Conformationally constrained deltorphin analogs with 2-aminotetralin-2- carboxylic acid in position 3

Géza Tóth, Zsuzsa Darula, Antal Péter, Ferenc Fülöp, Dirk Tourwé, Hendrika Jaspers, Patricia Verheyden, Zsolt Böcskey, Zoltán Tóth, Anna Borsodi

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34 Citations (Scopus)


Two approaches to the design of very active and highly selective δ opioid peptides were used to obtain new deltorphin analogs with altered hydrophobic and stereoelectronic properties. Deltorphin I and II analogs were synthesized involving the substitution of Ile instead of Val at positions 5 and 6 in the address domain and 2-aminotetralin-2-carboxylic acid (Atc) instead of Phe in the message domain. The peptides were agonists in the subnanomolar range in the MVD assay and in the micromolar or higher range in the GPI assay, showing a very high selectivity for δ receptors. A very similar trend could be observed in radioreceptor binding assays in which selective tritiated opioid ligands were used. (R)- and (S)-Atc-deltorphins exhibited similar K(i) values in the binding assay, with almost complete loss of the stereospecificity of the binding. Conformational studies provided evidence for little disturbance of the backbone conformational equilibrium when Phe3 is replaced by (S)- or (R)-Atc. The use of the Atc constraint gives additional evidence that, during its interaction with the δ receptor, the side chain of residue 3 adopts the trans conformation at χ1.

Original languageEnglish
Pages (from-to)990-995
Number of pages6
JournalJournal of Medicinal Chemistry
Issue number6
Publication statusPublished - Mar 14 1997

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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