Penta- and tetrapeptides related to met-enkephalin modified in position 2 and at the C-terminus, and β-endorphin derivatives, modified in position 5, were studied. The biological activities were determined in vitro, in electrically stimulated longitudinal muscle strip of guinea-pig ileum (GPI) and mouse vas deferens (MVD) preparations and in vivo, in the rat tail flick test. The α-helix potential of endorphin derivatives and the molar ellipticity values for enkephalin analogues were calculated from circular dichroism spectra. The opioid receptors in GPI preferred ligands with high capacity to exist in folded form whilst for the receptors in MVD the character of the C-terminal part of enkephalin analogues seemed to be the primary determinant. The latter receptor type accepted flexible ligands even more readily than rigid ones. Studies with enkephalin analogues bearing sulfonic or phosphonic acid in position 5 revealed that the enkephalin-like property in a pentapeptide (high MVD) GPI potency ratio, the poor antagonizability by naltrexone in MVD given intravenously or intracerebroventricularly works against the analgesic potency, even if the peptide is enzyme-protected.
|Issue number||SUPPL. 5|
|Publication status||Published - Jan 1 1980|
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