Chemically modified DNAs cotrolled by triplex forming oligodeoxynucleotides

• Project/Area Number: 26288075
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Seio Kohji 東京工業大学, 生命理工学院, 准教授 (20313356)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: 三重鎖DNA / 人工遺伝子 / 蛍光核酸 / DNA三重鎖 / 合成生物学 / 核酸 / 有機化学 / 三重鎖核酸 / 三重鎖形成核酸 / 人工塩基 / 人工塩基対

Outline of Final Research Achievements

We developed artificial DNAs whose function could be controlled by triplex formation. First we developed artificial genes incorporating pseudouracil and pseudoisocytosine which had hydrogen bond donor in their minor groove sides. The modified DNAs can be transcribed by T7-RNA polymerase and the transcrption was inhibited by the addition of triplex forming oligonucleotides incorporating artificial bases which can form hydrogen bond with pseudouracil or pseudoisocytosine. We also developed fluorescent DNAs having aromatic groups in their minor groove. The spectroscopic analyses revealed that the fluorescence of the DNAs can be enhanced by addition of triplex forming oligonucleotides.

Research Products

• [Journal Article] Fluorescence enhancement of oligodeoxynucleotides modified with green fluorescent protein chromophore mimics upon triplex formation (2017)
  • Author(s): Kanamori T, Takamura A, Tago N, Masaki Y, Ohkubo A, Sekine M, Seio K.
  • Journal Title: Organic and Biomolecular Chemistry Volume: 15 Issue: 5 Pages: 1190-1197
  • DOI: 10.1039/c6ob01278g
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Enzymatic synthesis and reverse transcription of RNAs incorporating 2 -O-carbamoyl uridine triphosphate (2016)
  • Author(s): Masaki Y, Ito H, Oda Y, Yamazaki K, Tago N, Ohno K, Ishii N, Tsunoda H, Kanamori T, Ohkubo A, Sekine M, Seio K.
  • Journal Title: Chemical Communications Volume: 52 Issue: 87 Pages: 12889-12892
  • DOI: 10.1039/c6cc05796a
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 7-(Benzofuran-2-yl)-7-deazadeoxyguanosine as a fluorescence turn-ON probe for single-strand DNA binding protein (2016)
  • Author(s): Munefumi Tokugawa, Yoshiaki Masaki, Jan Christian Canggadibrata, Kazuhei Kaneko, Takashi Shiozawa, Takashi Kanamori, Morten Grøtli, L. Marcus Wilhelmsson, Mitsuo Sekine and Kohji Seio
  • Journal Title: Chemical Communications Volume: 52 Issue: 19 Pages: 3809-3812
  • DOI: 10.1039/c5cc09700b
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Photo-controlled binding of MutS to photo-caged DNA duplexes incorporating 4-O-(2-nitrobenzyl) or 4-O-[2-(2-nitrophenyl)propyl] thymidine (2016)
  • Author(s): Seio K, Ohno Y, Ohno K, Takeshita L, Kanamori T, Masaki Y, Sekine M.
  • Journal Title: Bioorganic and Medicinal Chemistry Letters Volume: 26 Issue: 19 Pages: 4861-4863
  • DOI: 10.1016/j.bmcl.2016.07.075
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis of 5-[3-(2-aminopyrimidin-4-yl)aminopropyn-1-yl]uracil derivative that recognizes Ade-Thy base pairs in double-stranded DNA (2016)
  • Author(s): Yu Ito, Yoshiaki Masaki, Takashi Kanamori, Akihiro Ohkubo, Kohji Seio, Mitsuo Sekine,
  • Journal Title: Bioorganic and Medicinal Chemistry Letters Volume: 26 Issue: 1 Pages: 194-196
  • DOI: 10.1016/j.bmcl.2015.11.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Synthesis of peptide nucleic acids containing pyridazine derivatives as cytosine and thymine analogs, and their duplexes with complementary oligodeoxynucleotides (2015)
  • Author(s): Takahito Tomori, Yuya Miyatake, Yuta Sato, Takashi Kanamori, Yoshiaki Masaki, Akihiro Ohkubo, Mitsuo Sekine, Kohji Seio
  • Journal Title: Organic Letters Volume: 17 Issue: 6 Pages: 1609-1612
  • DOI: 10.1021/acs.orglett.5b00522
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] スルホンアミド結合で連結された人工核酸の新規合成法 (2017)
  • Author(s): 関谷彰太・北川 諒・田胡信広・正木慶昭・清尾康志
  • Organizer: 第97日本化学会春季年会
  • Place of Presentation: 慶応大学日吉キャンパス
• [Presentation] スルホニル基のα炭素をフッ素置換した 2’,5’-ジデオキシ-5’-ス ルホメチルヌクレオシドの合成 (2017)
  • Author(s): 北川 諒・田胡 信広・関谷彰太・正木慶昭・関根光雄・清尾康志
  • Organizer: 第97日本化学会春季年会
  • Place of Presentation: 慶応大学日吉キャンパス
• [Presentation] ピリダジン-3-オンを核酸塩基部に有する核酸の核酸合成酵素に よる合成 (2017)
  • Author(s): 長岡健斗・友利貴人・竹下玲央・宮 武佑弥・正木慶昭・関根光雄・清尾康志
  • Organizer: 第97日本化学会春季年会
  • Place of Presentation: 慶応大学日吉キャンパス
• [Presentation] DNA ポリメラーゼによる取り込み能向上を目指した光ケージ ドヌクレオシド三リン酸の合成と性質 (2017)
  • Author(s): 竹下玲央・大野健太郎・長岡健斗・正木慶昭・清尾康志
  • Organizer: 第97日本化学会春季年会
  • Place of Presentation: 慶応大学日吉キャンパス
• [Presentation] ピリダジン-3-オンを核酸塩基部に有するC-ヌクレオシドの合 成と性質 (2016)
  • Author(s): 友利貴人 長岡健斗 宮武佑弥 正木慶昭 関根光雄 清尾康志
  • Organizer: 日本化学会第９６春季年会
  • Place of Presentation: 同志社大学京田辺キャンパス
  • Year and Date: 2016-03-27
• [Presentation] 塩基部 5 位に 3-メチルベンゾフラン誘導体を導入した 2´-デオ キシウリジンの合成と蛍光特性 (2016)
  • Author(s): 宮村大地 金森功吏 正木慶昭 関根光雄 清尾康志
  • Organizer: 日本化学会第９６春季年会
  • Place of Presentation: 同志社大学京田辺キャンパス
  • Year and Date: 2016-03-24
• [Presentation] Deformability analysis of chemically modifi ed RNA and its applicability for estimation of RNA duplex stability (2016)
  • Author(s): Masaki Y, Miyasaka R, Yamamoto K, Yoshida K, Ohkubo A, Sekine M, Seio K.
  • Organizer: The 43rd International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: Kumamoto University
  • Int'l Joint Research
• [Presentation] Chemical and enzymatic synthesis of photo-caged DNA containing of N1 -nitrobenzyl-2'- deoxypseudouridine for UV dependent regulation of transcription (2016)
  • Author(s): Takeshita L, Ohno K, Masaki Y, Sekine M, Seio K.
  • Organizer: The 43rd International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: Kumamoto University
  • Int'l Joint Research
• [Presentation] Synthesis and Enzymatic properties of C-nucleoside Triphosphate Containing Pyridazin-3- one as a uracil analog (2016)
  • Author(s): Tomori T, Nagaoka K, Miyatake Y, Masaki Y, Sekine M, Seio K.
  • Organizer: The 43rd International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: Kumamoto University
  • Int'l Joint Research
• [Presentation] Base Pair Recognition of Alpha-deoxyribonucleosides with Unmodified Nucleobase and 8-Oxo-adenine in Antiparallel DNA Triplex (2016)
  • Author(s): Inde T, Masaki Y, Sekine M, Seio K.
  • Organizer: The 43rd International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: Kumamoto University
  • Int'l Joint Research
• [Presentation] ASOのコントロールリリースを指向したシス-1,2-ジオールの非対称ジ炭酸エステルリンカーの合成 (2016)
  • Author(s): 岸村智太・正木慶昭・清尾康志
  • Organizer: 日本核酸医薬学会第２回年会
  • Place of Presentation: 東京理科大学葛飾キャンパス
• [Presentation] 2´位に種々のカルバモイルエチル型修飾を有するオリゴヌクレオチドの合成と性質 (2016)
  • Author(s): 吉田圭汰・正木慶昭・山本恵士・入山友輔 ・中嶋宏之・金木達朗 ・関根光雄 ・清尾康志
  • Organizer: 日本核酸医薬学会第２回年会
  • Place of Presentation: 東京理科大学葛飾キャンパス
• [Presentation] Synthesis of deoxyuridine derivatives modified with 2,4-diaminopyrimidine moiety for the development of high affinity triplex forming oligonucleotides (2015)
  • Author(s): Yu Ito, Takashi Kanamori, Yoshiaki Masaki, Akihiro Ohkubo, Kohji Seio, Mitsuo Sekine
  • Organizer: The 42th International symposium on nucleic acids chemistry
  • Place of Presentation: I-messae hall, Himeji
  • Year and Date: 2015-09-23
  • Int'l Joint Research
• [Presentation] Synthesis of oligodeoxynucleotides containing 2’-deoxy-pseudoisocytidine for the development of chemically modified DNA duplexes and triplexes (2015)
  • Author(s): Ayano Yamazaki, Kei Yamaguchi, Takashi Kanamori, Yoshiaki Masaki, Mitsuo Sekine, Kohji Seio
  • Organizer: The 42th International symposium on nucleic acids chemistry
  • Place of Presentation: I-messae hall, Himeji
  • Year and Date: 2015-09-23
  • Int'l Joint Research
• [Presentation] ピリダジン骨格を核酸塩基部に有する新規ペプチド核酸の合成および性質 (2014)
  • Author(s): 友利貴人 宮武佑弥 金森功吏 正木慶昭 大窪章寛 関根光雄 清尾康志
  • Organizer: 第44回 複素環化学討論会
  • Place of Presentation: 札幌市民ホール
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] (8)Synthesis and hybridization properties of peptide nucleic acids containing aminopyridazine derivatives as cytosine surrogates (2014)
  • Author(s): Takahito Tomori, Yuya Miyatake, Yuta Satou, Takashi Kanamori, Yoshiaki Masaki, Akihiro Ohkubo, Mitsuo Sekine, Kohji Seio
  • Organizer: XXI Round Table on Nucleosides, Nucleotides and Nucleic Acids: Chemical Biology of Nucleic Acids,
  • Place of Presentation: Poznan Poland
  • Year and Date: 2014-08-24 – 2014-08-28