Synthetic post-translational modifications

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19197
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry and related fields
• Research Institution: Kyoto University
• Principal Investigator: Uesugi Motonari 京都大学, 化学研究所, 教授 (10402926)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: ケミカルバイオロジー / 化合物ライブラリー

Outline of Final Research Achievements

Small-molecule probes that are covalently attached to a protein of interest often serve as tools for biological research by facilitating detection and purification of the protein and its binding partners. This project proposes a new approach to discovering covalent chemical probes that label specific proteins. To identify such probe-protein pairs in an unbiased way, we have been taking advantage of our in-house chemical library that consists of 1,657 electrophile synthetic compounds and 83 reactive natural products. The screening of the library isolated three promising molecules: two synthetic molecules and one natural product. We are currently in the process of analyzing their effects on the biological functions of the target proteins.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

多数のタンパク質に対して多数の化合物をスクリーニングし、「人工翻訳後修飾」を探索した例はこれまでになく、世界初。利用する反応性化合物ライブラリーは世界的に独自性が高い。成功すれば、これまでになかった新しい知識を生み出して、生理活性小分子化合物や創薬の研究方向を変革する潜在的可能性がある。