Peptide stapling has traditionally relied on the incorporation of unnatural amino acids and symmetric stapling. A recent article targets a typically inert C–H bond within the serine side chain, offering new avenues for conformational control and side chain engineering.
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References
Blackwell, H. E. & Grubbs, R. H. Highly efficient synthesis of covalently cross-linked peptide helices by ring-closing metathesis. Angew. Chem. Int. Ed. 37, 3281–3284 (1998).
Walensky, L. D. et al. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305, 1466–1470 (2004).
Lau, Y. H., de Andrade, P., Wu, Y. & Spring, D. R. Peptide stapling techniques based on different macrocyclisation chemistries. Chem. Soc. Rev. 44, 91–102 (2015).
Chen, F.-J., Lin, W. & Chen, F.-E. Non-symmetric stapling of native peptides. Nat. Rev. Chem. https://doi.org/10.1038/s41570-024-00591-5 (2024).
Kubota, K., Dai, P., Pentelute, B. L. & Buchwald, S. L. Palladium oxidative addition complexes for peptide and protein cross-linking. J. Am. Chem. Soc. 140, 3128–3133 (2018).
Li, B. et al. Cooperative stapling of native peptides at lysine and tyrosine or arginine with formaldehyde. Angew. Chem. Int. Ed. 60, 6646–6652 (2021).
Chen, F. J., Pinnette, N., Yang, F. & Gao, J. A cysteine-directed proximity-driven crosslinking method for native peptide bicyclization. Angew. Chem. Int. Ed. 62, e202306813 (2023).
Ceballos, J., Grinhagena, E., Sangouard, G., Heinis, C. & Waser, J. Cys–cys and cys–lys stapling of unprotected peptides enabled by hypervalent iodine reagents. Angew. Chem. Int. Ed. 60, 9022–9031 (2021).
Wang, M. et al. Site-selective polyfluoroaryl modification and unsymmetric stapling of unprotected peptides. J. Am. Chem. Soc. 146, 6675–6685 (2024).
Twilton, J. et al. Selective hydrogen atom abstraction through induced bond polarization: Direct α-arylation of alcohols through photoredox, hat, and nickel catalysis. Angew. Chem. Int. Ed. 57, 5369–5373 (2018).
Spokoyny, A. M. et al. A perfluoroaryl-cysteine snar chemistry approach to unprotected peptide stapling. J. Am. Chem. Soc. 135, 5946–5949 (2013).
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Chen, FJ. Another side of side chains. Nat Rev Chem (2024). https://doi.org/10.1038/s41570-024-00609-y
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DOI: https://doi.org/10.1038/s41570-024-00609-y