Development of Powerful Auxiliary-Mediated Ligation To Facilitate Rapid Protein Assembly

Here, we describe an Se-auxiliary mediated ligation protocol capable of rapid native chemical ligations at sterically hindered junctions, followed by in situ auxiliary cleavage under neutral conditions without affecting unprotected Cys residues. This auxiliary, which is prepared from phenyl acetaldehyde in one step, can be conveniently attached to the N-terminal region of a peptide via a reductive amination or coupling reaction. We demonstrated this methodology by synthesizing two protein samples.