Synthesis of reaper protein by a thioester method using silver chloride as an activator

Abstract

In the previous papers, we described polypeptide syntheses using a thioester method, in which peptide thioesters are used as building blocks [1]. A peptide thioester, which contained a Cys(Acm) residue, was successfully condensed in the presence of silver nitrate and 3,4-dihydro-3-hydroxy-4-oxo-1,2,3benzotriazine (HOObt) in the synthesis of adrenomedullin [2]. Loss of the Acm groups during segment condensation was not observed in this synthesis. However, the undesirable removal of an Acm group was observed in the synthesis of reaper protein, which contains 65 amino acid residues including one Cys residue [3]. In order to overcome the problem, we searched the conditions under which an Acm group is stable and the condensation reactions proceed at an acceptable rate using model peptide thioesters [4]. In this paper, we describe the effect of silver salts and the synthesis of reaper protein.