ACYL DISULFIDE-MEDIATED INTRAMOLECULAR ACYLATION FOR ORTHOGONAL COUPLING BETWEEN UNPROTECTED PEPTIDE SEGMENTS - MECHANISM AND APPLICATION

A highly efficient orthogonal coupling approach for peptide bond forma tion using unprotected peptide segments was described. The key element of this approach consisted of capturing an Npys modified N-Cys side-c hain thiol of the amino segment with a C-alpha-thiocarboxylic acid of the acyl segment to form an acyl disulfide which undergoes rapid intra molecular acylation to generate an amide bond. A final product with a native Cys residue at the ligation site Was obtained after a thiolytic reduction step.