Issue 25, 2024

Peptide macrocyclisation via intramolecular interception of visible-light-mediated desulfurisation

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.

Graphical abstract: Peptide macrocyclisation via intramolecular interception of visible-light-mediated desulfurisation

Supplementary files

Article information

Article type
Edge Article
Submitted
02 nov 2023
Accepted
30 apr 2024
First published
14 maj 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2024,15, 9612-9619

Peptide macrocyclisation via intramolecular interception of visible-light-mediated desulfurisation

F. R. Smith, D. Meehan, R. C. Griffiths, H. J. Knowles, P. Zhang, H. E. L. Williams, A. J. Wilson and N. J. Mitchell, Chem. Sci., 2024, 15, 9612 DOI: 10.1039/D3SC05865D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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