Abstract
In naturally occurring protein splicing, cystein thiol-assisted cleavage of the peptide bond adjacent to the Cys residue is the initial step of the reaction affording peptide thioester via N-S acyl transfer, where loss of planarity of the amide bond has been reported to be responsible for the activation of the peptide bond. On the basis of protein splicing mechanism, we attempted to develop the biomimetic methodology for the preparation of peptide thioesters which have shown their great potential in the peptide/protein synthesis utilizing native chemical ligation (NCL) protocols. We evaluated the system utilizing an S-protected cysteine-derived N-acyloxazolidinone to activate amide bond resulting in the formation of peptide thioesters. In this system, removal of S-protection can trigger the acyl transfer from the activated amide bond to the deprotected thiol group. And this newly developed biomimetic protocol for thioesters was successfully applied to the synthesis of 32-mer peptide (hBNP derivative) using NCL.
