N-Terminally Protected Penta- and Tetrapeptide Opioid Antagonists Based on a Pentapeptide Sequence Found in the Venom of Philippine Cobra

György Orosz, András Z. Rónai, Sándor Bajusz, Kálmán Medzihradszky

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Opioid receptor antagonist properties of the μ opioid receptor selective peptide, BOC-Tyr-Lys-Lys-trp-Trp-NH2 and its systematically modified analogues were determined in guinea pig ileum, mouse vas deferens and rabbit vas deferens bioassays to locate the necessary structural features to develop κ receptor selective antagonist(s) of substantial affinity. Replacing the tyrosine residue by phenylalanine as well as increasing the lipophilicity of the C-terminal by isoamylamide substitution yielded enhanced κ receptor affinity. The presence of the C-terminal lipophilic Trp-Trp-NH2 region is necessary as revealed from the equilibrium dissociation constant values. Recognizing that only one lysine residue is required for the antagonist activity led to the synthesis of the tetrapeptide BOC-Tyr-Lys-Trp-Trp-NH2 having a κ/μ selectivity of 22 and a Ke of 5.4 μM.

Original languageEnglish
Pages (from-to)1285-1290
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume202
Issue number3
DOIs
Publication statusPublished - Aug 15 1994

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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