Studies on Peptides. CLX. : Synthesis of a 33-Residue Peptide Corresponding to the Entire Amino Acid Sequence of Human Cholecystokinin (hCCK-33)

Abstract

An unsulfated form of human cholecystokinin (hCCK-33) was synthesized by successive azide condensations of seven peptide fragments, followed by deprotection with 1 M trimethylsilyl trifluoromethanesulfonate/trifluoroacetic acid. The phenolic group of Tyr (position 27) was selectively sulfated with pyridine-SO₃ complex, after reversible masking of other functional groups with hard base (F^-)-labile protecting groups, i.e., the amino functions with 9-fluorenyl-methyloxycarbonyl group and the hydroxyl functions of 4 Ser residues with tert-butyldiphenylsilyl groups. In terms of pancreatic protein output and capillary blood flow in dogs, the relative potency of synthetic hCCK-33 with respect to that of synthetic CCK-8 (taken as 1 on a molar basis) was 0.9. In terms of gastric acid and pepsin output in rat in vivo assays, synthetic hCCK-33 was about 2- to 3-fold more potent than CCK-8 on a molar basis.