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

Autor:	Smith FR; School of Chemistry, University of Nottingham, University Park Nottingham NG7 2RD UK nicholas.mitchell@nottingham.ac.uk., Meehan D; School of Chemistry, University of Nottingham, University Park Nottingham NG7 2RD UK nicholas.mitchell@nottingham.ac.uk., Griffiths RC; School of Chemistry, University of Nottingham, University Park Nottingham NG7 2RD UK nicholas.mitchell@nottingham.ac.uk., Knowles HJ; School of Chemistry, University of Nottingham, University Park Nottingham NG7 2RD UK nicholas.mitchell@nottingham.ac.uk., Zhang P; School of Chemistry, University of Leeds Woodhouse Lane Leeds LS2 9JT UK., Williams HEL; Biodiscovery Institute, University of Nottingham, University Park Nottingham NG7 2RD UK., Wilson AJ; School of Chemistry, University of Leeds Woodhouse Lane Leeds LS2 9JT UK.; School of Chemistry, University of Birmingham Edgbaston Birmingham B15 2TT UK., Mitchell NJ; School of Chemistry, University of Nottingham, University Park Nottingham NG7 2RD UK nicholas.mitchell@nottingham.ac.uk.
Jazyk:	angličtina
Zdroj:	Chemical science [Chem Sci] 2024 May 14; Vol. 15 (25), pp. 9612-9619. Date of Electronic Publication: 2024 May 14 (Print Publication: 2024).
DOI:	10.1039/d3sc05865d
Abstrakt:	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. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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