Protein chemical synthesis by serine and threonine ligation

Abstract

An efficient method has been developed for the salicylaldehyde ester-mediated ligation of unprotected peptides at serine (Ser) or threonine (Thr) residues. The utility of this peptide ligation approach has been demonstrated through the convergent syntheses of two therapeutic peptides-ovine-corticoliberin and Forteo-and the human erythrocyte acylphosphatase protein (∼11 kDa). The requisite peptide salicylaldehyde ester precursor is prepared in an epi-merization-free manner via Fmoc-solid-phase peptide synthesis.