Topographical requirements for delta opioid ligands: Common structural features of dermenkephalin and deltorphin

Aleksandra Misicka, Andrzej W. Lipkowski, Robert Horvath, Peg Davis, Thomas H. Kramer, Henry I. Yamamura, Victor J. Hruby

Research output: Contribution to journalArticle

76 Scopus citations


We propose a common topographical model for the bioactive conformation of deltorphin and dermenkephalin at the delta opioid receptor. In this model a hydrophilic surface from the N- to C-termini is surrounded by lipophilic residues ("hot dog" structure). The important element that orients the N-terminal tyramine is the interaction of the N-terminal amino group, with the carboxyl group of Asp4 in deltorphin I and with Asp7 through His4 (as a triad) in dermenkephalin. The biological properties of synthetic analogues designed to test this model demonstrate that the hydrophilic amino acid residues of these peptides are interchangeable. In addition, incorporation of Aib residues that change the lipophilic topography of these molecule, strongly reduces affinity for the delta opioid receptor.

Original languageEnglish (US)
Pages (from-to)1025-1032
Number of pages8
JournalLife Sciences
Issue number13
StatePublished - 1992


ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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