A cell-penetrating artificial metalloenzyme regulates a gene switch in a designer mammalian cell

DOI DOI DOI HANDLE PDF ほか2件をすべて表示 一部だけ表示 被引用文献12件 オープンアクセス

書誌事項

公開日
2018-05-16
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/s41467-018-04440-0
  • 10.5451/unibas-ep70534
  • 10.3929/ethz-b-000265945
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title> <jats:p>Complementing enzymes in their native environment with either homogeneous or heterogeneous catalysts is challenging due to the sea of functionalities present within a cell. To supplement these efforts, artificial metalloenzymes are drawing attention as they combine attractive features of both homogeneous catalysts and enzymes. Herein we show that such hybrid catalysts consisting of a metal cofactor, a cell-penetrating module, and a protein scaffold are taken up into HEK-293T cells where they catalyze the uncaging of a hormone. This bioorthogonal reaction causes the upregulation of a gene circuit, which in turn leads to the expression of a nanoluc-luciferase. Relying on the biotin–streptavidin technology, variation of the biotinylated ruthenium complex: the biotinylated cell-penetrating poly(disulfide) ratio can be combined with point mutations on streptavidin to optimize the catalytic uncaging of an allyl-carbamate-protected thyroid hormone triiodothyronine. These results demonstrate that artificial metalloenzymes offer highly modular tools to perform bioorthogonal catalysis in live HEK cells.</jats:p>

収録刊行物

  • Nature Communications

    Nature Communications 9 (1), 1943-, 2018-05-16

    Springer Science and Business Media LLC

被引用文献 (12)*注記

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