Esterification Delivers a Functional Enzyme into a Human Cell
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 th...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/123443 |
| _version_ | 1811081878680109056 |
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| author | Ressler, Valerie T.(Valerie Terynn) Mix, Kalie Raines, Ronald T |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Ressler, Valerie T.(Valerie Terynn) Mix, Kalie Raines, Ronald T |
| author_sort | Ressler, Valerie T.(Valerie Terynn) |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:53:50Z |
| format | Article |
| id | mit-1721.1/123443 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:53:50Z |
| publishDate | 2020 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1234432022-10-01T06:48:31Z Esterification Delivers a Functional Enzyme into a Human Cell Ressler, Valerie T.(Valerie Terynn) Mix, Kalie Raines, Ronald T Massachusetts Institute of Technology. Department of Chemistry 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. National Institutes of Health (U.S.) (Grant R01GM044783) National Institutes of Health (U.S.) (Grant R01CA073808) 2020-01-14T18:46:22Z 2020-01-14T18:46:22Z 2019-03 2019-01 2020-01-07T18:13:22Z Article http://purl.org/eprint/type/JournalArticle 1554-8929 1554-8937 https://hdl.handle.net/1721.1/123443 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 en http://dx.doi.org/10.1021/acschembio.9b00033 ACS Chemical Biology 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. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Ressler, Valerie T.(Valerie Terynn) Mix, Kalie Raines, Ronald T Esterification Delivers a Functional Enzyme into a Human Cell |
| title | Esterification Delivers a Functional Enzyme into a Human Cell |
| title_full | Esterification Delivers a Functional Enzyme into a Human Cell |
| title_fullStr | Esterification Delivers a Functional Enzyme into a Human Cell |
| title_full_unstemmed | Esterification Delivers a Functional Enzyme into a Human Cell |
| title_short | Esterification Delivers a Functional Enzyme into a Human Cell |
| title_sort | esterification delivers a functional enzyme into a human cell |
| url | https://hdl.handle.net/1721.1/123443 |
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