| Project/Area Number |
15H06446
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Drug development chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TARASHIMA Noriko 徳島大学, 大学院医歯薬学研究部(薬学系), 助教 (90755183)
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| Project Period (FY) |
2015-08-28 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | siRNA / RNA干渉 / ケミカルプローブ / 自然免疫応答 / 核酸創薬 / 核酸医薬 |
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| Outline of Final Research Achievements |
In this study, we have developed the logical chemical probes comprising 7-bromo-7-deazaadenosine (Br7C7A) and 3-bromo-3-deazaadenosine (Br3C3A) in order to investigate siRNA-RNAi related protein interactions. In a helical structure of nucleic acids, two grooves exist; a major and a minor. In molecular recognition, proteins are thought to recognize nucleic acids by the shape of their groove(s). The bromo substituents of Br7C7A and Br3C3A are expected to locate in the major and the minor grooves, respectively, and to act as a steric hindrance in each groove when these chemical probes are incorporated into siRNAs. A comprehensive investigation using siRNAs containing these chemical probes revealed that (i) incorporation of Br3C3A(s) at the 5’-end of the passenger strand obviously enhanced their RNAi activity, and (ii) direction of RISC assembly is determined by the interaction between Ago2 and siRNA in the minor groove near the 5’-end of the passenger strand.
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