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2019 Fiscal Year Final Research Report

Histone-Selective Synthetic Acylation Mediated by Chemical Catalyst as Potential anti-Cancer Strategy

Research Project

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Project/Area Number 17K19479
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Pharmaceutical Sciences and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Kanai Motomu  東京大学, 大学院薬学系研究科(薬学部), 教授 (20243264)

Project Period (FY) 2017-06-30 – 2020-03-31
Keywords触媒 / エピゲノム / タンパク質翻訳後修飾 / ヒストンアシル化 / 遺伝子転写
Outline of Final Research Achievements

Life emerges from a network of biomolecules and chemical reactions. Enzymes intervene in the chemical reactions in the living system, and the abnormal function of the enzymes or the abnormal chemical reactions in the living system is closely related to the loss of the homeostasis of the life and the diseases. The purpose of this study is to focus on lysine acetylation of histone proteins, which is a post-translational modification that positively regulates gene transcription, and to introduce histone acetylation in an enzyme-independent manner by artificial chemical catalysis in vivo. In the present study, we found that the chemical catalyst DSH selectively promoted acetylation of endogenous proteins at specific residues, including histones, in living cells. Furthermore, we have developed a chemical catalyst, HXA, which is more active than DSH.

Free Research Field

触媒

Academic Significance and Societal Importance of the Research Achievements

生命現象は有機分子と化学反応のネットワークから発現し、そのネットワーク異常が病態を引き起こす。生体内の化学反応は通常、酵素により促進されるが、酵素の機能を代替する化学触媒をつくることを目的として研究をおこなっている、本研究では、遺伝子転写を正に制御するヒストンタンパク質のリジンアシル化を促進する化学触媒を開発した。これにより、エピゲノムを化学的に制御することによる病態治療の端緒を拓いた。

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Published: 2021-02-19  

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