Structure-activity relationships of gastrointestinal hormones: motilin, GIP, and [27-TYR]CCK-PZ

The docosapeptide and the tritetracontapeptide corresponding to the entire amino acid sequence of porcine motilin and gastric inhibitory peptide were synthesized, and in addition, an unsulfated form of cholecystokinin-pancreozymin (CCK-PZ) was prepared to cast some light on the structure-activity relationships of these gastrointestinal hormones. In a series of motilin peptides, elimination of the pentapeptide from the amino terminus decreased the activity (in vitro contraction of rabbit duodenal muscle) to 1/250 of the whole molecule, and subsequent removal of the tripeptide Thr-Tyr-Gly resulted in the complete loss of its effects, In a series of gastric inhibitory peptides, two fragments corresponding to positions 1 to 28 and 26 to 43 were both inactive. However, the nonacosapeptide (15 to 43) retained one-fourth of the activity of the tritetracontapeptide (suppression of the gastric acid secretion stimulated by tetragastrin in Heidenhain pouch dogs). Synthetic [27-Tyr]CCK-PZ exhibited 1/250 of the activity of natural CCK-PZ (amylase release from rat pancreas). This compound was smoothly and efficiently labeled with 125I (specific activity 200 to 250 muc per mug).