Synthesis of Cysteine-Containing Polypeptide Using a Peptide Thioester Containing a Cys(Acm) Residue

Abstract

Abstract A method was developed for the preparation of a cysteine-containing polypeptide, using a Cys(Acm)-containing peptide thioester obtained by a Boc solid-phase method. To demonstrate the utility of the developed method, human adrenomedullin consisting of 52 amino acid residues was synthesized. A peptide thioester, Boc–[Cys(Acm)16]–adrenomedullin(1—19)-SCH2CH2CO-β-Ala–NH2, and [Cys(Acm)21, Lys(Boc)25,36,38,46]-adrenomedullin(20—52) were prepared by conventional solid-phase methods. These peptide segments were condensed in the presence of silver ions, an additive, and a base. When HOBt or HOOBt was used as an additive, the segment coupling proceeded with negligible decomposition of Acm groups to give the desired product. A method for the removal of S-Acm groups from cysteine residues under basic conditions in the presence of silver ions and water, is also described.