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Esterification Delivers a Functional Enzyme into a Human Cell

Author(s)
Ressler, Valerie T.(Valerie Terynn); Mix, Kalie; Raines, Ronald T
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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.
Date issued
2019-03
URI
https://hdl.handle.net/1721.1/123443
Department
Massachusetts Institute of Technology. Department of Chemistry
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
ISSN
1554-8929
1554-8937

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