Accelerated protein synthesis via one–pot ligation–deselenization chemistry
Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at β-selenoaspartate and γ-selenoglutamate that enables the generation of native polypeptide products on un...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Elsevier
2017
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| Online Access: | https://eprints.nottingham.ac.uk/42867/ |
| _version_ | 1848796588689850368 |
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| author | Mitchell, Nicholas J. Sayers, Jessica Kulkarni, Sameer S. Clayton, Daniel Goldys, Anna M. Ripoll-Rozada, Jorge Barbosa Pereira, Pedro José Chan, Bun Radom, Leo Payne, Richard J. |
| author_facet | Mitchell, Nicholas J. Sayers, Jessica Kulkarni, Sameer S. Clayton, Daniel Goldys, Anna M. Ripoll-Rozada, Jorge Barbosa Pereira, Pedro José Chan, Bun Radom, Leo Payne, Richard J. |
| author_sort | Mitchell, Nicholas J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at β-selenoaspartate and γ-selenoglutamate that enables the generation of native polypeptide products on unprecedented timescales. The deselenization step is chemoselective in the presence of unprotected selenocysteine, which is highlighted in the synthesis of selenoprotein K. The power of the methodology is also showcased through the synthesis of three tick-derived thrombin-inhibiting proteins, each of which were assembled, purified, and isolated for biological assays within a few hours. The methodology described here should serve as a powerful means of accessing synthetic proteins, including therapeutic leads, in the future. |
| first_indexed | 2025-11-14T19:50:22Z |
| format | Article |
| id | nottingham-42867 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:50:22Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-428672020-05-04T18:45:30Z https://eprints.nottingham.ac.uk/42867/ Accelerated protein synthesis via one–pot ligation–deselenization chemistry Mitchell, Nicholas J. Sayers, Jessica Kulkarni, Sameer S. Clayton, Daniel Goldys, Anna M. Ripoll-Rozada, Jorge Barbosa Pereira, Pedro José Chan, Bun Radom, Leo Payne, Richard J. Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at β-selenoaspartate and γ-selenoglutamate that enables the generation of native polypeptide products on unprecedented timescales. The deselenization step is chemoselective in the presence of unprotected selenocysteine, which is highlighted in the synthesis of selenoprotein K. The power of the methodology is also showcased through the synthesis of three tick-derived thrombin-inhibiting proteins, each of which were assembled, purified, and isolated for biological assays within a few hours. The methodology described here should serve as a powerful means of accessing synthetic proteins, including therapeutic leads, in the future. Elsevier 2017-05-11 Article PeerReviewed Mitchell, Nicholas J., Sayers, Jessica, Kulkarni, Sameer S., Clayton, Daniel, Goldys, Anna M., Ripoll-Rozada, Jorge, Barbosa Pereira, Pedro José, Chan, Bun, Radom, Leo and Payne, Richard J. (2017) Accelerated protein synthesis via one–pot ligation–deselenization chemistry. Chem, 2 (5). pp. 703-715. ISSN 2451-9294 peptide synthesis; selenium; proteins; quantum chemistry calculations http://www.sciencedirect.com/science/article/pii/S2451929417301699 doi:10.1016/j.chempr.2017.04.003 doi:10.1016/j.chempr.2017.04.003 |
| spellingShingle | peptide synthesis; selenium; proteins; quantum chemistry calculations Mitchell, Nicholas J. Sayers, Jessica Kulkarni, Sameer S. Clayton, Daniel Goldys, Anna M. Ripoll-Rozada, Jorge Barbosa Pereira, Pedro José Chan, Bun Radom, Leo Payne, Richard J. Accelerated protein synthesis via one–pot ligation–deselenization chemistry |
| title | Accelerated protein synthesis via one–pot ligation–deselenization chemistry |
| title_full | Accelerated protein synthesis via one–pot ligation–deselenization chemistry |
| title_fullStr | Accelerated protein synthesis via one–pot ligation–deselenization chemistry |
| title_full_unstemmed | Accelerated protein synthesis via one–pot ligation–deselenization chemistry |
| title_short | Accelerated protein synthesis via one–pot ligation–deselenization chemistry |
| title_sort | accelerated protein synthesis via one–pot ligation–deselenization chemistry |
| topic | peptide synthesis; selenium; proteins; quantum chemistry calculations |
| url | https://eprints.nottingham.ac.uk/42867/ https://eprints.nottingham.ac.uk/42867/ https://eprints.nottingham.ac.uk/42867/ |