Synthesis and biological evaluation of bombesin constrained analogues |
| |
Authors: | Cristau M Devin C Oiry C Chaloin O Amblard M Bernad N Heitz A Fehrentz J A Martinez J |
| |
Affiliation: | Laboratoire des Amino-acides, Peptides et Protéines and Centre de Biochimie Structurale, Faculté de Pharmacie, UMR 5810, CNRS-Universités Montpellier I & II, 15 avenue Charles Flahault, 34060 Montpellier, Cédex 2, France. |
| |
Abstract: | Analogues of bombesin which incorporate dipeptide or turn mimetics have been synthesized. One of them (compound 11) containing a seven-membered lactam ring revealed a good affinity for GRP/BN receptors on rat pancreatic acini (K(i) value of 1.7 +/- 0.4 nM) and on Swiss 3T3 cells (K(i) value of 1.0 +/- 0.2 nM). On the basis of this observation, antagonists containing the same dipeptide mimic were obtained by modification of the C-terminal part of the bombesin analogues. The most potent constrained compounds (15 and 17) were able to antagonize 1 nM bombesin-stimulated amylase secretion from rat pancreatic acini with high potency (K(i) = 21 +/- 3 and 3.3 +/- 1.0 nM, respectively) and 10(-7) M bombesin-stimulated ?(3)Hthymidine incorporation into Swiss 3T3 cells (K(i) = 7.8 +/- 2. 0 and 0.5 +/- 0.1 nM, respectively). |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|