New publication

09 April 2014

Reversible Native Chemical Ligation: A Facile Access to Dynamic Covalent Peptides

With a hydrolysis half-time of several years in neutral water the peptide bond is one of the most stable in biological systems. It is responsible of the structure and functions of proteins, and therefore self-assembled and adaptive chemical systems based on peptide structures are of high interest.

Despite this great potential, only a few groups have described the use of proteases or sortase to catalyze covalent exchange reaction at the peptide junction under mild conditions. In addition the scope of these methods is limited by the intrinsic sequence specificity and stability of these enzymes and therefore alternative approaches are desirable.

We recently hijacked the most popular ligation reaction in peptide chemistry, namely the native chemical ligation, to allow exchange reaction under physiological conditions between peptide fragments only composed of natural amino acids, without any additional enzymatic catalysis. This novel methodology has a tremendous potential in the dynamic combinatorial chemistry of peptides and opens the door to the preparation of native adaptive peptides or proteins through covalent exchange of functional peptide domains.

We are currently working on applying our reversible native chemical ligation methodology for the preparation of novel bioactive peptides with adaptive properties, and on the extension of our methodology to other peptide or amide bonds that are relevant for the development of (bio)materials.

Reversible Native Chemical Ligation: A Facile Access to Dynamic Covalent Peptides

Ruff, Y. ; Garavini, V. ; Giuseppone, N.
J. Am. Chem. Soc.
2014, 136, 6333–6339
Highighted in: Nature SciBX, 2014, 7