SEA Native Peptide Ligation

The most frequently used technique for synthesizing proteins is Native chemical ligation (NCL).

This reaction proceeds probably through the formation of a transient thioester intermediate, obtained by intramolecular attack of one SEA thiol on the peptide C-terminal carbonyl group as shown in Scheme 1.

Then, the thioester undergoes a series of thiol-thioester exchanges, including with exogeneous thiols present in the ligation mixture such as mercaptophenyl acetic acid (MPAA).

Exchange with the cysteine thiol group of the second peptide segment results in a transient thioester intermediate, which as for Native Chemical Ligation, rearranges by intramolecular S,N-acyl shift migration into a native peptide bond.

The first peer reviewed publication describing SEA native peptide ligation was published in Organic Letters by Melnyk, O. et al. (Ollivier, N.; Dheur, J.; Mhidia, R.; Blanpain, A.; Melnyk, O., Bis(2-sulfanylethyl)amino native peptide ligation.