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., Layfield, R., & 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