Synthesis and binding characteristics of a novel enkephalin analogue, [3H]Tyr-D-Ala-Gly-Phe-D-Nle-Arg-Phe

Fanni Tóth, Judit Farkas, Géza Tóth, Mária Wollemann, Anna Borsodi, Sándor Benyhe

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The endogenous opioid heptapeptide (Tyr-Gly-Gly-Phe-Met-Arg-Phe; MERF) has been shown to interact with multiple opioid as well as non-opioid sites in mammalian brain membranes. To increase the stability and bioavailability of MERF, new synthetic derivatives with D-amino acid substitutions were prepared and studied. One of the new compounds in this series, Tyr-D-Ala-Gly-Phe-D-Nle- Arg-Phe (DADN), had only moderate affinity in competing with [ 3H]MERF, whereas it displayed the highest potency in producing antinociception following intrathecal administration. DADN was radiolabeled with 41Ci/mmol specific activity. Specific binding of [3H]DADN was saturable, stereoselective and of high affinity. Chemical stability, increased μ-receptor selectivity, and hydrophobicity of the peptide all contribute to the effectiveness observed in biochemical and pharmacological studies.

Original languageEnglish
Pages (from-to)1433-1440
Number of pages8
JournalPeptides
Volume24
Issue number9
DOIs
Publication statusPublished - Sep 2003

Keywords

  • Ligand binding
  • Met-enkephalin-Arg-Phe
  • Opioid receptors
  • Radiolabeling
  • Rat brain

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Synthesis and binding characteristics of a novel enkephalin analogue, [<sup>3</sup>H]Tyr-D-Ala-Gly-Phe-D-Nle-Arg-Phe'. Together they form a unique fingerprint.

  • Cite this