Synthesis of proteins by automated flow chemistry
Ribosomes can produce proteins in minutes and are largely constrained to proteinogenic amino acids. Here, we report highly efficient chemistry matched with an automated fast-flow instrument for the direct manufacturing of peptide chains up to 164 amino acids long over 327 consecutive reactions. The...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2020
|
| Online Access: | https://hdl.handle.net/1721.1/128762 |
| _version_ | 1826209468997697536 |
|---|---|
| author | Hartrampf, Nina Saebi, Azin Poskus, M. Gates, Zachary P Callahan, A. J. Cowfer, A. E. Hanna, S. Antilla, S. Schissel, Carly K. Quartararo, Anthony James Ye, Xiyun Mijalis, Alexander James Simon, M. D. Loas, Andrei Ioan Liu, S. Jessen, C. Nielsen, T. E. Pentelute, Bradley L. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Hartrampf, Nina Saebi, Azin Poskus, M. Gates, Zachary P Callahan, A. J. Cowfer, A. E. Hanna, S. Antilla, S. Schissel, Carly K. Quartararo, Anthony James Ye, Xiyun Mijalis, Alexander James Simon, M. D. Loas, Andrei Ioan Liu, S. Jessen, C. Nielsen, T. E. Pentelute, Bradley L. |
| author_sort | Hartrampf, Nina |
| collection | MIT |
| description | Ribosomes can produce proteins in minutes and are largely constrained to proteinogenic amino acids. Here, we report highly efficient chemistry matched with an automated fast-flow instrument for the direct manufacturing of peptide chains up to 164 amino acids long over 327 consecutive reactions. The machine is rapid: Peptide chain elongation is complete in hours. We demonstrate the utility of this approach by the chemical synthesis of nine different protein chains that represent enzymes, structural units, and regulatory factors. After purification and folding, the synthetic materials display biophysical and enzymatic properties comparable to the biologically expressed proteins. High-fidelity automated flow chemistry is an alternative for producing single-domain proteins without the ribosome. |
| first_indexed | 2024-09-23T14:23:00Z |
| format | Article |
| id | mit-1721.1/128762 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:23:00Z |
| publishDate | 2020 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1287622022-10-01T21:00:19Z Synthesis of proteins by automated flow chemistry Hartrampf, Nina Saebi, Azin Poskus, M. Gates, Zachary P Callahan, A. J. Cowfer, A. E. Hanna, S. Antilla, S. Schissel, Carly K. Quartararo, Anthony James Ye, Xiyun Mijalis, Alexander James Simon, M. D. Loas, Andrei Ioan Liu, S. Jessen, C. Nielsen, T. E. Pentelute, Bradley L. Massachusetts Institute of Technology. Department of Chemistry Ribosomes can produce proteins in minutes and are largely constrained to proteinogenic amino acids. Here, we report highly efficient chemistry matched with an automated fast-flow instrument for the direct manufacturing of peptide chains up to 164 amino acids long over 327 consecutive reactions. The machine is rapid: Peptide chain elongation is complete in hours. We demonstrate the utility of this approach by the chemical synthesis of nine different protein chains that represent enzymes, structural units, and regulatory factors. After purification and folding, the synthetic materials display biophysical and enzymatic properties comparable to the biologically expressed proteins. High-fidelity automated flow chemistry is an alternative for producing single-domain proteins without the ribosome. National Science Foundation (Grant 1122374) 2020-12-09T21:01:13Z 2020-12-09T21:01:13Z 2020-05 2020-02 2020-09-18T15:40:24Z Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 https://hdl.handle.net/1721.1/128762 Hartrampf, N. et al. "Synthesis of proteins by automated flow chemistry." Science 368, 6494 (February 2020): 980-987 © 2020 American Association for the Advancement of Science en http://dx.doi.org/10.1126/science.abb2491 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) chemRxiv |
| spellingShingle | Hartrampf, Nina Saebi, Azin Poskus, M. Gates, Zachary P Callahan, A. J. Cowfer, A. E. Hanna, S. Antilla, S. Schissel, Carly K. Quartararo, Anthony James Ye, Xiyun Mijalis, Alexander James Simon, M. D. Loas, Andrei Ioan Liu, S. Jessen, C. Nielsen, T. E. Pentelute, Bradley L. Synthesis of proteins by automated flow chemistry |
| title | Synthesis of proteins by automated flow chemistry |
| title_full | Synthesis of proteins by automated flow chemistry |
| title_fullStr | Synthesis of proteins by automated flow chemistry |
| title_full_unstemmed | Synthesis of proteins by automated flow chemistry |
| title_short | Synthesis of proteins by automated flow chemistry |
| title_sort | synthesis of proteins by automated flow chemistry |
| url | https://hdl.handle.net/1721.1/128762 |
| work_keys_str_mv | AT hartrampfnina synthesisofproteinsbyautomatedflowchemistry AT saebiazin synthesisofproteinsbyautomatedflowchemistry AT poskusm synthesisofproteinsbyautomatedflowchemistry AT gateszacharyp synthesisofproteinsbyautomatedflowchemistry AT callahanaj synthesisofproteinsbyautomatedflowchemistry AT cowferae synthesisofproteinsbyautomatedflowchemistry AT hannas synthesisofproteinsbyautomatedflowchemistry AT antillas synthesisofproteinsbyautomatedflowchemistry AT schisselcarlyk synthesisofproteinsbyautomatedflowchemistry AT quartararoanthonyjames synthesisofproteinsbyautomatedflowchemistry AT yexiyun synthesisofproteinsbyautomatedflowchemistry AT mijalisalexanderjames synthesisofproteinsbyautomatedflowchemistry AT simonmd synthesisofproteinsbyautomatedflowchemistry AT loasandreiioan synthesisofproteinsbyautomatedflowchemistry AT lius synthesisofproteinsbyautomatedflowchemistry AT jessenc synthesisofproteinsbyautomatedflowchemistry AT nielsente synthesisofproteinsbyautomatedflowchemistry AT pentelutebradleyl synthesisofproteinsbyautomatedflowchemistry |