血栓形成の制御を目指した多数のジスルフィド結合を持つ天然物様環状ペプチドの開発

2021 Fiscal Year Annual Research Report

• Project/Area Number: 20J11284
• Research Institution: The University of Tokyo
• Principal Investigator: LIU Wenyu 東京大学, 理学系研究科, 特別研究員(DC2)
• Project Period (FY): 2020-04-24 – 2022-03-31
• Keywords: disulfide-rich peptide / in vitro selection / peptide discovery

Outline of Annual Research Achievements

This research aims at discovery of de novo disulfide-rich peptides (DRPs) with desired conformations and biological activities using in vitro selection. In this year of my JSPS fellowship, I first finished the paper publication of the research that identified an ultrapotent cyclotide-based FXIIa inhibitor. This work was published on J. Am. Chem. Soc. 2021, 143, 18481-18489. In this year, I also continued the research of controlling disulfide connectivity in DRPs taking advantage of protected cysteines. In brief, I constructed bicyclic or tricyclic DRP libraries with controllable disulfide conformations and conducted in vitro selection to yield several potent target-binding peptides with designed structures. The following work is being performed and will be summarized into publications.

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] An Ultrapotent and Selective Cyclic Peptide Inhibitor of Human β-Factor XIIa in a Cyclotide Scaffold (2021)
  • Author(s): Wenyu Liu, Simon J. de Veer, Yen-Hua Huang, Toru Sengoku, Chikako Okada, Kazuhiro Ogata, Christina N. Zdenek, Bryan G. Fry, Joakim E. Swedberg, Toby Passioura, David J. Craik, and Hiroaki Suga
  • Journal Title: J. Am. Chem. Soc. Volume: 143 Pages: 18481-18489
  • DOI: 10.1021/jacs.1c07574
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Potent Cyclic Peptide Inhibitors of FXIIa Discovered by mRNA Display with Genetic Code Reprogramming (2021)
  • Author(s): Daniel J. Ford, Nisharnthi M. Duggan, Sarah E. Fry, Jorge Ripoll-Rozada, Stijn M. Agten, Wenyu Liu, et al.
  • Journal Title: J. Med. Chem. Volume: 64 Pages: 7853-7876
  • DOI: 10.1021/acs.jmedchem.1c00651
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Discovery of a cyclotide-based coagulation Factor XIIa inhibitor by mRNA display (2021)
  • Author(s): Wenyu Liu
  • Organizer: The 101st CSJ Annual Meeting
• [Presentation] Development of an ultrapotent and selective human β-factor XIIa inhibitor in a cyclotide scaffold (2021)
  • Author(s): Wenyu Liu
  • Organizer: The 58th Japanese Peptide Symposium
• [Presentation] Development of a cyclotide-based ultrapotent, selective coagulation Factor XIIa inhibitor using mRNA display (2021)
  • Author(s): Wenyu Liu
  • Organizer: Pacifichem 2021
  • Int'l Joint Research