Site‐Selective Installation of N<sup><i>ϵ</i></sup>‐Modified Sidechains into Peptide and Protein Scaffolds via Visible‐Light‐Mediated Desulfurative C–C Bond Formation
Rhys C. Griffiths, Frances R. Smith, Jed Long, Daniel Scott, Huw E. L. Williams, Neil J. Oldham, Robert Layfield, Nicholas J. Mitchell
Abstract
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(sp 3 )–C(sp 3 ) bond forming reaction that enables the site‐selective installation of N ϵ ‐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 N ϵ Ac sidechain into recombinantly expressed ubiquitin (Ub).