2018 Fiscal Year Annual Research Report
ペプチドセレクションによる酵素ミミック創薬のための戦略
| Project/Area Number |
18F18727
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| Research Institution | The University of Tokyo |
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Principal Investigator |
菅 裕明 東京大学, 大学院理学系研究科(理学部), 教授 (00361668)
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| Co-Investigator(Kenkyū-buntansha) |
TSIAMANTAS CHRISTOS 東京大学, 大学院理学系研究科, 外国人特別研究員
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| Project Period (FY) |
2018-07-25 – 2019-03-31
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| Keywords | FIT system / Foldamers / Macrocyclic peptides |
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| Outline of Annual Research Achievements |
This work has harvested the potential of flexizymes (artificial aminoacylation ribozymes) coupled to an in vitro translation system (the “flexible” in vitro translation system, FIT), led to the ribosomal incorporation of the largest and bulkiest residues to date. Briefly, foldamers -molecules with a strong tendency to adopt a folded conformation- composed of aromatic oligoamides have been recently proven capable of initiating translation, yielding the first-of-their-kind foldamer-peptide-hybrids. In our current work, we expanded the repertoire of foldamer functionalities and have demonstrated that side-chain modification of the helical structures grants access to previously inaccessible chemical and structural space. The incorporation of both the bulkiest and largest single residues that have been introduced by the ribosome has been demonstrated. Additionally, intrigued by the ribosomal tolerance towards aromatic oligoamides during translation initiation, we advanced our investigations and explored the possibility of incorporating these abiotic molecules as appendages during translation elongation. Our results indicated that the incorporation of an amino acid residue with a foldamer on the side-chain, as long as a heptapeptide, is feasible. It demonstrates for the first time the tolerance of the ribosome towards residues of that size and expands the current understanding on the limitations of the translational machinery. The above studies have paved the way towards the introduction of foldamers into mRNA display for the discovery of functional foldamer-peptide hybrids.
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| Research Progress Status |
平成30年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
平成30年度が最終年度であるため、記入しない。
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Research Products
(6 results)
