On-resin synthesis of the somatostatin venom analog Consomatin Ro1

Abstract

Consomatin Ro1 is a disulfide-containing peptide derived from the venom of the cone snail Conus rolani with a sequence that is similar to the vertebrate peptide hormone somatostatin. It has been shown to preferentially activate human somatostatin receptor subtypes 1 and 4, and to exhibit antinociceptive and antihyperalgesic properties making it an interesting peptide to study and develop as a chemical probe or an analgesic drug. Here, we describe the synthesis of Consomatin Ro1 using an onresin approach wherein the disulfide bond is formed while the peptide is still attached to the resin. This was achieved by selectively removing the methoxytrityl protecting group of Cys residues with a weak acidic mixture, and treating the resulting thiol-containing peptidyl resin with the mild oxidant Nchlorosuccinimide. The strategy yielded a considerably higher amount of the peptide when compared with the previously reported in-solution disulfide formation method.