Synthesis and Biological Activity of [MeTyr¹, MeArg⁷, D-Leu⁸]-Dynorphin A(1-9)-NHEt and [D-Cys²-Cys⁵, MeArg⁷, D-Leu⁸]-Dynorphin A(1-9)-NH₂

抄録

The opioid activities of [MeTyr¹]-Dyn(1-7)-NH₂, [MeTyr¹, D-Leu⁸]-Dyn(1-8)-NH₂, [MeTyr¹, D-Leu⁸]-Dyn(1-9)-NH₂, [MeTyr¹, D-Leu⁸]-Dyn(1-10)-NH₂, [MeTyr¹, D-Leu⁸]Dyn(1-11)-NH₂, and [MeTyr¹, D-Leu^{8, 12}]-Dyn(1-13)-NH₂ were examined in the bioassays (guinea pig ileum, mouse vas deferens and rabbit vas deferens). Because [MeTyr¹, D-Leu⁸]-Dyn(1-9)-NH₂ showed the most potent opioid activity of the peptides tested, the biological activities of two kinds of Dyn(1-9) analogues, [MeTyr¹, MeArg⁷, D-Leu⁸]-Dyn(1-9)-NHEt and [D-Cys²-Cys⁵, MeArg⁷, D-Leu⁸]-Dyn(1-9)-NH₂ were determined and compared with those of [MeTyr¹, MeArg⁷, D-Leu⁸]-Dyn(1-8)-NHEt and [D-Cys²-Cys⁵, MeArg⁷, D-Leu⁸]-Dyn(1-8)-NHEt in the three bioassays, in the receptor binding assays, and in the mouse tail pinch test after subcutaneous administration. The results suggest that the extension of the C-terminal in the peptide chain of [MeArg⁷, D-Leu⁸]-Dyn(1-8)-NH₂ analogues by Arg is ineffective for increasing the κ-opioid activities, κ-receptor selectivity and/or analgesic effects of the peptides.