選択的にヒトサイトクロームP450 2J2を検出するための近赤外線光探査機の構築のための分子設計戦略
Jing Ning1,2, Tao Liu2, Peipei Dong1
1College of Integrative Medicine, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, College of Pharmacy , Dalian Medical University , Dalian 116044 , China.
Journal of the American Chemical Society
|December 12, 2018
まとめ
研究者は,シトクロームP450 2J2 (CYP2J2) 酵素の活性をリアルタイムでモニタリングするための新しい光探査機BnXPIを開発しました. このツールは,CYP2J2の理解を向上させます.
科学分野:
- 生物化学
- 分子生物学
- 化学生物学
背景:
- サイトクロームP450 2J2 (CYP2J2) は,異種生物および内生化合物の代謝に不可欠であり,様々な生理学的および病理学的プロセスに影響を与えます.
- 腫瘍形成と癌診断におけるCYP2J2の役割は,リアルタイムのモニタリングツールがないため,十分に理解されていません.
研究 の 目的:
- 生物学的システムにおけるCYP2J2活動のリアルタイムモニタリングのための分子ツールを開発する.
- 腫瘍形成におけるCYP2J2の生物学的機能を調査する.
主な方法:
- 近赤外線フッ素を用いたCYP2J2選択性光プローブ (HXPI) を作成するために,分子設計原理が用いられました.
- 自燃結合剤は,CYP2J2の狭い基板チャネルに対する反応性と特異性を高めるために,HXPI誘導体に組み込まれました.
- BnXPIは,O-アルキル化HXPI誘導体であり,スクリーニング後に最適な探査物として特定されました.
主要な成果:
- BnXPIは,CYP2J2を in vitro および in vivo で検出するための高い特異性,感度,および適用性を示した.
- CYP2J2によるO- 脱メチル化により,BnXPIは自己燃焼反応を起こし,HXPIを放出し,リアルタイムに光をモニタリングすることができる.
- BnXPIは,細胞,腫瘍組織,および腫瘍を持つ動物を含む生体系におけるCYP2J2活性を成功的にモニターした.
結論:
- CYP2J2のモニタリングに高度に特異的で広く適用可能なツールを開発するための実用的な戦略が確立されました.
- BnXPIは,腫瘍形成と癌診断におけるCYP2J2の生物学的な機能を探求するための有望なツールです.
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