Esterification Delivers a Functional Enzyme into a Human Cell
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nihms-1017095.pdf
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Accepted version
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651.38 KB
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Author(s) • •
Ressler, Valerie T.(Valerie Terynn)
Mix, Kalie
Raines, Ronald T
Date Issued
March 2019
Journal
ACS Chemical Biology
Publisher
American Chemical Society (ACS)
Citation
Ressler, Valerie T. et al. "Esterification Delivers a Functional Enzyme into a Human Cell." ACS Chemical Biology 14, 4 (March 2019): 599-602 © 2019 American Chemical Society
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/acschembio.9b00033