ArticleFrontiers in pharmacology2015
A marine analgesic peptide, Contulakin-G, and neurotensin are distinct agonists for neurotensin receptors: uncovering structural determinants of desensitization properties.
Article in Frontiers in pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- From neuropeptides to toxins: illuminating the origins of venom complexity in cone snails.Molecular biology and evolution · 2026Article
- From marine predator to pharmacology: Conotoxin diversity, discovery, and therapeutic potential.Zoological research · 2026Review
- Toxins in disguise: Neuropeptide mimicry across animal venoms.General and comparative endocrinology · 2026Review
- Molecular Insights into the Marine GastropodInternational journal of molecular sciences · 2025Article
- Side-Chain Modified [International journal of molecular sciences · 2023Article
- Toward Stability Enhancement of NTSPharmaceutics · 2023Article
- Modern venomics-Current insights, novel methods, and future perspectives in biological and applied animal venom research.GigaScience · 2022Article
- Isolation and characterization of five novel disulfide-poor conopeptides fromThe journal of venomous animals and toxins including tropical diseases · 2022Article
- Structural and Functional Diversity of Animal Toxins Interacting With GPCRs.Frontiers in molecular biosciences · 2022Review
- Mollusc N-glycosylation: Structures, Functions and Perspectives.Biomolecules · 2021Review
- Strategies for Heterologous Expression, Synthesis, and Purification of Animal Venom Toxins.Frontiers in bioengineering and biotechnology · 2021Review
- Therapeutic Potential of Peptides Derived from Animal Venoms: Current Views and Emerging Drugs for Diabetes.Clinical medicine insights. Endocrinology and diabetes · 2021Review
- Glycopeptide drugs: A pharmacological dimension between "Small Molecules" and "Biologics".Peptides · 2020Review
- Snails In Silico: A Review of Computational Studies on the Conopeptides.Marine drugs · 2019Review
- Discovery Methodology of Novel Conotoxins fromMarine drugs · 2018Review
- Phosphopeptidomics Reveals Differential Phosphorylation States and Novel SxE Phosphosite Motifs of Neuropeptides in Dense Core Secretory Vesicles.Journal of the American Society for Mass Spectrometry · 2018Article
- Review
- Peptides, Peptidomimetics, and Polypeptides from Marine Sources: A Wealth of Natural Sources for Pharmaceutical Applications.Marine drugs · 2017Review
- In the picture: disulfide-poor conopeptides, a class of pharmacologically interesting compounds.The journal of venomous animals and toxins including tropical diseases · 2016Review
- Prey-Capture Strategies of Fish-Hunting Cone Snails: Behavior, Neurobiology and Evolution.Brain, behavior and evolution · 2015Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Neurotensin receptors have been studied as molecular targets for the treatment of pain, schizophrenia, addiction, or cancer. Neurotensin (NT) and Contulakin-G, a glycopeptide isolated from a predatory cone snail Conus geographus, share a sequence similarity at the C-terminus, which is critical for activation of neurotensin receptors. Both peptides are potent analgesics, although affinity and agonist potency of Contulakin-G toward neurotensin receptors are significantly lower, as compared to those for NT. In this work, we show that the weaker agonist properties of Contulakin-G result in inducing significantly less desensitization of neurotensin receptors and preserving their cell-surface density. Structure-activity relationship (SAR) studies suggested that both glycosylation and charged amino acid residues in Contulakin-G or NT played important roles in desensitizing neurotensin receptors. Computational modeling studies of human neurotensin receptor NTS1 and Contulakin-G confirmed the role of glycosylation in weakening interactions with the receptors. Based on available SAR data, we designed, synthesized, and characterized an analog of Contulakin-G in which the glycosylated amino acid residue, Gal-GalNAc-Thr10, was replaced by memantine-Glu10 residue. This analog exhibited comparable agonist potency and weaker desensitization properties as compared to that of Contulakin-G, while producing analgesia in the animal model of acute pain following systemic administration. We discuss our study in the context of feasibility and safety of developing NT therapeutic agents with improved penetration across the blood-brain barrier. Our work supports engineering peptide-based agonists with diverse abilities to desensitize G-protein coupled receptors and further emphasizes opportunities for conotoxins as novel pharmacological tools and drug candidates.
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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.