ボロナート補助ヒドロキサム酸触媒による生細胞タンパク質の修正
Christopher Adamson1, Hidetoshi Kajino1, Shigehiro A Kawashima1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-0033.
Journal of the American Chemical Society
|September 10, 2021
まとめ
新しいボロナート補助ヒドロキサミ酸 (BAHA) 触媒は,生体細胞における選択的タンパク質アシレーションを可能にします. この非生物学的方法はグルタチオンの干渉を克服し,化学生物学と細胞内触媒の可能性を拡大します.
科学分野:
- 化学生物学
- 生物化学
- 合成化学
背景:
- 選択的タンパク質の翻訳後の改変 (PTM) は,生物学的機能を理解するために不可欠です.
- 既存の酵素学的方法は,アクセス可能なPTMの多様性を制限しています.
- アビオティック触媒は新しい非自然なPTMへの経路を提供します.
研究 の 目的:
- 生体細胞における選択的なタンパク質改変のための新しい無生物的触媒を開発する.
- グルタチオン感受性などの既存の方法の限界を克服する.
- バイオ・オートゴーナル化学におけるボロン酸-ダイオール複合体の有用性を実証する.
主な方法:
- ボロナート補助ヒドロキサム酸 (BAHA) 触媒システムの開発.
- ローカルモラリティ効果を用いて,効率的なアシルをリジン残基に変換する.
- グルタチオンに対する触媒の耐性と標的外反応性の試験
主要な成果:
- BAHA触媒システムは,ターゲットライシン残基の選択的アサイレーションを証明した.
- 触媒は低マイクロモラー反応剤濃度で効果的に機能する.
- BAHAは,一般的な生物学的干渉剤であるグルタチオンに耐性を示した.
- ヒト細胞のE. coli二酸化葉酸還元酵素に様々なアシル基を成功裏に導入した.
結論:
- BAHA触媒システムは,生物の細胞内のタンパク質に様々なアシル基を導入するための堅牢な方法を提供します.
- ボロン酸-ダイオール複合は細胞内応用のためのバイオオートゴナル反応として検証されています.
- この方法論は化学生物学と細胞内触媒のツールキットを拡張します.
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