ja4129845_si_001.pdf (12.52 MB)
Reversible Native Chemical Ligation: A Facile Access to Dynamic Covalent Peptides
journal contribution
posted on 2014-04-30, 00:00 authored by Yves Ruff, Valentina Garavini, Nicolas GiusepponeThe
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 N-(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.