Chemical synthesis of ubiquitin codes

2022 Fiscal Year Final Research Report

• Project Area: New frontier for ubiquitin biology driven by chemo-technologies
• Project/Area Number: 18H05504
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: The University of Tokyo
• Principal Investigator: Okamoto Akimitsu 東京大学, 大学院工学系研究科(工学部), 教授 (60314233)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Keywords: ユビキチン / 化学合成 / 酵素

Outline of Final Research Achievements

We designed ubiquitin derivatives with a photodegradable protecting group on the lysine residue used for polymerization. Using this ubiquitin derivative, we were able to control the length and branching position of ubiquitin by repeated enzymatic elongation and deprotection of the protecting group by light. Control of branching position was achieved without separation of intermediates, allowing one-pot synthesis of K63 triubiquitin chains and K63/K48 heterotypic tetraubiquitin chains with defined branching positions. This study provides a chemical platform for the efficient construction of long polyubiquitin chains with defined branching structures and will facilitate the elucidation of the essential relationship between function and structure of heterotypic chains that has been overlooked.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

本研究は、光制御による段階的な酵素的集合を確立することで、構造規定されたヘテロ型ポリユビキチン鎖の最初のワンポット合成プラットフォームになる。今回のワンポットでのヘテロ型鎖形成は、分岐トポロジーを定義したヘテロ型ポリユビキチン鎖の前例のない合成プラットフォームであり、ヘテロ型鎖の特徴的な機能をコードするこれまで見過ごされてきた構造決定因子を解決できる可能性を持っている。