Biological effects and receptor binding affinities of new pseudononapeptide bombesin/GRP receptor antagonists with N-terminal D-Trp or D-Tpi.
作者： SINISA RADULOVIC , REN-ZHI CAI , PETER SERFOZO , KATE GROOT , TOMMIE W. REDDING
DOI: 10.1111/J.1399-3011.1991.TB01545.X
关键词:
摘要: In an attempt to produce more powerful (effective) bombesin/GRP receptor antagonists, the D forms of Trp or analog (Tpi) were introduced at position 6 in two pseudononapeptides, Leu13 psi (CH2NH)Leu14-bombesin(6-14) and psi(CH2NH)Phe14-bombesin (6-14). These antagonists tested for their ability inhibit basal gastrin releasing peptide (GRP) (14-27)-induced amylase release from rat pancreatic acini a superfusion assay. They also assessed inhibition 125I-Tyr4-bombesin binding Swiss 3T3 small cell lung carcinoma line H-345 mitogenic response cells induced by GRP(14-27). The peptides, when given alone, did not stimulate secretion, but able release. All showed strong affinities suppressed GRP(14-27)-induced increase [3H]thymidine incorporation into DNA nanomolar concentrations. Antagonist D-Tpi6,Leu13 (CH2NH)Leu14-bombesin (6-14)(RC-3095) was slightly potent these assays than D-Trp6,Leu13 (6-14)(RC-3125). Nevertheless, (CH2NH)Phe14-bombesin (6-14) highest affinity H345 it most inhibitor secretion. This antagonist RC-3420 particularly effective inhibiting growth cells, exhibiting IC50 value less 1 nM.(ABSTRACT TRUNCATED AT 250 WORDS)
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