Site-Selective Installation of Nϵ-Modified Sidechains into Peptide and Protein Scaffolds via Visible-Light-Mediated Desulfurative C–C Bond Formation

Griffiths, Rhys C.; Smith, Frances R.; Long, Jed E.; Scott, Daniel; Williams, Huw E.L.; Oldham, Neil J.; Layfield, Robert; Mitchell, Nicholas J.

Abstract

Post-translational modifications (PTMs) enhance the repertoire of protein function and mediate or influence the activity of many cellular processes. The preparation of site-specifically and homogeneously modified proteins, to apply as tools to understand the biological role of PTMs, is a challenging task. Herein, we describe a visible-light-mediated desulfurative C(sp3)–C(sp3) bond forming reaction that enables the site-selective installation of Nϵ-modified sidechains into peptides and proteins of interest. Rapid, operationally simple, and tolerant to ambient atmosphere, we demonstrate the installation of a range of lysine (Lys) PTMs into model peptide systems and showcase the potential of this technology by site-selectively installing an NϵAc sidechain into recombinantly expressed ubiquitin (Ub).

Citation

Griffiths, R. C., Smith, F. R., Long, J. E., Scott, D., Williams, H. E., Oldham, N. J., …Mitchell, N. J. (2022). Site-Selective Installation of Nϵ-Modified Sidechains into Peptide and Protein Scaffolds via Visible-Light-Mediated Desulfurative C–C Bond Formation. Angewandte Chemie International Edition, 61(2), Article e202110223. https://doi.org/10.1002/anie.202110223

• Journal Article Type: Article
• Acceptance Date: Oct 27, 2021
• Online Publication Date: Dec 3, 2021
• Publication Date: Jan 10, 2022
• Deposit Date: Feb 18, 2022
• Publicly Available Date: Feb 18, 2022
• Journal: Angewandte Chemie - International Edition
• Print ISSN: 1433-7851
• Electronic ISSN: 1521-3773
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 61
• Issue: 2
• Article Number: e202110223
• DOI: https://doi.org/10.1002/anie.202110223
• Keywords: General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/7351567
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/anie.202110223
• Related Public URLs: https://onlinelibrary.wiley.com/doi/10.1002/ange.202110223