Site-Selective Arylation of Carboxamides from Unprotected Peptides
The amidated peptides are an important class of biologically active compounds due to their unique biological properties and wide applications as potential peptide drugs and biomarkers. Despite the abundance of free amide motifs (Asn, Gln, and C-terminal amide) in native peptides, late-stage modification of the amide unit in naturally occurring peptides remains very rare because of the intrinsically weak nucleophilicity of amides and the interference of multiple competing nucleophilic residues, which generally lead to undesired side reactions. Herein, chemoselective arylation of amides in unprotected polypeptides has been developed under an air atmosphere to afford the N-aryl amide peptides bearing various functional motifs. Its success relies on the combination of gold catalysis and silver salt to differentiate the relative inert amide among a collection of reactive nucleophilic amino acid residues (e.g., -NH2, -OH, and -COOH), favoring the C-N bond coupling toward amides over other more nucleophilic groups. Experimental and DFT studies reveal a crucial role of the silver cation, which serves as a transient coordination mask of the more reactive reaction sites, overcoming the inherently low reactivity of amides. The excellent biocompatibility of this strategy has been applied to functionalize a wide range of peptide drugs and complex peptides. The application could be further extended to peptide labeling and peptide stapling.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:145 |
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| Enthalten in: |
Journal of the American Chemical Society - 145(2023), 27 vom: 12. Juli, Seite 14865-14873 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Weipeng [VerfasserIn] |
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| Links: |
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| Themen: |
3M4G523W1G |
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| Anmerkungen: |
Date Completed 13.07.2023 Date Revised 18.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/jacs.3c03840 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM358787378 |
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| 500 | |a Date Revised 18.07.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The amidated peptides are an important class of biologically active compounds due to their unique biological properties and wide applications as potential peptide drugs and biomarkers. Despite the abundance of free amide motifs (Asn, Gln, and C-terminal amide) in native peptides, late-stage modification of the amide unit in naturally occurring peptides remains very rare because of the intrinsically weak nucleophilicity of amides and the interference of multiple competing nucleophilic residues, which generally lead to undesired side reactions. Herein, chemoselective arylation of amides in unprotected polypeptides has been developed under an air atmosphere to afford the N-aryl amide peptides bearing various functional motifs. Its success relies on the combination of gold catalysis and silver salt to differentiate the relative inert amide among a collection of reactive nucleophilic amino acid residues (e.g., -NH2, -OH, and -COOH), favoring the C-N bond coupling toward amides over other more nucleophilic groups. Experimental and DFT studies reveal a crucial role of the silver cation, which serves as a transient coordination mask of the more reactive reaction sites, overcoming the inherently low reactivity of amides. The excellent biocompatibility of this strategy has been applied to functionalize a wide range of peptide drugs and complex peptides. The application could be further extended to peptide labeling and peptide stapling | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a 3M4G523W1G |2 NLM | |
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| 650 | 7 | |a Amides |2 NLM | |
| 650 | 7 | |a Amino Acids |2 NLM | |
| 700 | 1 | |a Chen, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yinghan |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Siyu |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Wenju |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Chengjian |e verfasserin |4 aut | |
| 700 | 1 | |a Houk, K N |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Jin |e verfasserin |4 aut | |
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