Exploration of synthetic molecules that control intrinsically disordered proteins

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K13098
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Shinshu University
• Principal Investigator: Ohkanda Junko 信州大学, 学術研究院農学系, 教授 (50233052)
• Co-Investigator(Renkei-kenkyūsha): IMANISHI Miki 京都大学, 化学研究所, 講師 (80362391)
• Research Collaborator: HOSOYA Yusuke
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 非構造性たんぱく質 / 概日時計転写因子 / IDPs / 阻害剤探索 / Bmal1 / Clock

Outline of Final Research Achievements

Synthetic compounds that control the structural changes and interactions of intrinsically disordered proteins (IDPs) are expected to be a breakthrough that paves the way for new drug discovery. However, details of IDPs are still unknown, and almost no inhibitors that specifically disrupt IDP’s functions have been found. In this study, we focused on the Circadian Clock transcription factors Clock and Bmal 1 that are known as typical IDPs in which more than 30% in length are highly disordered. We obtained truncated version of recombinant Clock and Bmal1, and constructed a system of fluorescent polarization assay for heterodimer formation of Clock/Bmal 1. As a result of evaluation of low-molecular-weight aromatic compound library, we succeeded in finding a compound which significantly inhibits intermolecular interaction of Clock / Bmal1.

Free Research Field

生物有機化学