弘、桑山靖和、角田浩佑、清尾康志、関根光雄
  • Organizer: 第11回RNAミーティング
  • Place of Presentation: 朱鷺メッセ・新潟コンベンションセンター
  • Year and Date: 2009-07-28
• [Presentation] 機能性RNA分子の合成を指向した酸脱保護RNA合成法の開発 (2009)
  • Author(s): 桑山靖和、大窪章寛、西野雄大、角田浩佑、清尾康志、関根光雄
  • Organizer: 第11回RNAミーティング
  • Place of Presentation: 朱鷺メッセ・新潟コンベンションセンター
  • Year and Date: 2009-07-28
• [Presentation] Development of new methods for the synthesis of RNA oligonucleotides having base-labile functional groups (2008)
  • Author(s): 大窪章寛
  • Organizer: 18^<th> International roundtable on nucleosides, Nucleotides and Nucleic Acids
  • Place of Presentation: 京都大学
  • Year and Date: 2008-09-09
• [Remarks]
  • URL: http://www.skn.bio.titech.ac.jp/