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ACS Chem Biol. 2019 Apr 19;14(4):599-602. doi: 10.1021/acschembio.9b00033. Epub 2019 Mar 11.

Esterification Delivers a Functional Enzyme into a Human Cell.

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Department of Chemistry , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.


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.

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