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Updated: Jun 22, 2025

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
Published on: August 1, 2018
Peptide macrocyclisation via intramolecular interception of visible-light-mediated desulfurisation
Frances R Smith1, Declan Meehan1, Rhys C Griffiths1
1School of Chemistry, University of Nottingham, University Park Nottingham NG7 2RD UK nicholas.mitchell@nottingham.ac.uk.
Abstract:
Synthetic methods that enable the macrocyclisation of peptides facilitate the development of effective therapeutic and diagnostic tools. Herein we report a peptide cyclisation strategy based on intramolecular interception of visible-light-mediated cysteine desulfurisation. This method allows cyclisation of unprotected peptides in an aqueous solution via the installation of a hydrocarbon linkage. We explore the limits of this chemistry using a range of model peptides of increasing length and complexity, including peptides of biological/therapeutic relevance. The method is applied to replace the native disulfide of the peptide hormone, oxytocin, with a proteolytically/redox-stable hydrocarbon, and internal macrocyclisation of an MCL-1-binding peptide.
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