ArticleACS chemical biology2009
Bivalent peptidomimetic ligands of TrkC are biased agonists and selectively induce neuritogenesis or potentiate neurotrophin-3 trophic signals.
Article in ACS chemical biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Molecular determinants of signal transduction in tropomyosin receptor kinases.FEBS open bio · 2026Review
- Selective Modulation of Trk Receptors byACS chemical neuroscience · 2025Article
- Study of the Pharmacological Activity Spectrum of the New Original NT-3 Mimetic Dipeptide GTS-302.Doklady. Biochemistry and biophysics · 2025Article
- Selective inhibitors of the TrkC.T1 receptor reduce retinal inflammation and delay neuronal death in a model of retinitis pigmentosa.PNAS nexus · 2025Article
- Selective, Intrinsically Fluorescent Trk Modulating Probes.ACS chemical neuroscience · 2024Article
- Antibody-dependent cellular phagocytosis of tropomyosin receptor kinase C (TrkC) expressing cancer cells for targeted immunotherapy.Cancer immunology, immunotherapy : CII · 2022Article
- A Photosensitized Singlet Oxygen (Molecules (Basel, Switzerland) · 2022Review
- Ligand bias in receptor tyrosine kinase signaling.The Journal of biological chemistry · 2020Review
- TrkC-Targeted Kinase Inhibitors And PROTACs.Molecular pharmaceutics · 2019Article
- Design criteria for minimalist mimics of protein-protein interface segments.Organic & biomolecular chemistry · 2019Article
- Neuroprotection: Pro-survival and Anti-neurotoxic Mechanisms as Therapeutic Strategies in Neurodegeneration.Frontiers in cellular neuroscience · 2019Review
- 1,4-Disubstituted 1Frontiers in chemistry · 2019Article
- Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression.Psychopharmacology · 2018Review
- Click-Addressable Cassette for Photoaffinity Labeling.ACS medicinal chemistry letters · 2018Article
- In retinitis pigmentosa TrkC.T1-dependent vectorial Erk activity upregulates glial TNF-α, causing selective neuronal death.Cell death & disease · 2017Article
- Novel Small Molecule Probes for Metastatic Melanoma.ACS medicinal chemistry letters · 2017Article
- Tropomyosin Receptor Kinase C Targeted Delivery of a Peptidomimetic Ligand-Photosensitizer Conjugate Induces Antitumor Immune Responses Following Photodynamic Therapy.Scientific reports · 2016Article
- The Paradoxical Signals of Two TrkC Receptor Isoforms Supports a Rationale for Novel Therapeutic Strategies in ALS.PloS one · 2016Article
- Targeted PDT agent eradicates TrkC expressing tumors via photodynamic therapy (PDT).Molecular pharmaceutics · 2015Article
- Combinatorial assembly of small molecules into bivalent antagonists of TrkC or TrkA receptors.PloS one · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
This study was initiated to find small molecule ligands that would induce a functional response when docked with neurotrophin Trk receptors. "Minimalist" mimics of beta-turns were designed for this purpose. These mimics are (i) rigid, yet easily folded into turn-like conformations, and (ii) readily accessible from amino acids bearing most of the natural side chains. Gram quantities of 16 of these turn mimics were prepared and then assembled into 152 fluorescein-labeled bivalent peptidomimetics via a solution-phase combinatorial method. Fluorescence-based screening of these molecules using cells transfected with the Trk receptors identified 10 potential ligands of TrkC, the receptor for neurotrophin-3. Analogues of these bivalent peptidomimetics with biotin replacing the fluorescein label were then prepared and tested to confirm that binding was not due to the fluorescein. Several assays were conducted to find the mode of action of these biotinylated compounds. Thus, direct binding, survival and neuritogenic, and biochemical signal transduction assays showed 8 of the original 10 hits were agonistic ligands binding to the ectodomain of TrkC. Remarkably, some peptidomimetics afford discrete signals leading to either cell survival or neuritogenic differentiation. The significance of this work is three-fold. First, we succeeded in finding small, selective, proteolytically stable ligands for the TrkC receptor; there are very few of these in the literature. Second, we show that it is possible to activate distinct and biased signaling pathways with ligands binding at the ectodomain of wild-type receptors. Third, the discovery that some peptidomimetics initiate different modes of cell signaling increases their potential as pharmacological probes and therapeutic leads.
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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.