One-pot iterative native chemical ligation–desulfurisation chemistry leveraging a coumarin-based photolabile protecting group for cysteine
An iterative one-pot peptide native chemical ligation (NCL)–desulfurisation strategy, featuring 7-diethylamino-3-methyl coumarin (DEAMC) as an orthogonal protecting group for cysteine, is described. We show that selective desulfurisation of unprotected cysteine residues can be achieved in the presence of DEAMC-protected cysteine residues, allowing subsequent DEAMC photodeprotection and native chemical ligation to be performed without purification. The efficiency of this approach was exemplified through the one-pot synthesis of a 60-residue mucin-1 peptide.
Authors
- Timothy S. Chisholm (ORCID: https://orcid.org/0000-0002-8693-3797)
- Richard J. Payne (ORCID: https://orcid.org/0000-0002-3618-9226)
- Sameer S. Kulkarni (ORCID: https://orcid.org/0000-0001-5896-9568)
- Peter H. G. Egelund (ORCID: https://orcid.org/0000-0001-5392-4862)
- Lucas Kambanis (ORCID: https://orcid.org/0000-0001-8278-5363)
Institutions
- The University of Sydney (AU)
- Australian Research Council (AU)
- ARC Centre of Excellence for Innovations in Peptide and Protein Science (AU)
- Human Growth Foundation (US)
Publication Details
- Journal
- Australian Journal of Chemistry
- Published
- 2025-09-23
- DOI
- https://doi.org/10.1071/ch25124
- Citations
- 1
- Primary Topic
- Sulfur-Based Synthesis Techniques
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- University of Sydney