Studies on Peptides. XXVII. Synthesis of the Decapeptide, ACTH-(5-14), as an Example of Peptide-Fragment Condensation on the Polymer Support

As an example of peptide fragment condensation on the polymer support, synthesis of the tryptophan-containing decapeptide, ACTH-(5-14) was undertaken. First, suitable conditions to esterify Boc-Lys (Z)-Pro-Val-Gly-OH onto the copolymer of styrene and 2% divinylbenzene were examined. At room temperature, fairly good esterification of this tetrapeptide was achieved by the use of the bromomethylated copolymer and dicyclohexylamine. The peptide-resin was then treated with 1N HCl and triethylamine. To the resulting free tetrapeptide-resin, Z-Glu (OBzl)-His-Phe-Arg (NO2)-Trp-Gly-OH was condensed by means of DCC and the growing peptide resin was treated with HF. The product, H-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-Gly-OH was obtained simply by column chromatography on CM-cellulose.