Native chemical ligation is a remarkable reaction that enables the chemoselective coupling of two unprotected peptides. This technology has found numerous applications in chemical biology beyond its original purpose for the synthesis of small proteins. However, there are two major limitations to its use, the requirement for a peptide thioester, not straightforward by Fmoc solid phase peptide synthesis, and the absolute requirement for an N-terminal cysteine. Recently we reported that a peptide–N-methylsulfonamide synthesised by Fmoc chemistry using the popular sulfamylbutyryl linker can participate directly in a ligation reaction with no need for prior conversion to a peptide thioester.1 We report recent developments in ligation with latent thioesters using simple Fmoc chemistry and their use in tandem with ligation auxiliaries to extend the synthetic reach of chemical ligation.
Burlina F, Morris C, Behrendt R, White P, Offer J. 2012.Simplifying native chemical ligation with an N-acylsulfonamide linker. Chem Commun; 48:2579-81