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Bioactivity studies on atypical natural opioid hexapeptides processed from proenkephalin (PENK) precursor polypeptides

Bojnik, Engin and Kleczkowska, P. and de Velasco, E. M. F. and Corbani, M. and Babos, F. and Benyhe, Sándor (2014) Bioactivity studies on atypical natural opioid hexapeptides processed from proenkephalin (PENK) precursor polypeptides. Comparative Biochemistry and Physiology - Part B: Biochemistry and Molecular Biology, 174. pp. 29-35. ISSN 1096-4959

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Abstract

Endogenous opioids are derived from four related polypeptide precursors: proenkephalin (PENK), prodynorphin (PDYN), pronociceptin (PNOC) and proopiomelanocortin (POMC). In mammals PENK encodes for four copy of Met-enkephalin, one octapeptide Met-enkephalin-Arg-Gly-Leu, one heptapeptide Met-enkephalin-Arg-Phe and a single copy of Leu-enkephalin. Our detailed bioinformatic search on the existing PENK sequences revealed several atypical hexapeptide Met-enkephalins in different vertebrate animals. They are located either in the second enkephalin unit or in the seventh enkephalin core position at the C-terminus. Altogether four different hexapeptide sequences were obtained representing eleven animal species: Met-enkephalin-Arg(6) (YGGFMR) in the bird zebra finch, Met-enkephalin-Asp(6) (YGGFMD), Met-enkephalin-IIe(6) (YGGFMI) in zebrafish; and Met-enkephalin-Ser(6) (YGGFMS) in two pufferfish species. All novel peptides were chemically synthesized and studied in receptor binding and G-protein activation assays performed on rat brain membranes. The four novel enkephalins were equipotent in stimulating G-proteins. Affinities of the peptides determined by equilibrium competition assays in teceptor binding experiments were statistically different. At the MOP receptors the highest affinity (K-i 4 nM) was obtained with the zebra finch peptide Met-enkephalin-Arg6. The pufferfish Met-enkephalin-Ser6 exhibited the highest affinity (K-i 6.7 nM) at the DOP receptor. 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 concept is expected. (C) 2014 Elsevier Inc All rights reserved.

Item Type: Article
Subjects: Q Science / természettudomány > Q1 Science (General) / természettudomány általában
Q Science / természettudomány > QR Microbiology / mikrobiológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 18 Oct 2014 07:38
Last Modified: 18 Oct 2014 07:38
URI: http://real.mtak.hu/id/eprint/17745

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