Synthesis and evaluation of potential affinity labels derived from endomorphin-2

H. Choi, Thomas F. Murray, Jane V. Aldrich

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In an attempt to identify potential peptide-based affinity labels for opioid receptors, endomorphin-2 (Tyr-Pro-Phe-PheNH2), a potent and selective endogenous ligand for μ-opioid receptors, was chosen as the parent peptide for modification. The tetrapeptide analogs were prepared using standard Fmoc-solid phase peptide synthesis in conjunction with incorporation of Fmoc-Phe(p-NHAIIoc) and modification of the p-amino group. The electrophilic groups isothiocyanate and bromoacetamide were introduced into the para position on either Phe3 or Phe4; the corresponding free amine-containing peptides were also prepared for comparison. The peptides bearing an affinity label group and their free amine analogs were evaluated in a radioligand-binding assay using Chinese hamster ovary (CHO) cells expressing μ- and δ-opioid receptors. Modification on Phe4 was better tolerated than on Phe3 for μ-receptor binding. Among the analogs tested, [Phe(p-NH2)4]endomorphin-2 showed the highest affinity (IC50 = 37 nM) for μ-receptors. The Phe(p-NHCOCH2Br)4 analog displayed the highest μ-receptor affinity (IC50 = 158 nM) among the peptides containing an affinity label group. Most of the compounds exhibited negligible binding affinity for δ-receptors, similar to the parent peptide.

Original languageEnglish
Pages (from-to)58-62
Number of pages5
JournalJournal of Peptide Research
Volume61
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

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Affinity Labels
Peptides
Opioid Receptors
Inhibitory Concentration 50
Amines
Bearings (structural)
Radioligand Assay
Solid-Phase Synthesis Techniques
Cricetulus
endomorphin 2
Ovary
Assays
Ligands
Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology

Cite this

Synthesis and evaluation of potential affinity labels derived from endomorphin-2. / Choi, H.; Murray, Thomas F.; Aldrich, Jane V.

In: Journal of Peptide Research, Vol. 61, No. 2, 01.02.2003, p. 58-62.

Research output: Contribution to journalArticle

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