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Deformability analysis for rational design of sugar-modified oligonucleotides

Research Project

Project/Area Number 26810086
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bio-related chemistry
Research InstitutionTokyo Institute of Technology

Principal Investigator

Masaki Yoshiaki  東京工業大学, 生命理工学院, 助教 (00578544)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords核酸医薬 / 化学修飾核酸 / RNA / 分子動力学計算 / 二重鎖融解温度 / 修飾核酸 / アンチセンス核酸 / 分子設計
Outline of Final Research Achievements

Nucleic acid drug is a promising candidate for the development of effective treatment for genetic diseases. However, nucleic acid drugs have multiple issues and therefore have not been widely used. In this study, we focused on the affinity of nucleic acid drug with the target transcripts. We used molecular dynamic simulations for the development of rational molecular design method. The effect of chemical modification on duplex stability could be evaluated by calculating the force constants of the fluctuation of base pair step parameters during molecular dynamic simulations. In addition, we revealed that the influence on the fluctuation of phosphate backbone plays a key role on duplex stability. In summary, we developed a new molecular design method to solve the affinity issue of nucleic acid drugs.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (14 results)

All 2017 2016 2015 2014

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 4 results,  Open Access: 2 results) Presentation (8 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] Deformability Calculation for Estimation of the Relative Stability of Chemically Modified RNA Duplexes.2017

    • Author(s)
      Masaki Y, Sekine M, Seio K.
    • Journal Title

      Current Protocols in Nucleic Acid Chemistry

      Volume: 68 Issue: 1

    • DOI

      10.1002/cpnc.25

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Enzymatic synthesis and reverse transcription of RNAs incorporating 2 -O-carbamoyl uridine triphosphate2016

    • 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

    • Related Report
      2016 Annual Research Report
    • 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 protein2016

    • 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

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A New Microfluidic Phase-Transfer Reaction Using HPLC Guard Columns as the Reactor for the N3-Protection of Uridine Derivatives2015

    • Author(s)
      Nobuhiro Tago, Yoshiaki Masaki, Hiroshi Nagasawa, Takashi Kanamori, Akihiro Ohkubo, Kohji Seio, Mitsuo Sekine
    • Journal Title

      Synlett

      Volume: 26 Issue: 18 Pages: 2578-2582

    • DOI

      10.1055/s-0035-1560264

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthesis and properties of oligonucleotides modified with 2'-O-(2-carboxyethyl)nucleotides and their carbamoyl derivatives.2014

    • Author(s)
      Yamada T, Masaki Y, Okaniwa N, Kanamori T, Ohkubo A, Tsunoda H, Seio K, Sekine M
    • Journal Title

      Org Biomol Chem.

      Volume: 12 Issue: 33 Pages: 6457-6464

    • DOI

      10.1039/c4ob01260g

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Deformability analysis of chemically modified RNA and its applicability for estimation of RNA duplex stability2016

    • Author(s)
      Yoshiaki Masaki, Ryuta Miyasaka, Keishi Yamamoto, Keita Yoshida, Akihiro Ohkubo, Mitsuo Sekine, Kohji Seio.
    • Organizer
      The 43rd International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      熊本大学
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 糖部化学修飾RNA二重鎖の変形能と二重鎖融解温度の関係2016

    • Author(s)
      正木 慶昭, 吉田 圭汰, 山本 恵士, 関根 光雄, 清尾 康志
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Place of Presentation
      石川県立音楽堂
    • Year and Date
      2016-09-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 2-(N-エチルカルバモイル)エチル構造を糖部に有する修飾核酸の合成と性質2016

    • Author(s)
      山本 恵士・正木 慶昭・吉田 圭太・入山 友輔・中嶋 宏之・金木 達朗・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
    • Related Report
      2015 Research-status Report
  • [Presentation] Enhancement of exon skipping efficiency by using antisense oligonucleotides containing 2-thiothymidine derivatives2015

    • Author(s)
      Masaki, Y.; Yamamoto, K.; Inde, T; Nagata, T.; Tanihata, J.; Iriyama, Y.; Takeda, S.; Sekine, M.; Seio, K.
    • Organizer
      日本核酸医薬学会 第一回年会
    • Place of Presentation
      京都テルサ
    • Year and Date
      2015-11-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Enhancement of exon skipping by 2´-O-(N-methylcarbamoyl)ethyl (MCE) and/or nucleobase modified nucleosides incorporation into phosphorothioate oligonucleotides2015

    • Author(s)
      Masaki, Y.; Yamamoto, K.; Inde, T; Nagata, T.; Tanihata, J.; Iriyama, Y.; Takeda, S.; Seio, K.; Sekine, M.
    • Organizer
      11th of Annual Meeting of the Oligonucleotide Therapeutics Society
    • Place of Presentation
      Leiden, the Netherlands
    • Year and Date
      2015-10-11
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Synthesis and properties of oligonucleotide containing 2´-O-[2-(N-methylcarbamoyl)ethyl] modified 2-thioribothymidine2015

    • Author(s)
      Yamamoto, K.,; Masaki, Y,; Ishii, A,; Inde, T,; Tanibata, J,; Nagata, T,; Kanamori, T,; Takeda, S,; Sekine, M,; Seio , K.
    • Organizer
      第17回日本RNA学会年会
    • Place of Presentation
      ホテルライフォート札幌
    • Year and Date
      2015-07-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Effective N-benzoylation of uridine derivatives using a two-phase microfluidic system2014

    • Author(s)
      Tago N.; Masaki Y.; Ohkubo A.; Nagasawa H.; Kanamori T.; Seio K.; Sekine M.
    • Organizer
      The 41st International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      福岡(日本)
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Synthesis of 2´-O-carbamoyl uridine triphosphate and its applicability to aptamer selection2014

    • Author(s)
      Masaki, Y.; Ito, H.; Yamazaki, K.; Tsunoda, H.; Kanamori, T.; Ohkubo, A.; Seio, K.; Sekine, M.
    • 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
    • Related Report
      2014 Research-status Report
  • [Book] Chemical Biology of Nucleic Acids, fundamentals and clinical applications2014

    • Author(s)
      Masaki, Y.; Yamada, T.; Saneyoshi, H.; Ohkubo, A.; Seio, K.; Sekine, M.
    • Total Pages
      599
    • Publisher
      Springer
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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