TOTAL SYNTHESIS OF HUMAN-SECRETIN

The synthesis of the heptacosapeptide amide with the primary structure of Human-secretin is described. For this purpose 7 fragments were des igned, i.e. H-Gly-Leu-Val-NH2 [25-27b], Z-Arg(Z2)-Leu-Leu-Gln-OH [21-2 4], Z-Arg(Z2)-Leu-Gln-OH[18-20], Z-Arg(Z2)-Glu(OtBu)-Gly-Ala-OH [14-17 ], Z-Arg(Z2)-Leu-OH [12-13], Z-Thr(tBu)-Ser(tBu)-Glu(OtBu)-Leu-Ser(tBu )-OH [7-11], c-His(Adoc)-Ser(tBu)-Asp(OtBu)-Gly-Thr(tBu)-Phe-OH [1-6]; these fragments were consequently assembled to the overall protected total sequence using the Wunsch/Weygand-method with dicyclohexylcarbod iimide. After deprotection by exposure to trifluoroacetic acid in pres ence of 1,2-ethanedithiol and water as scavenger, the isolated crude p roduct was purified by column chromatography on CM-Sepharose, fast flo w. This synthetized Human-secretin showed the full biological activity in comparison to Porcine-secretin.