Development of four-base codon decoding system and its application to highly diversified peptide drug discovery

Research Project

Project/Area Number	18H02083
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 37010:Bio-related chemistry
Research Institution	Japan Advanced Institute of Science and Technology
Principal Investigator	Hohsaka Takahiro 北陸先端科学技術大学院大学, 先端科学技術研究科, 教授 (30263619)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000) Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000) Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000) Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords	非天然アミノ酸 / 遺伝暗号 / ４塩基コドン / ペプチド / 無細胞翻訳系 / 遺伝暗号拡張 / 非天然ペプチド / 無細胞翻訳 / 分子進化
Outline of Final Research Achievements	In this study, in order to make it possible to introduce a wide variety of nonnatural amino acids into peptides and proteins, we developed four-base codon decoding system in which the genetic code originally consisted of 3 letters is expanded to 4 letters. As a result, we found that a large number of four-base codons can be used for the introduction of nonnatural amino acids, and established a method for collectively evaluating the translation efficiency of four-base codons.
Academic Significance and Societal Importance of the Research Achievements	本研究成果は、生物の基本原理である遺伝暗号が大幅に拡張できることを明らかにしたとともに、多種多様な非天然アミノ酸からなるペプチドやタンパク質の生合成を可能にするものである。本手法は、ペプチド創薬技術と組み合わせることで、多様な非天然アミノ酸からなるペプチドの中から特定の標的分子に結合するペプチドを取得することを可能にし、新たなペプチド医薬の取得などへの応用が期待される。