2017 Fiscal Year Annual Research Report
| Project/Area Number |
16F16033
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
菅 裕明 東京大学, 大学院理学系研究科(理学部), 教授 (00361668)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MAINI RUMIT 東京大学, 大学院理学系研究科, 外国人特別研究員
|
|---|
| Project Period (FY) |
2016-04-22 – 2018-03-31
|
| Keywords | mRNA / translation / thioamide |
|---|
| Outline of Annual Research Achievements |
The synthesis of proposed unnatural amino acid derivatives were attempted but failed. Therefore, focus was diverted towards the synthesis of peptides containing a backbone thioamide moiety.
Ribosome-mediated thioamide bond catalysis was demonstrated four decades ago, however, the product was merely a thioamide-dipetide, which was formed in the absence of any mRNA. Since then, there has been no report on the ribosomal synthesis of peptides containing thioamide bonds. Here, we successfully demonstrated that the ribosome is capable in catalyzing the formation of a thioamide bond in an mRNA dependent fashion during peptide translation. Central to this achievement was the flexizyme technology that, for the very first time, allowed for the preparation of an amino(thio)acyl-tRNA, AlaS-tRNAGluE2. By reprogramming the genetic code in the FIT system, we synthesized peptide with a thioamide backbone. The chemical synthesis of peptides with one or more thioamide backbones has already been established; and the strategy presented here can allow for the generation of a ~10^12 membered library of peptides with one or more thioamide backbones via mRNA display platform. Therefore, in the future, a combination of mRNA display and chemical synthesis will lead to the discovery of macrocyclic thioamide-peptides with attractive biological and pharmacological properties.
|
| Research Progress Status |
29年度が最終年度であるため、記入しない。
|
| Strategy for Future Research Activity |
29年度が最終年度であるため、記入しない。
|
