Side chain modifications change the binding and agonist properties of endomorphin 2

I. Lengyel, D. Biyashev, C. Tömböly, G. Tóth, A. Borsodi, G. Orosz, L. Kocsis, M. Al-Khrasani, A. Rónai, Z. Fürst

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Abstract

Side chain modifications were introduced to endomorphin 2 (E2) to improve its binding properties and biological activity. A number of C-terminal modifications decreased the binding affinity to the mu-opioid receptor and the intrinsic activity in rat brain membranes. The exception was E2-ol, which showed increased binding affinity to MOR and higher potency in stimulating [35S]GTPγS binding. N-methylation of Phe3 (MePhe3) attenuated the binding affinity and produced a rightward shift of [35S]GTPγS binding curves. All derivatives had lower intrinsic activity than E2. Some of the modified peptides partially inhibited, while YPF-benzyl-allyl-amide fully inhibited, the E2 or [D-Ala2, MePhe4, Gly5ol]enkephalin stimulated [35S]-GTPγS binding. Marked differences were found between the results obtained using tritiated E2, tritiated naloxone, and [35S]GTPγS binding, indicating the possible involvement of multiple binding sites. The data presented demonstrate that the C-terminal amide group has an essential role in the regulation of the binding and the agonist/antagonist properties of E2.

Original languageEnglish
Pages (from-to)153-161
Number of pages9
JournalBiochemical and biophysical research communications
Volume290
Issue number1
DOIs
Publication statusPublished - jan. 1 2002

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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