Synthesis and binding characteristics of a novel enkephalin analogue, [3H]Tyr-D-Ala-Gly-Phe-D-Nle-Arg-Phe
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Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides
Published on: August 20, 2018
Fanni Tóth1, Judit Farkas, Géza Tóth
1Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, P.O. Box 521, Szeged H-6701, Hungary.
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 micro-receptor selectivity, and hydrophobicity of the peptide all contribute to the effectiveness observed in biochemical and pharmacological studies.
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