2014 Fiscal Year Annual Research Report
| Project/Area Number |
13F03766
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| Research Institution | The University of Tokyo |
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Principal Investigator |
菅 裕明 東京大学, 理学(系)研究科(研究院), 教授 (00361668)
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| Co-Investigator(Kenkyū-buntansha) |
ROGERS Joseph 東京大学, 理学(系)研究科(研究院), 外国人特別研究員
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 遺伝暗号 / 特殊ペプチド / チオオキシカルボン酸 / tRNAアルシ化 / 翻訳 |
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| Outline of Annual Research Achievements |
I have started two main projects. With Dr Shoji, Kobe University, I have used the RaPID system to find cyclic peptide inhibitors for the protein USP15. I carried out two selections, the first using reprogramming of initiation only and the second included 4 N-methylated amino acids. There were some obstacles with regard to protein stability and significant deviations from the published protocol (Yamagishi 2011) were required. Cyclic peptides have been synthesized, purified and sent to Dr. Shoji for in vivo analysis.
The second project is with the Huc group in Bordeaux, France. They have pioneered the design and synthesis of oligoamide, aromatic ‘foldamers’. A project has been agreed upon to use the Suga techniques to develop a peptide-based bimolecular interface with these unnatural foldamers. I have selected peptides to bind these foldamers and shown the ability of foldamer monomers to initiate translation of peptides.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Overall the scientific progress has been good. The first project was chosen to learn the methods of the Suga lab. Even though USP15 was a new target, and the genetic code had to be heavily reprogrammed, the selections were successful. With good in vivo results, this will yield a publication and, potentially, an anti-viral strategy.
The work on the second, foldamer project has been very successful so far, and has the potential to yield high-impact publishable results. A selection against a non-biological target has not been tried before and my work has demonstrated, for the first time, that this is possible. The incorporation of foldamer units into peptides is also showing promise.
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| Strategy for Future Research Activity |
Upon receipt of good in vivo data, the binding of selected peptides to USP15 will be tested using SPR. The combined data should be sufficient for publication.
First, peptides discovered during the foldamer selection will be synthesized and purified. Their binding to the foldamer will be quantified using SPR, CD or ITC. Second, another selection is planned to find peptides that bind an alternative foldamer. Finally, a number of monomers and smaller oligomers of foldamer units are being synthesized by the collaborators and will be tested for incorporation into peptides using the Suga methods.
A review for Organic and Biomolecular chemistry has been written, this is to be published.
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