Reversible native chemical ligation: a facile access to dynamic covalent peptides.
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 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.
SAMS Research Group, University of Strasbourg, Institut Charles Sadron, CNRS, 23 rue du Loess, BP 84047, 67034 Strasbourg Cedex 2, France.
Yves
Y
Ruff
Valentina
V
Garavini
Nicolas
N
Giuseppone
D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D004226:Dithioerythritol / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D013816:Thermodynamics
D010455:Peptides; D004226:Dithioerythritol; D003545:Cysteine; C017507:mecysteine