ArticleNature communications2023
Design and structural validation of peptide-drug conjugate ligands of the kappa-opioid receptor.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed.
- Structural and functional basis of antinociceptive action of χ-conotoxin AoIA at the noradrenaline transporter.Nature structural & molecular biology · 2026Article
- Advances in Cyclic Peptides Targeting G Protein-Coupled Receptors.Chembiochem : a European journal of chemical biology · 2026Review
- De novo design of miniproteins targeting GPCRs.Nature · 2026Article
- Development and Biological Characterization of Fluorescent Dynorphins for the Visualization of Kappa Opioid Receptors.Journal of medicinal chemistry · 2026Article
- Identification of Subtype-Selective Binding Sites in the Opioid Receptor Family.Journal of chemical information and modeling · 2026Article
- A generalizable assay for intracellular accumulation to profile cytosolic drug delivery in mammalian cells.Communications chemistry · 2026Article
- Oxycodone versus Sufentanil for Postoperative Analgesia and Early Recovery After Radical Gastrectomy: A Propensity Score-Matched Study.Drug design, development and therapy · 2026Article
- Deep learning-enabled design of macrocyclic peptide binders.Nature chemical biology · 2025Article
- Somatostatin receptor 2 targeting peptide modifications for peptide-drug conjugate treatment of small cell lung cancer.Acta pharmacologica Sinica · 2025Article
- Accurate de novo design of high-affinity protein-binding macrocycles using deep learning.Nature chemical biology · 2025Article
- Elucidating biased signaling in class A GPCRs.Trends in pharmacological sciences · 2025Review
- κ-Opioid Receptor Agonists as Robust Pain-Modulating Agents: Mechanisms and Therapeutic Potential in Pain Modulation.Journal of clinical medicine · 2025Review
- PD-L1-targeted polymer-peptide-immune nanomedicine synergizes radiotherapy for durable tumor control.Bioactive materials · 2025Article
- Engineering Peptide Modulators for T-Cell Migration by Structural Scaffold Matching.Journal of medicinal chemistry · 2025Article
- Systematic Determination of the Impact of Structural Edits on Peptide Accumulation into Mycobacteria.ACS chemical biology · 2025Article
- Article
- Discovery of Potent Kappa Opioid Receptor Agonists Derived from Akuammicine.Journal of medicinal chemistry · 2024Article
- cyclicpeptide: a Python package for cyclic peptide drug design.Briefings in bioinformatics · 2024Article
- AccuratebioRxiv : the preprint server for biology · 2024Article
- A Bicyclic Analog of the Linear Peptide Arodyn Is a Potent and Selective Kappa Opioid Receptor Antagonist.Molecules (Basel, Switzerland) · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors.
Funding
Abstract
Despite the increasing number of GPCR structures and recent advances in peptide design, the development of efficient technologies allowing rational design of high-affinity peptide ligands for single GPCRs remains an unmet challenge. Here, we develop a computational approach for designing conjugates of lariat-shaped macrocyclized peptides and a small molecule opioid ligand. We demonstrate its feasibility by discovering chemical scaffolds for the kappa-opioid receptor (KOR) with desired pharmacological activities. The designed De Novo Cyclic Peptide (DNCP)-β-naloxamine (NalA) exhibit in vitro potent mixed KOR agonism/mu-opioid receptor (MOR) antagonism, nanomolar binding affinity, selectivity, and efficacy bias at KOR. Proof-of-concept in vivo efficacy studies demonstrate that DNCP-β-NalA(1) induces a potent KOR-mediated antinociception in male mice. The high-resolution cryo-EM structure (2.6 Å) of the DNCP-β-NalA-KOR-Gi1 complex and molecular dynamics simulations are harnessed to validate the computational design model. This reveals a network of residues in ECL2/3 and TM6/7 controlling the intrinsic efficacy of KOR. In general, our computational de novo platform overcomes extensive lead optimization encountered in ultra-large library docking and virtual small molecule screening campaigns and offers innovation for GPCR ligand discovery. This may drive the development of next-generation therapeutics for medical applications such as pain conditions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.