Cleavable Cys labeling directed Lys site-selective stapling and single-site modification

Site-selective modification of peptide/protein is a vital approach to disclose post-translational modifications(PTMs) and plays a crucial role in chemical biology, as well as drug development. Compared with synthetic and chemical biology methods, chemical modification of native peptide/protein provides a more versatile approach to achieve late-stage diversification for functional studies. Lysine featured high nucleophilicity, frequency, and solvent accessibility, making its site-selective modification important but elusive. Herein, we reported a visible-light-driven and Cys-directed Lys site-selective stapling approach for peptide/protein. By cleavable Cys anchoring, site-selective Lys single-site modification was achieved, and this method could be applied to multi-functionalization.