Ribosomal synthesis of polyketide-peptide hybrid molecules
Project/Area Number |
17H04762
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Biomolecular chemistry
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Research Institution | The University of Tokyo |
Principal Investigator |
Goto Yuki 東京大学, 大学院理学系研究科(理学部), 准教授 (70570604)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
Fiscal Year 2019: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2018: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2017: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
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Keywords | 翻訳合成 / ポリケチド / ペプチド / 擬天然物 / 生合成 |
Outline of Final Research Achievements |
Many polyketide-peptide hybrid molecules have been isolated as bioactive natural products. In this research, we aimed to establish a new method for ribosomal synthesis of peptides bearing unique polyketide-like moieties. To this end, we tested several different synthetic approaches, and eventually demonstrated that peptides with polyketide-like long backbone structures can be expressed by a combination of in vitro translation and posttranslational acyl transfer reaction. This synthetic method has indeed allowed for in vitro ribosomal synthesis of a model bioactive molecule.
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Academic Significance and Societal Importance of the Research Achievements |
試験管内翻訳合成法は、中分子薬剤候補の化合物ライブラリー構築と探索に近年活発に活用されている。本研究により試験管内翻訳合成で合成できる化合物のバリエーションを拡大させ、実際に生物活性分子を生産できることが実証されたことは、天然物様のポリケチド-ペプチド複合分子を活用した擬天然物創薬戦略の基盤となりえる。
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] Exploring the Post-translational Enzymology of PaaA by mRNA Display2020
Author(s)
Fleming, S. R., Himes, P. M., Ghodge, S. V., Goto, Y., Suga, H., Bowers, A. A.
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Journal Title
J Am Chem Soc
Volume: 142
Issue: 11
Pages: 5024-5028
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Improved Stability of siRNA-Loaded Lipid Nanoparticles Prepared with a PEG-Monoacyl Fatty Acid Facilitates Ligand-Mediated siRNA Delivery2020
Author(s)
Sakurai, Y., Mizumura, W., Ito, K., Iwasaki, K., Katoh, T., Goto, Y., Suga, H., Harashima, H.
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Journal Title
Mol Pharm
Volume: 17
Issue: 4
Pages: 1397-1404
DOI
Related Report
Peer Reviewed
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[Journal Article] Non-competitive cyclic peptides for targeting enzyme?substrate complexes2018
Author(s)
McAllister T. E.、Yeh T.-L.、Abboud M. I.、Leung I. K. H.、Hookway E. S.、King O. N. F.、Bhushan B.、Williams S. T.、Hopkinson R. J.、M?nzel M.、Loik N. D.、Chowdhury R.、Oppermann U.、Claridge T. D. W.、Goto Y.、Suga H.、Schofield C. J.、Kawamura A.
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Journal Title
Chemical Science
Volume: 9
Issue: 20
Pages: 4569-4578
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Highly selective inhibition of histone demethylases by de novo macrocyclic peptides.2017
Author(s)
Kawamura A, Mnzel M, Kojima T, Yapp C, Bhushan B, Goto Y, Tumber A, Katoh T, King ON, Passioura T, Walport LJ, Hatch SB, Madden S, Muller S, Brennan PE, Chowdhury R, Hopkinson RJ, Suga H, Schofield CJ.
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Journal Title
Nat Commun
Volume: 8
Issue: 1
Pages: 14773-14773
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Conformational and chemical selection by a trans-acting editing domain.2017
Author(s)
Danhart EM, Bakhtina M, Cantara WA, Kuzmishin AB, Ma X, Sanford BL, Vargas-Rodriguez O, Ko; M, Goto Y, Suga H, Nakanishi K, Micura R, Foster MP, Musier-Forsyth K.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 114
Issue: 33
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Efficient siRNA Delivery by Lipid Nanoparticles Modified with a Nonstandard Macrocyclic Peptide for EpCAM-Targeting.2017
Author(s)
Sakurai Y, Mizumura W, Murata M, Hada T, Yamamoto S, Ito K, Iwasaki K, Katoh T, Goto Y, Takagi A, Kohara M, Suga H, Harashima H.
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Journal Title
Mol Pharm
Volume: 14
Issue: 10
Pages: 3290-3298
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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