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

Area of Science:

• Endocrinology
• Gastroenterology
• Peptide Chemistry

Background:

• Gastrointestinal hormones regulate digestive functions.
• Understanding structure-activity relationships is crucial for drug development.

Purpose of the Study:

• Synthesize porcine motilin, gastric inhibitory peptide (GIP), and unsulfated cholecystokinin-pancreozymin (CCK-PZ).
• Investigate the structure-activity relationships of these gastrointestinal hormones.

Main Methods:

• Chemical synthesis of docosapeptide and tritetracontapeptide analogs of motilin and GIP.
• Preparation of unsulfated CCK-PZ.
• In vitro assays for muscle contraction and in vivo assays for gastric acid secretion.
• Radiolabeling of synthetic CCK-PZ with 125I.

Main Results:

• Truncation of motilin from the N-terminus significantly reduced its muscle contractile activity.
• A GIP fragment (15-43) retained 25% of the activity in suppressing gastric acid secretion.
• Synthetic [27-Tyr]CCK-PZ showed 1/250 activity and was successfully labeled with 125I.

Conclusions:

• Specific amino acid sequences are critical for the biological activity of motilin and GIP.
• Structure-activity studies provide insights into the function of these gastrointestinal hormones.
• Synthetic peptide analogs can be valuable tools for further research and potential therapeutic applications.