Bioinformatic and biochemical studies on the phylogenetic variability of proenkephalin-derived octapeptides

E. Bojnik, F. Babos, A. Magyar, A. Borsodi, S. Benyhe

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Leu- and Met-enkephalins are proenkephalin-derived endogenous pentapeptides with opioid (morphine) activity. Among the seven enkephalin units found in the human proenkephalin (PENK), the fourth copy being an octapeptide: Tyr-Gly-Gly-Phe-Met-Arg-Gly-Leu (HsYGGFMRGL). Bioinformatic analysis of the available PENK sequences revealed the presence of other octapeptide orthologues in these precursor polypeptides. Four types of the elongated Met-enkephalins we identified by searching protein databases, XlYGGFMRGY (three frog species and platypus), GgYGGFMRSV (chicken and one fish species), HpYGGFMNGF (shark) and MmYGGFMRSL (mouse and two lungfish species) were chemically synthesized and studied in receptor binding and G-protein activation assays performed on rat brain membranes. All peptides have also been prepared containing oxidized methionine (M(O)). The overall binding and signalling profile of the novel octapeptides revealed moderate opioid agonist activities and a rank order of potencies for the mu∼delta≫kappa receptor binding sites. Peptides with the oxidized M(O) residue were found to be less potent in both receptor binding and G-protein stimulation studies. Phylogenetic neuropeptide libraries, defined here as a collection of mutationally different species variants of orthologous and paralogous peptide sequences, represent the natural molecular diversity of the neuropeptides. Such libraries can provide a wide range of structural information establishing comparative functional analyses. Since DNA sequencing data are rapidly increasing, more development in the natural peptide library approach is expected.

Original languageEnglish
Pages (from-to)542-552
Number of pages11
JournalNeuroscience
Volume165
Issue number2
DOIs
Publication statusPublished - Jan 20 2010

Fingerprint

Computational Biology
Methionine Enkephalin
Peptides
Arg(6)-Gly(7)-Leu(8)-enkephalin-met
Neuropeptides
GTP-Binding Proteins
Methionine
Opioid Analgesics
Carrier Proteins
Platypus
Leucine Enkephalin
Sharks
Peptide Library
Protein Databases
Enkephalins
DNA Sequence Analysis
Anura
Morphine
Libraries
Chickens

Keywords

  • binding assay
  • chemical biodiversity
  • enkephalin
  • opioid receptor
  • PENK evolution
  • phylogenetic neuropeptide library

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bioinformatic and biochemical studies on the phylogenetic variability of proenkephalin-derived octapeptides. / Bojnik, E.; Babos, F.; Magyar, A.; Borsodi, A.; Benyhe, S.

In: Neuroscience, Vol. 165, No. 2, 20.01.2010, p. 542-552.

Research output: Contribution to journalArticle

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