Beschreibung:
<jats:p>The properties of di‐ and tri‐peptides containing 1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid (Tic) in second position suggest that the message domain of opioid peptides can be composed of only two residues [Temussi, P. A., Salvadori, S., Amodeo, P., Guerrini, R., Tomatis, R., Lazarus, L. H., Picone, D. & Tancredi, T. (1994) <jats:italic>Biochem. Biophys. Res. Commun. 198</jats:italic>, 933–9391. As a crucial test of the possibility that the Tyr‐Tic segment be a message domain in longer peptide sequences, we have inserted it in the sequences of two typical opioid peptides: [Leu]enkephalin, a non‐selective agonist, and dermorphin, a selective μ agonist. Here we report the synthesis and biological activity of [<jats:sc>l</jats:sc>‐Tic<jats:sup>2</jats:sup>]enkephalin, [<jats:sc>l</jats:sc>‐Tic<jats:sup>2</jats:sup>]dermorphin, [<jats:sc>l</jats:sc>‐Tic<jats:sup>2</jats:sup>]dermorphin carboxylic acid and [<jats:sc>d</jats:sc>‐Tic<jats:sup>2</jats:sup>]dermorphin: all [<jats:sc>l</jats:sc>‐Tic<jats:sup>2</jats:sup>]peptides were converted from agonists to δ‐selective antagonists. The NMR conformational study in a dimethylsulfoxide/water cryoprotective mixture at low temperature shows diagnostic side‐chainside‐chain NOEs in the spectra of all [<jats:sc>l</jats:sc>‐Tic<jats:sup>2</jats:sup>]peptides and hints that the 90° arrangement of the the two aromatic rings found in the cis‐Tyr‐<jats:sc>l</jats:sc>‐Tic moiety, typical of <jats:italic>N</jats:italic> ‐methyl naltrindole and other δ‐selective opiate antagonists, is responsible for the antagonist activity of all these peptides.</jats:p>