2007 Fiscal Year Final Research Report Summary
Development of chemical tools for nucleic acide-proteim interactions and its utility for siRNA medicine
| Project/Area Number |
18510180
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Living organism molecular science
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| Research Institution | Hokkaido University |
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Principal Investigator |
MINAKAWA Noriaki Hokkaido University, Grad. School of Pharm. Sci, Associate Professor (40209820)
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| Project Period (FY) |
2006 – 2007
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| Keywords | nucleic acids-protein interaction / RNA interference / RNA / 3-bromo-3-deazaadenosine / 7-bromo-7-deazaadensine |
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| Research Abstract |
The aim of this work is to develop chemical tools for nucleic acids-protein interactions and its utility for siRNA medicine. We designed a pair of chemical probes to investigate DNA-protein interactions specifically the incorporation of 7-bromo-7-deazaadenine and 3-bromo-3-deazaadenine 2'-deoxynucleosides (Br^7C^7dA and Br^3C^3dA) into oligodeoxynucleotides (ODNs) and their utility. Whereas the bromo substituent of the Br^7C^7dA unit in an ODN duplex acts sterically to inhibit binding with NF-kB, which interacts with the duplex in its major groove, the bromo substituent of the Br^7C^7dA unit acts sterically to inhibit binding with Rnase H, which interacts with the duplex in its minor groove. In addition, the utilization of ODNs containing 7-deazaadenine and 3-deazaadenine 2'-deoxynucleosides (C^7dA and C^3dA), together with the pair of chemical probes, afforded valuable information on the requirement of nitrogen atoms located in either the major or minor grooves. Accordingly, we were able to show the utility of ODNs containing Br^7C^7dA, Br^3C^3dA, C^7dA, and C^3dA for the investigation of DNA-protein interactions. Development this chemical tool for siRNA medicine is under investigation.
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