Sequential native chemical ligation utilizing peptide thioacids derived from newly developed Fmoc-based synthetic method

The first facile Fmoc-based synthetic procedure for peptide thioacids was developed. Successful application of the resulting thioacids to sequential native chemical ligation (NCL) in the N to C direction was achieved. Conversion of the peptide thioacids to the corresponding thioesters with Ellmanʹs reagent followed by NCL in the presence of tris(2-carboxyethyl)phosphine (TCEP) and thiophenol was accomplished in a one-pot manner.