EFFECTS OF STRUCTURAL MODULATION ON BIOLOGICAL-ACTIVITY OF BOMBESIN ANALOGS WITH (E)-ALKENE BOND

The specific bombesin receptor antagonist, (E)-alkene bombesin isoster e (EABI-1), -Phe(6),Leu(13)Psi[(E)CH=CH]Leu(14)]bombesin(6-14) is a po tent antagonist in terms of inhibition of bombesin-stimulated amylase release from rat pancreatic acini. This study examined the effects of EABI-1 (L-L diastereomer) and three novel bombesin analogues on amylas e release in rat pancreatic acini. EAB1-2 is a L-D diastereomer of EAB I-1. EABI-3 is an analogue, of which leucine at position 13 of EABI-1 was replaced with valine. EABI-4 is a L-D diastereomer of EABI-3 (L-L) . The order of agonist potency was EABI-2>EABI-3>EABI-4. EABI-1 showed no agonist activity at concentrations up to 100 nM. On the other hand , all of four analogues had antagonist activity. The order of antagoni st potency was EABI-1>EABI-3>EABI-4>EABI-2. EABI-1 was a complete anta gonist, EAB1-2 and EABI-3 were partial agonists, and EABI-4 had a weak agonist effect. The present study provides a useful information on th e future development of peptide analogues for anticancer agents and bi ological tools for investigating actions of bombesin family peptides.