A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling
We report the discovery of a facile transformation between perfluoroaromatic molecules and a cysteine thiolate, which is arylated at room temperature. This new approach enabled us to selectively modify cysteine residues in unprotected peptides, providing access to variants containing rigid perfluoro...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Chemical Society (ACS)
2015
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| Online Access: | http://hdl.handle.net/1721.1/95630 https://orcid.org/0000-0002-0511-4280 |
| _version_ | 1826209283926130688 |
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| author | Spokoyny, Alexander M. Zou, Yekui Yu, Hongtao Lin, Yu-Shan Pentelute, Bradley L. Ling, Jingjing |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Spokoyny, Alexander M. Zou, Yekui Yu, Hongtao Lin, Yu-Shan Pentelute, Bradley L. Ling, Jingjing |
| author_sort | Spokoyny, Alexander M. |
| collection | MIT |
| description | We report the discovery of a facile transformation between perfluoroaromatic molecules and a cysteine thiolate, which is arylated at room temperature. This new approach enabled us to selectively modify cysteine residues in unprotected peptides, providing access to variants containing rigid perfluoroaromatic staples. This stapling modification performed on a peptide sequence designed to bind the C-terminal domain of an HIV-1 capsid assembly polyprotein (C-CA) showed enhancement in binding, cell permeability, and proteolytic stability properties, as compared to the unstapled analog. Importantly, chemical stability of the formed staples allowed us to use this motif in the native chemical ligation-mediated synthesis of a small protein affibody that is capable of binding the human epidermal growth factor 2 receptor. |
| first_indexed | 2024-09-23T14:20:05Z |
| format | Article |
| id | mit-1721.1/95630 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:20:05Z |
| publishDate | 2015 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/956302022-10-01T20:39:38Z A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling Spokoyny, Alexander M. Zou, Yekui Yu, Hongtao Lin, Yu-Shan Pentelute, Bradley L. Ling, Jingjing Massachusetts Institute of Technology. Department of Chemistry Spokoyny, Alexander M. Zou, Yekui Ling, Jingjing Pentelute, Bradley L. We report the discovery of a facile transformation between perfluoroaromatic molecules and a cysteine thiolate, which is arylated at room temperature. This new approach enabled us to selectively modify cysteine residues in unprotected peptides, providing access to variants containing rigid perfluoroaromatic staples. This stapling modification performed on a peptide sequence designed to bind the C-terminal domain of an HIV-1 capsid assembly polyprotein (C-CA) showed enhancement in binding, cell permeability, and proteolytic stability properties, as compared to the unstapled analog. Importantly, chemical stability of the formed staples allowed us to use this motif in the native chemical ligation-mediated synthesis of a small protein affibody that is capable of binding the human epidermal growth factor 2 receptor. National Institutes of Health (U.S.) (GM046059) National Institutes of Health (U.S.) (GM101762) MIT Faculty Start-up Fund Singapore. Agency for Science, Technology and Research (National Science Scholarship) National Cancer Institute (U.S.) (P30-CA14051) 2015-02-25T20:23:16Z 2015-02-25T20:23:16Z 2013-04 2013-01 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/95630 Spokoyny, Alexander M., Yekui Zou, Jingjing J. Ling, Hongtao Yu, Yu-Shan Lin, and Bradley L. Pentelute. “ A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling .” Journal of the American Chemical Society 135, no. 16 (April 24, 2013): 5946–5949. https://orcid.org/0000-0002-0511-4280 en_US http://dx.doi.org/10.1021/ja400119t 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 (ACS) PMC |
| spellingShingle | Spokoyny, Alexander M. Zou, Yekui Yu, Hongtao Lin, Yu-Shan Pentelute, Bradley L. Ling, Jingjing A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling |
| title | A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling |
| title_full | A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling |
| title_fullStr | A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling |
| title_full_unstemmed | A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling |
| title_short | A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling |
| title_sort | perfluoroaryl cysteine s subscript n ar chemistry approach to unprotected peptide stapling |
| url | http://hdl.handle.net/1721.1/95630 https://orcid.org/0000-0002-0511-4280 |
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