Deformability analysis for rational design of sugar-modified oligonucleotides
| Project/Area Number |
26810086
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Bio-related chemistry
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| 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)
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| 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 |
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| 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.
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Report
(4 results)
Research Products
(14 results)
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[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.
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Journal Title
Chemical Communications
Volume: 52
Issue: 87
Pages: 12889-12892
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[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
Int'l Joint Research
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[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
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