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

开发具有多个二硫键的类天然产物环肽，旨在控制血栓形成

• 批准号: 20J11284
• 负责人: LIU Wenyu
• 金额: $ 1.09万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-24 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20J11284/
• 关键词: disulfide-rich peptide; in vitro selection; peptide discovery; disulfide-rich peptides

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.

本研究的目的是通过体外筛选的方法来发现具有所需构象和生物活性的富含二硫键的多肽。在我的JSPS奖学金的这一年，我第一次完成了论文发表的研究，确定了一个超有效的环肽基FXIIa抑制剂。这项工作发表在J. Am。2021，143，18481-18489中所述。在这一年里，我还继续研究利用受保护的半胱氨酸控制DRPs中的二硫键连接。简而言之，我构建了具有可控二硫键构象的双环或三环DRP文库，并进行了体外选择，以产生具有设计结构的几种有效的靶点结合肽。正在开展以下工作，并将在出版物中进行总结。

项目成果

Development of a cyclotide-based ultrapotent, selective coagulation Factor XIIa inhibitor using mRNA display

使用 mRNA 展示开发基于环肽的超强选择性凝血因子 XIIa 抑制剂

• 发表时间: 2021
• 作者: Yamamoto Tsuyoshi;Kato Takeo;石井雅巳;Wenyu Liu
• 通讯作者: Wenyu Liu

An Ultrapotent and Selective Cyclic Peptide Inhibitor of Human β-Factor XIIa in a Cyclotide Scaffold

• DOI: 10.1021/jacs.1c07574
• 发表时间: 2021-11-01
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Liu, Wenyu;de Veer, Simon J.;Suga, Hiroaki
• 通讯作者: Suga, Hiroaki

Development of an ultrapotent and selective human β-factor XIIa inhibitor in a cyclotide scaffold

在环肽支架中开发超强选择性人 β 因子 XIIa 抑制剂

• 发表时间: 2021
• 作者: 石井雅巳;Wenyu Liu
• 通讯作者: Wenyu Liu

Discovery of a cyclotide-based coagulation Factor XIIa inhibitor by mRNA display

通过 mRNA 展示发现基于环肽的凝血因子 XIIa 抑制剂

• 发表时间: 2021
• 作者: Wenyu Liu

Potent Cyclic Peptide Inhibitors of FXIIa Discovered by mRNA Display with Genetic Code Reprogramming

• DOI: 10.1021/acs.jmedchem.1c00651
• 发表时间: 2021-05-28
• 期刊: JOURNAL OF MEDICINAL CHEMISTRY
• 影响因子: 7.3
• 作者: Ford, Daniel J.;Duggan, Nisharnthi M.;Payne, Richard J.
• 通讯作者: Payne, Richard J.