Development of prenylated peptides interacting with intracellular targets

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H02866
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: Kyoto University (2023); The University of Tokyo
• Principal Investigator: Goto Yuki 京都大学, 理学研究科, 教授 (70570604)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 中分子ペプチド / プレニル化ペプチド / 擬天然物 / 生物活性分子

Outline of Final Research Achievements

The aim of this project was to establish a system for the development of artificial prenylated peptides with desired binding ability by utilizing prenyl modifications found in natural product peptides. Specifically, more than 25 putative peptide prenyltransferases have been identified, and among these, we succeeded in discovering and identifying five new groups of prenyltransferases that perform unprecedented modes of prenylation (Goal A), and in constructing more diverse artificial prenylated residues through prenylation of artificial amino acid derivatives (Goal B). Furthermore, we established an in vitro selection system for artificial PMPs ligands using these prenylating enzymes (Goal C) and succeeded in developing artificial prenylated peptide agents that inhibit specific target proteins and can internalize into cells (Goal D).

Free Research Field

生体関連化学

Academic Significance and Societal Importance of the Research Achievements

次世代型の創薬候補分子として、中分子サイズの環状ペプチドが近年注目されている。しかしながら、親水性の高いアミド結合を主鎖にもつペプチドは、一般的 に細胞膜を通過できないため、細胞内移行配列に頼らずに細胞内標的を阻害する人工ペプチド薬剤の開発原理は、残念ながら現時点では存在しない。本研究成果は、細胞内標的を阻害する人工ペプチド薬剤開発の基盤技術となりうる。