Abstract
Unnatural amino acids (UAAs) are important building blocks in organic synthesis and drug discovery. They are also frequently integrated into peptides or proteins for biological studies. However, the direct and simplified synthesis of UAAs remains a great challenge. At the same time, vast known peptide modifications are based on carbon-heteroatom bonds. There are no general methods for peptide modifications via the construction of C-C bonds. To address this challenge, herein we propose the LADA strategy, which is composed of two steps: the selective labeling and activation of cysteine residues, the desulfurization to generate carbon-centered radical and the radical addition to alkenes to build C-C bond. This one-pot protocol has obvious advantages such as good functional group tolerance, biocompatible reaction conditions, and retained stereochemistry. This strategy was successfully utilized for the synthesis of unnatural amino acids and direct modifications of peptides.
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Acknowledgements
This work was supported by the Shanghai Jiao Tong University (WF220417003 to Z.S.).
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Conflict of interest A patent application based on the subject matter of this manuscript has been filed to China National Intellectual Property Administration (CN 202210780183.8 and CN 202310280695.2). The authors declare no conflict of interest.
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Supporting information The supporting information is available online at https://chem.scichina.com and https://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.
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Zhou, JL., Liu, YQ. & Sun, ZK. LADA strategy for the synthesis of unnatural amino acids and direct modifications of peptides. Sci. China Chem. 66, 1788–1794 (2023). https://doi.org/10.1007/s11426-023-1605-2
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DOI: https://doi.org/10.1007/s11426-023-1605-2