title: Effects of structural modulation on biological activity of bombesin analogues with (E)-alkene bond.
abstract: The specific bombesin receptor antagonist, (E)-alkene bombesin isostere (EABI-1), [D-Phe6,Leu13psi[(E)CH=CH]Leu14]bombesin(6-14) is a potent 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 amylase release in rat pancreatic acini. EABI-2 is a L-D diastereomer of EABI-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 100nM. On the other hand, all of four analogues had antagonist activity. The order of antagonist potency was EABI-1>EABI-3>EABI-4>EABI-2. EABI-1 was a complete antagonist, EABI-2 and EABI-3 were partial agonists, and EABI-4 had a weak agonist effect. The present study provides a useful information on the future development of peptide analogues for anticancer agents and biological tools for investigating actions of bombesin family peptides.
authors.affiliation: First Department of Surgery, Kyoto University, Sakyo-ku, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: R
authors.initials: R
authors.lastname: Doi
authors.forename: R
authors.initials: R
authors.lastname: Hosotani
authors.forename: M
authors.initials: M
authors.lastname: Wada
authors.forename: J U
authors.initials: JU
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Koshiba
authors.forename: T
authors.initials: T
authors.lastname: Ibuka
authors.forename: H
authors.initials: H
authors.lastname: Habashita
authors.forename: K
authors.initials: K
authors.lastname: Nakai
authors.forename: N
authors.initials: N
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Imamura
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D010446:Peptide Fragments; C094749:bombesin (6-14)-NH2, Phe(6)-Gln(7)-psi(CHCH)Leu(14)-; D000681:Amylases; D001839:Bombesin