Cytosolic Delivery of Proteins by Bioreversible Esterification
Cloaking its carboxyl groups with a hydrophobic moiety is shown to enable a protein to enter the cytosol of a mammalian cell. Diazo compounds derived from (p-methylphenyl)glycine were screened for the ability to esterify the green fluorescent protein (GFP) in an aqueous environment. Esterification o...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society
2018
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| Online Access: | http://hdl.handle.net/1721.1/118315 https://orcid.org/0000-0002-2836-5744 https://orcid.org/0000-0001-7164-1719 |
| _version_ | 1826193505485062144 |
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| author | Lomax, Jo E. Mix, Kalie Raines, Ronald T |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Lomax, Jo E. Mix, Kalie Raines, Ronald T |
| author_sort | Lomax, Jo E. |
| collection | MIT |
| description | Cloaking its carboxyl groups with a hydrophobic moiety is shown to enable a protein to enter the cytosol of a mammalian cell. Diazo compounds derived from (p-methylphenyl)glycine were screened for the ability to esterify the green fluorescent protein (GFP) in an aqueous environment. Esterification of GFP with 2-diazo-2-(p-methylphenyl)-N,N-dimethylacetamide was efficient. The esterified protein entered the cytosol by traversing the plasma membrane directly, like a small-molecule prodrug. As with prodrugs, the nascent esters are substrates for endogenous esterases, which regenerate native protein. Thus, esterification could provide a general means to deliver native proteins to the cytosol. |
| first_indexed | 2024-09-23T09:40:14Z |
| format | Article |
| id | mit-1721.1/118315 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:40:14Z |
| publishDate | 2018 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/1183152022-09-30T16:06:39Z Cytosolic Delivery of Proteins by Bioreversible Esterification Lomax, Jo E. Mix, Kalie Raines, Ronald T Massachusetts Institute of Technology. Department of Chemistry Raines, Ronald T. Mix, Kalie Raines, Ronald T Cloaking its carboxyl groups with a hydrophobic moiety is shown to enable a protein to enter the cytosol of a mammalian cell. Diazo compounds derived from (p-methylphenyl)glycine were screened for the ability to esterify the green fluorescent protein (GFP) in an aqueous environment. Esterification of GFP with 2-diazo-2-(p-methylphenyl)-N,N-dimethylacetamide was efficient. The esterified protein entered the cytosol by traversing the plasma membrane directly, like a small-molecule prodrug. As with prodrugs, the nascent esters are substrates for endogenous esterases, which regenerate native protein. Thus, esterification could provide a general means to deliver native proteins to the cytosol. National Institutes of Health (U.S.) (Molecular Biosciences Training Grant T32 GM007215) National Institutes of Health (U.S.) (R01 GM044783) 2018-10-01T17:19:24Z 2018-10-01T17:19:24Z 2017-10 2017-06 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/118315 Mix, Kalie A., et al. “Cytosolic Delivery of Proteins by Bioreversible Esterification.” Journal of the American Chemical Society, vol. 139, no. 41, Oct. 2017, pp. 14396–98 https://orcid.org/0000-0002-2836-5744 https://orcid.org/0000-0001-7164-1719 en_US http://dx.doi.org/10.1021/jacs.7b06597 Journal of the American Chemical Society 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 Prof. Raines |
| spellingShingle | Lomax, Jo E. Mix, Kalie Raines, Ronald T Cytosolic Delivery of Proteins by Bioreversible Esterification |
| title | Cytosolic Delivery of Proteins by Bioreversible Esterification |
| title_full | Cytosolic Delivery of Proteins by Bioreversible Esterification |
| title_fullStr | Cytosolic Delivery of Proteins by Bioreversible Esterification |
| title_full_unstemmed | Cytosolic Delivery of Proteins by Bioreversible Esterification |
| title_short | Cytosolic Delivery of Proteins by Bioreversible Esterification |
| title_sort | cytosolic delivery of proteins by bioreversible esterification |
| url | http://hdl.handle.net/1721.1/118315 https://orcid.org/0000-0002-2836-5744 https://orcid.org/0000-0001-7164-1719 |
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