Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
RNA
2004 Mar 01;103:516-27. doi: 10.1261/rna.5186504.
Show Gene links
Show Anatomy links
Biostable aptamers with antagonistic properties to the neuropeptide nociceptin/orphanin FQ.
Faulhammer D
,
Eschgfäller B
,
Stark S
,
Burgstaller P
,
Englberger W
,
Erfurth J
,
Kleinjung F
,
Rupp J
,
Dan Vulcu S
,
Schröder W
,
Vonhoff S
,
Nawrath H
,
Gillen C
,
Klussmann S
.
???displayArticle.abstract???
The neuropeptide nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor, has been shown to play a prominent role in the regulation of several biological functions such as pain and stress. Here we describe the isolation and characterization of N/OFQ binding biostable RNA aptamers (Spiegelmers) using a mirror-image in vitro selection approach. Spiegelmers are L-enantiomeric oligonucleotide ligands that display high affinity and specificity to their targets and high resistance to enzymatic degradation compared to D-oligonucleotides. A representative Spiegelmer from the selections performed was size-minimized to two distinct sequences capable of high affinity binding to N/OFQ. The Spiegelmers were shown to antagonize binding of N/OFQ to the ORL1 receptor in a binding-competition assay. The calculated IC(50) values for the Spiegelmers NOX 2149 and NOX 2137a/b were 110 nM and 330 nM, respectively. The competitive antagonistic properties of these Spiegelmers were further demonstrated by their effective and specific inhibition of G-protein activation in two additional models. The Spiegelmers antagonized the N/OFQ-induced GTPgammaS incorporation into cell membranes of a CHO-K1 cell line expressing the human ORL1 receptor. In oocytes from Xenopus laevis, NOX 2149 showed an antagonistic effect to the N/OFQ-ORL 1 receptor system that was functionally coupled with G-protein-regulated inwardly rectifying K(+) channels.
Antao,
A thermodynamic study of unusually stable RNA and DNA hairpins.
1991, Pubmed
Antao,
A thermodynamic study of unusually stable RNA and DNA hairpins.
1991,
Pubmed
Bloms-Funke,
Agonistic effects of the opioid buprenorphine on the nociceptin/OFQ receptor.
2000,
Pubmed
,
Xenbase
Brody,
Aptamers as therapeutic and diagnostic agents.
2000,
Pubmed
Burnside,
Species differences in the efficacy of compounds at the nociceptin receptor (ORL1).
2000,
Pubmed
Calo',
Characterization of [Nphe(1)]nociceptin(1-13)NH(2), a new selective nociceptin receptor antagonist.
2000,
Pubmed
Calo',
Pharmacology of nociceptin and its receptor: a novel therapeutic target.
2000,
Pubmed
Calo',
Pharmacological profile of nociceptin/orphanin FQ receptors.
2002,
Pubmed
Calo',
Nociceptin/orphanin FQ receptor ligands.
2000,
Pubmed
Convery,
Crystal structure of an RNA aptamer-protein complex at 2.8 A resolution.
1998,
Pubmed
Darland,
Orphanin FQ/nociceptin: a role in pain and analgesia, but so much more.
1998,
Pubmed
Darland,
The orphanin FQ system: an emerging target for the management of pain?
1998,
Pubmed
Ehresmann,
Probing the structure of RNAs in solution.
1987,
Pubmed
Ellington,
In vitro selection of RNA molecules that bind specific ligands.
1990,
Pubmed
Gold,
Oligonucleotides as research, diagnostic, and therapeutic agents.
1995,
Pubmed
Green,
Nuclease-resistant nucleic acid ligands to vascular permeability factor/vascular endothelial growth factor.
1995,
Pubmed
Griebel,
Orphanin FQ, a novel neuropeptide with anti-stress-like activity.
1999,
Pubmed
Grisel,
Effects of supraspinal orphanin FQ/nociceptin.
2000,
Pubmed
Guerrini,
A new selective antagonist of the nociceptin receptor.
1998,
Pubmed
Henderson,
The orphan opioid receptor and its endogenous ligand--nociceptin/orphanin FQ.
1997,
Pubmed
Ikeda,
Functional coupling of the nociceptin/orphanin FQ receptor with the G-protein-activated K+ (GIRK) channel.
1997,
Pubmed
,
Xenbase
Jayasena,
Aptamers: an emerging class of molecules that rival antibodies in diagnostics.
1999,
Pubmed
Kamei,
Antinociceptive effects of the ORL1 receptor agonist nociceptin/orphanin FQ in diabetic mice.
1999,
Pubmed
Klussmann,
Mirror-image RNA that binds D-adenosine.
1996,
Pubmed
Kubik,
Isolation and characterization of 2'-fluoro-, 2'-amino-, and 2'-fluoro-/amino-modified RNA ligands to human IFN-gamma that inhibit receptor binding.
1997,
Pubmed
Leva,
GnRH binding RNA and DNA Spiegelmers: a novel approach toward GnRH antagonism.
2002,
Pubmed
Lin,
Modified RNA sequence pools for in vitro selection.
1994,
Pubmed
Meunier,
Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor.
1995,
Pubmed
Meunier,
Nociceptin/orphanin FQ and the opioid receptor-like ORL1 receptor.
1997,
Pubmed
Mogil,
The molecular and behavioral pharmacology of the orphanin FQ/nociceptin peptide and receptor family.
2001,
Pubmed
Mollereau,
Tissue distribution of the opioid receptor-like (ORL1) receptor.
2000,
Pubmed
Monteillet-Agius,
ORL-1 and mu opioid receptor antisera label different fibers in areas involved in pain processing.
1998,
Pubmed
Nawrath,
Voltage dependence of L-arginine transport by hCAT-2A and hCAT-2B expressed in oocytes from Xenopus laevis.
2000,
Pubmed
,
Xenbase
Neal,
Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat.
1999,
Pubmed
Nieuwlandt,
In vitro selection of RNA ligands to substance P.
1995,
Pubmed
Nolte,
Mirror-design of L-oligonucleotide ligands binding to L-arginine.
1996,
Pubmed
Pagratis,
Potent 2'-amino-, and 2'-fluoro-2'-deoxyribonucleotide RNA inhibitors of keratinocyte growth factor.
1997,
Pubmed
Reinscheid,
Orphanin FQ: a neuropeptide that activates an opioidlike G protein-coupled receptor.
1995,
Pubmed
Reinscheid,
The orphanin FQ/nociceptin gene: structure, tissue distribution of expression and functional implications obtained from knockout mice.
2000,
Pubmed
Rizzi,
The nociceptin/orphanin FQ receptor antagonist, [Nphe1]NC(1-13)NH2, potentiates morphine analgesia.
2000,
Pubmed
Robertson,
Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA.
1990,
Pubmed
Rowsell,
Crystal structures of a series of RNA aptamers complexed to the same protein target.
1998,
Pubmed
Röver,
ORL1 receptor ligands: structure-activity relationships of 8-cycloalkyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-ones.
2000,
Pubmed
Röver,
High-affinity, non-peptide agonists for the ORL1 (orphanin FQ/nociceptin) receptor.
2000,
Pubmed
Salvadori,
Solution conformation of nociceptin.
1997,
Pubmed
Tian,
Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat.
1997,
Pubmed
Tian,
Endogenous orphanin FQ: evidence for a role in the modulation of electroacupuncture analgesia and the development of tolerance to analgesia produced by morphine and electroacupuncture.
1998,
Pubmed
Tian,
Functional studies using antibodies against orphanin FQ/nociceptin.
2000,
Pubmed
Toulmé,
Aptamers: selected oligonucleotides for therapy.
2000,
Pubmed
Tuerk,
Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase.
1990,
Pubmed
Urata,
Synthesis and properties of mirror-image DNA.
1992,
Pubmed
Vater,
Toward third-generation aptamers: Spiegelmers and their therapeutic prospects.
2003,
Pubmed
Williams,
Bioactive and nuclease-resistant L-DNA ligand of vasopressin.
1997,
Pubmed
Wilson,
In vitro selection of functional nucleic acids.
1999,
Pubmed
Wnendt,
Agonistic effect of buprenorphine in a nociceptin/OFQ receptor-triggered reporter gene assay.
1999,
Pubmed
Xu,
Anti-peptide aptamers recognize amino acid sequence and bind a protein epitope.
1996,
Pubmed
Ye,
RNA architecture dictates the conformations of a bound peptide.
1999,
Pubmed
