Synthesis of Polypeptides with High-Fidelity Terminal Functionalities under NCA Monomer-Starved Conditions
Controlled polypeptide synthesis via α-amino acid N-carboxylic anhydride (NCA) polymerization using conventional primary amine initiators encounters two major obstacles: (i) normal amine mechanism (NAM) and activated monomer mechanism (AMM) coexist due to amine basicity and nucleophilicity and (ii)...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2021-01-01
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| Series: | Research |
| Online Access: | http://dx.doi.org/10.34133/2021/9826046 |
| _version_ | 1797287785689776128 |
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| author | Lei Li Jie Cen Wenhao Pan Yuben Zhang Xuanxi Leng Zhengqi Tan Hao Yin Shiyong Liu |
| author_facet | Lei Li Jie Cen Wenhao Pan Yuben Zhang Xuanxi Leng Zhengqi Tan Hao Yin Shiyong Liu |
| author_sort | Lei Li |
| collection | DOAJ |
| description | Controlled polypeptide synthesis via α-amino acid N-carboxylic anhydride (NCA) polymerization using conventional primary amine initiators encounters two major obstacles: (i) normal amine mechanism (NAM) and activated monomer mechanism (AMM) coexist due to amine basicity and nucleophilicity and (ii) NCA is notoriously sensitive towards moisture and heat and unstable upon storage. We serendipitously discover that N-phenoxycarbonyl-functionalized α-amino acid (NPCA), a latent NCA precursor, could be polymerized solely based on NAM with high initiating efficiency by using primary amine hydrochloride as an initiator. The polymerization affords well-defined polypeptides with narrow polydispersity and high-fidelity terminal functionalities, as revealed by the clean set of MALDI-TOF MS patterns. We further demonstrate successful syntheses of random and block copolypeptides, even under open-vessel conditions. Overall, the integration of moisture-insensitive and air-tolerant NPCA precursors with stable primary amine hydrochloride initiators represents a general strategy for controlled synthesis of high-fidelity polypeptides with sophisticated functions. |
| first_indexed | 2024-03-07T18:38:53Z |
| format | Article |
| id | doaj.art-fdd4b9990a01414e8b470d074ea53dfa |
| institution | Directory Open Access Journal |
| issn | 2639-5274 |
| language | English |
| last_indexed | 2024-03-07T18:38:53Z |
| publishDate | 2021-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj.art-fdd4b9990a01414e8b470d074ea53dfa2024-03-02T04:32:34ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742021-01-01202110.34133/2021/9826046Synthesis of Polypeptides with High-Fidelity Terminal Functionalities under NCA Monomer-Starved ConditionsLei Li0Jie Cen1Wenhao Pan2Yuben Zhang3Xuanxi Leng4Zhengqi Tan5Hao Yin6Shiyong Liu7Hefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaHefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaHefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaHefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaHefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaHefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaMass Spectrometry Lab, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026, ChinaHefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaControlled polypeptide synthesis via α-amino acid N-carboxylic anhydride (NCA) polymerization using conventional primary amine initiators encounters two major obstacles: (i) normal amine mechanism (NAM) and activated monomer mechanism (AMM) coexist due to amine basicity and nucleophilicity and (ii) NCA is notoriously sensitive towards moisture and heat and unstable upon storage. We serendipitously discover that N-phenoxycarbonyl-functionalized α-amino acid (NPCA), a latent NCA precursor, could be polymerized solely based on NAM with high initiating efficiency by using primary amine hydrochloride as an initiator. The polymerization affords well-defined polypeptides with narrow polydispersity and high-fidelity terminal functionalities, as revealed by the clean set of MALDI-TOF MS patterns. We further demonstrate successful syntheses of random and block copolypeptides, even under open-vessel conditions. Overall, the integration of moisture-insensitive and air-tolerant NPCA precursors with stable primary amine hydrochloride initiators represents a general strategy for controlled synthesis of high-fidelity polypeptides with sophisticated functions.http://dx.doi.org/10.34133/2021/9826046 |
| spellingShingle | Lei Li Jie Cen Wenhao Pan Yuben Zhang Xuanxi Leng Zhengqi Tan Hao Yin Shiyong Liu Synthesis of Polypeptides with High-Fidelity Terminal Functionalities under NCA Monomer-Starved Conditions Research |
| title | Synthesis of Polypeptides with High-Fidelity Terminal Functionalities under NCA Monomer-Starved Conditions |
| title_full | Synthesis of Polypeptides with High-Fidelity Terminal Functionalities under NCA Monomer-Starved Conditions |
| title_fullStr | Synthesis of Polypeptides with High-Fidelity Terminal Functionalities under NCA Monomer-Starved Conditions |
| title_full_unstemmed | Synthesis of Polypeptides with High-Fidelity Terminal Functionalities under NCA Monomer-Starved Conditions |
| title_short | Synthesis of Polypeptides with High-Fidelity Terminal Functionalities under NCA Monomer-Starved Conditions |
| title_sort | synthesis of polypeptides with high fidelity terminal functionalities under nca monomer starved conditions |
| url | http://dx.doi.org/10.34133/2021/9826046 |
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