Search of the human proteome for endomorphin-1 and endomorphin-2 precursor proteins.

Search of the human proteome for endomorphin-1 and endomorphin-2 precursor proteins. Research Abstract Details 

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Search of the human proteome for endomorphin-1 and endomorphin-2 precursor proteins. Abstract Text:

Alexandra Terskiy,Kenneth M Wannemacher,Prem N Yadav,Michael Tsai,Bin Tian,Richard D Howells,Alexandra Terskiy,Kenneth M Wannemacher,Prem N Yadav,Michael Tsai,Bin Tian,Richard D Howells,Alexandra Terskiy,Kenneth M Wannemacher,Prem N Yadav,Michael Tsai,Bin Tian,Richard D Howells,

Based on the promising opioid pharmacological profile of the peptide, Tyr-Pro-Trp-Gly-NH(2) (Tyr-W-MIF), Zadina et al. [Zadina, J.E., Hackler, L., Ge, L.-J., Kastin, A.J., 1997. A potent and selective endogenous agonist for the mu-opiate receptor. Nature 386, 499-5502] synthesized and screened other Gly(4)-substituted peptides, culminating in the synthesis of Tyr-Pro-Trp-Phe-NH(2) (endomorphin-1), which displayed high affinity and selectivity for the mu-opioid receptor. The amidated peptide was then isolated from bovine brain frontal cortex, as was a related peptide, Tyr-Pro-Phe-Phe-NH(2) (endomorphin-2), that displayed similar high affinity and selectivity for the mu-opioid receptor. The biosynthesis of the endomorphins in the brain remains obscure, since the putative precursor proteins for the peptides have not been identified. With the completion of the human genome sequencing project, we hypothesized that we should uncover the biological precursors of the peptides using a bioinformatic approach to search the current human proteome for proteins that contained the endomorphin peptide sequences followed by Gly-Lys/Arg, the consensus sequence for peptide alpha-amidation and precursor cleavage. Twelve proteins were identified that contained the endomorphin-1 Tyr-Pro-Trp-Phe sequence, however none contained the Tyr-Pro-Trp-Phe-Gly sequence necessary for alpha-amidation. Twenty-two distinct proteins contained the endomorphin-2 tetrapeptide sequence, and two of those contained the sequence, Tyr-Pro-Phe-Phe-Gly, however, none contained the requisite peptide-Gly-Lys/Arg sequence. Western blot analysis using an endomorphin-2 antibody detected 4 prominent proteins in mouse brain, necessitating reinterpretation of previous immunocytolocalization studies in the brain. Screening of the current human proteome yielded no evidence for endomorphin precursor proteins based on accepted biochemical criteria.

Search of the human proteome for endomorphin-1 and endomorphin-2 precursor proteins. Publishing Authors By Initials

A Terskiy,KM Wannemacher,PN Yadav,M Tsai,B Tian,RD Howells,A Terskiy,KM Wannemacher,PN Yadav,M Tsai,B Tian,RD Howells,A Terskiy,KM Wannemacher,PN Yadav,M Tsai,B Tian,RD Howells,

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Search of the human proteome for endomorphin-1 and endomorphin-2 precursor proteins. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Life sciences

VOLUME: 81

Page Numbers: 1593-601

Journal Abbreviation: Life Sci.

ISSN: 0024-3205

DAY: 5

MONTH: 10

YEAR: 2007

Search of the human proteome for endomorphin-1 and endomorphin-2 precursor proteins. Information

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LANGUAGE: eng

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AFFILIATION: Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ, United States; Graduate School of Biomedical Science, Newark, NJ, United States.

Country: England

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MEDLINETA: Life Sci

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