Cysteine-Selective Modification of Peptides and Proteins via Desulfurative C−C Bond Formation

Griffiths, Rhys C.; Smith, Frances R.; Li, Diyuan; Wyatt, Jasmine; Rogers, David M; Long, Jed E.; Cusin, Lola M. L.; Tighe, Patrick J.; Layfield, Robert; Hirst, Jonathan D.; Muller, Manuel M.; Mitchell, Nicholas

Abstract

The site-selective modification of peptides and proteins facilitates the preparation of targeted therapeutic agents and tools to interrogate biochemical pathways. Among the numerous bioconjugation techniques developed to install groups of interest, those that generate C(sp3)−C(sp3) bonds are significantly underrepresented despite affording proteolytically stable, biogenic linkages. Herein, a visible-light-mediated reaction is described that enables the site-selective modification of peptides and proteins via desulfurative C(sp3)−C(sp3) bond formation. The reaction is rapid and high yielding in peptide systems, with comparable translation to proteins. Using this chemistry, a range of moieties is installed into model systems and an effective PTM-mimic is successfully integrated into a recombinantly expressed histone.

Citation

Griffiths, R. C., Smith, F. R., Li, D., Wyatt, J., Rogers, D. M., Long, J. E., Cusin, L. M. L., Tighe, P. J., Layfield, R., Hirst, J. D., Muller, M. M., & Mitchell, N. (2023). Cysteine-Selective Modification of Peptides and Proteins via Desulfurative C−C Bond Formation. Chemistry - A European Journal, 29(16), Article e202202503. https://doi.org/10.1002/chem.202202503

• Journal Article Type: Article
• Acceptance Date: Dec 16, 2022
• Online Publication Date: Feb 14, 2023
• Publication Date: Mar 16, 2023
• Deposit Date: Jan 25, 2023
• Publicly Available Date: Feb 14, 2023
• Journal: Chemistry - A European Journal
• Print ISSN: 0947-6539
• Electronic ISSN: 1521-3765
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 16
• Article Number: e202202503
• DOI: https://doi.org/10.1002/chem.202202503
• Keywords: General Chemistry; Catalysis; Organic Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/15707035
• Publisher URL: https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/chem.202202503