Synthesis of cysteine-containing polypeptide using a peptide thioester containing a Cys(Acm) residue

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-beta-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.