Esterification Delivers a Functional Enzyme into a Human Cell
Esterification Delivers a Functional Enzyme into a Human Cell
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DOI：
10.1021/acschembio.9b00033
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发表时间：
2019-04-01
影响因子：
4
通讯作者：
Raines, Ronald T.
中科院分区：
文献类型：
--
作者：
Ressler, Valerie T.;Mix, Kalie A.;Raines, Ronald T.
化学生物学的一个主要障碍是将天然蛋白质递送到哺乳动物细胞的细胞质中。在此，我们报道了酶的羧基与重氮化合物的酯化不仅使其能够进入细胞质，而且还能保留其催化活性。人核糖核酸酶 1 证明了这种情况，它表现出可能具有细胞毒性的核糖核酸水解活性。内化后，新生酯被内源酯酶原位水解，使该过程无痕。这一策略为将功能性酶输送到人体细胞中提供了前所未有的机会。
A major hurdle in chemical biology is the delivery of native proteins into the cytosol of mammalian cells. Herein, we report that esterification of the carboxyl groups of an enzyme with a diazo compound enables not only its passage into the cytosol but also the retention of its catalytic activity there. This scenario is demonstrated with human ribonuclease 1, which manifests ribonucleolytic activity that can be cytotoxic. After internalization, the nascent esters are hydrolyzed in situ by endogenous esterases, making the process traceless. This strategy provides unprecedented opportunities for the delivery of functional enzymes into human cells.