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.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
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).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author declares no competing interests.
Rights and permissions
About this article
Cite this article
Chen, FJ. Another side of side chains. Nat Rev Chem (2024). https://doi.org/10.1038/s41570-024-00609-y
Published:
DOI: https://doi.org/10.1038/s41570-024-00609-y
