Reversible Native Chemical Ligation: A Facile Access to Dynamic Covalent Peptides Yves Ruff Valentina Garavini Nicolas Giuseppone 10.1021/ja4129845.s001 https://acs.figshare.com/articles/journal_contribution/Reversible_Native_Chemical_Ligation_A_Facile_Access_to_Dynamic_Covalent_Peptides/2302132 The broad interest of using reversible covalent bonds in chemistry, in particular at its interfaces with biology and materials science, has been recently established through numerous examples in the literature. However, the challenging exchange of peptide fragments using a dynamic covalent peptide bond has not yet been achieved without enzymatic catalysis because of its high thermodynamic stability. Here we show that peptide fragments can be exchanged by a chemoselective and reversible native chemical ligation (NCL) which can take place at <i>N</i>-(methyl)-cysteine residues. This very mild reaction is efficient in aqueous solution, is buffered at physiological pH in the presence of dithiothreitol (DTT), and shows typical half-times of equilibration in the 10 h range. 2014-04-30 00:00:00 DTT Reversible Native Chemical Ligation Dynamic Covalent PeptidesThe peptide fragments 10 h range covalent peptide bond NCL