ArticleEuropean neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology2019
Rubiscolins are naturally occurring G protein-biased delta opioid receptor peptides.
Article in European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Discovery of Potent Kappa Opioid Receptor Agonists Derived from Akuammicine.Journal of medicinal chemistry · 2024Article
- Identification of 1,3,8-Triazaspiro[4.5]Decane-2,4-Dione Derivatives as a NovelThe Journal of pharmacology and experimental therapeutics · 2024Article
- Neuroprotective and Anti-inflammatory Effects of Rubiscolin-6 Analogs with Proline Surrogates in Position 2.Neurochemical research · 2024Article
- Descriptive molecular pharmacology of the δ opioid receptor (DOR): A computational study with structural approach.PloS one · 2024Article
- From Plant to Chemistry: Sources of Active Opioid Antinociceptive Principles for Medicinal Chemistry and Drug Design.Molecules (Basel, Switzerland) · 2023Review
- Modified Akuamma Alkaloids with Increased Potency at the Mu-opioid Receptor.Journal of medicinal chemistry · 2023Article
- A General Strategy to Install Amidine Functional Groups Along the Peptide Backbone.Journal of the American Chemical Society · 2022Article
- Opportunities and Challenges for In Silico Drug Discovery at Delta Opioid Receptors.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Opioids and Their Receptors: Present and Emerging Concepts in Opioid Drug Discovery II.Molecules (Basel, Switzerland) · 2022Article
- Exploration of beta-arrestin isoform signaling pathways in delta opioid receptor agonist-induced convulsions.Frontiers in pharmacology · 2022Article
- Identification of a Novel Delta Opioid Receptor Agonist Chemotype with Potential Negative Allosteric Modulator Capabilities.Molecules (Basel, Switzerland) · 2021Article
- Modulating β-arrestin 2 recruitment at the δ- and μ-opioid receptors using peptidomimetic ligands.RSC medicinal chemistry · 2021Article
- A new side-effect of sufentanil: increased monocyte-endothelial adhesion.BMC anesthesiology · 2021Article
- In Vitro Analyses of Spinach-Derived Opioid Peptides, Rubiscolins: Receptor Selectivity and Intracellular Activities through G Protein- and β-Arrestin-Mediated Pathways.Molecules (Basel, Switzerland) · 2021Article
- A Novel Mitragynine Analog with Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception with Attenuated Adverse Effects.Journal of medicinal chemistry · 2021Article
- Casomorphins and Gliadorphins Have Diverse Systemic Effects Spanning Gut, Brain and Internal Organs.International journal of environmental research and public health · 2021Article
- Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.RSC medicinal chemistry · 2021Review
- Isolation and Pharmacological Characterization of Six OpioidergicJournal of natural products · 2021Article
- Evaluation of Kratom Opioid Derivatives as Potential Treatment Option for Alcohol Use Disorder.Frontiers in pharmacology · 2021Article
- G protein-biased kratom-alkaloids and synthetic carfentanil-amide opioids as potential treatments for alcohol use disorder.British journal of pharmacology · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The impact that β-arrestin proteins have on G protein-coupled receptor trafficking, signaling and physiological behavior has gained much appreciation over the past decade. A number of studies have attributed the side effects associated with the use of naturally occurring and synthetic opioids, such as respiratory depression and constipation, to excessive recruitment of β-arrestin. These findings have led to the development of biased opioid small molecule agonists that do not recruit β-arrestin, activating only the canonical G protein pathway. Similar G protein-biased small molecule opioids have been found to occur in nature, particularly within kratom, and opioids within salvia have served as a template for the synthesis of other G protein-biased opioids. Here, we present the first report of naturally occurring peptides that selectively activate G protein signaling pathways at δ opioid receptors, but with minimal β-arrestin recruitment. Specifically, we find that rubiscolin peptides, which are produced as cleavage products of the plant protein rubisco, bind to and activate G protein signaling at δ opioid receptors. However, unlike the naturally occurring δ opioid peptides leu-enkephalin and deltorphin II, the rubiscolin peptides only very weakly recruit β-arrestin 2 and have undetectable recruitment of β-arrestin 1 at the δ opioid receptor.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.