バイオにおける多標的タンパク質残留物に対する光化キノンメチドの遺伝的エンコーディング
Jun Liu1, Shanshan Li1,2, Nayyar A Aslam3
1Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute , University of California San Francisco , 555 Mission Bay Boulevard South , San Francisco , California 94158 , United States.
Journal of the American Chemical Society
|June 12, 2019
まとめ
研究者らは,光活性化時にタンパク質に共性結合を形成する新しい非自然なアミノ酸 (FnbY) を開発した. この方法は9つの天然のアミノ酸残基を標的とし タンパク質工学と生物治療の可能性を広げています
科学分野:
- 生物化学
- 分子生物学
- タンパク質工学
背景:
- 遺伝的にコードされた非自然なアミノ酸 (UAAs) は,インビボタンパク質の改変を可能にします.
- 現在のUAAは残留特異性が限られており,応用が制限されています.
研究 の 目的:
- 遺伝子コードで新しいUaa,FnbYを in vivoでタンパク質を共性的に改変する.
- UAASが対象とする天然アミノ酸残基の範囲を拡大する.
主な方法:
- 大腸菌と哺乳類の細胞におけるFnbYの遺伝的エンコーディング
- FnbYを光活性化して反応性キノンメチド (QM) を生成する.
- タンパク質の様々な天然アミノ酸残留物とのQM反応性の分析.
主要な成果:
- FnbYは生体細胞で成功裏にエンコードされ,光活性化されました.
- 光活性化されたFnbYは,Cys,Lys,His,Tyr,Trp,Met,Arg,Asn,Glnの9つの自然残基をターゲットにした.
- FnbYは既存の方法よりも高いクロスリンク効率と寿命の長い中間材料を示した.
結論:
- FnbYは,in vivoの共性タンパク質標的化のための残留物のレパートリーを大幅に拡張します.
- FnbYの光活性化,マルチターゲティングは化学生物学,生物療法,タンパク質工学で広く利用できます.
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