A new method of N to C sequential ligation using thioacid capture ligation and native chemical ligation.

Sequential peptide ligation strategy becomes more and more important in large protein or long peptides chemical synthesis due to the limited peptide/protein size obtained by solid phase synthesis of individual peptides or even one-step peptide ligation. Herein, we developed an alternative method which could perform the sequential peptide ligation of several segments from N to C direction based on the combined use of thioacid capture ligation and native chemical ligation. The sweet protein monellin was produced through this strategy on a scale of multi-milligrams.