SYNTHESES AND BIOLOGICAL-ACTIVITIES OF BOMBESIN ANALOGS MODIFIED IN THE C-TERMINAL DIPEPTIDE PART

Bombesin receptor antagonists are possible therapeutic agents due to t heir ability to act as inhibitors of cellular proliferation. On the ba sis of our hypothesis on the mechanism of action of gastrin associatin g an activating enzyme system to the receptor and on the results repor ted in the litterature, we have synthesized bombesin analogues which h ave been modified in the C-terminal Leu(13)-Leu(14) amide part. We hav e shown that modification in the C-terminal part of the bombesin stron gly affected the biological activity in rat pancreatic acini. The most potent compound which is described here, H-D-Phe- Gln-Trp-Ala-Val-Gly -His-Leu-psi(CH2)Leu-NH2, was able to recognize the bombesin receptor on rat pancreatic acini (Ki 4.3 nM) and antagonized the bombesin stimu lated amylase secretion (Ki 7.7 nM).