Isopeptide method: development of S-acyl isopeptide method for the synthesis of difficult sequence-containing peptides

A novel strategy for a more efficient synthesis of difficult sequence-containing peptides, the S-acyl isopeptide method, was developed and successfully applied. A model pentapeptide Ae-Val-Val-Cys-Val-Val-NH2 was synthesized via its water-soluble S-acyl isopeptide using art S-acyl isodipeptide unit, Boc-Cys(Fmoc-Val)-OH. An S-acyl isopeptide possessing excellent water solubility could be readily and quantitatively converted to the native peptide via an S-N intramolecular acyl migration reaction at pH 7.4. Thus, the S-acyl isopeptide method provides a useful tool in peptide chemistry. Copyright (C) 2008 European Peptide Society and John Wiley & Sons. Ltd.