Synthesis of an O-acyl isopeptide by using native chemical ligation to efficiently construct a hydrophobic polypeptide

Abstract By using dimethylformamide to suppress the O -to- N acyl migration, we efficiently synthesized an O -acyl isopeptide by native chemical ligation of a peptide-thioester and a Cys- O -acyl isopeptide. The reaction mixture was then loaded onto an octadecylsilane reverse-phase HPLC column, and the isopeptide was purified by using a linear gradient of CH 3 CN in 0.1% aqueous trifluoroacetic acid. The recovery rate of the O -acyl isopeptide was considerably higher than that of the corresponding native polypeptide. Synthesis of O -acyl isopeptides via native chemical ligation, with O -to- N acyl migration as the final step to give the native form, has potential as an efficient method of constructing hydrophobic polypeptides.