ArticleThe FEBS journal2015
N-Terminally extended analogues of the K⁺ channel toxin from Stichodactyla helianthus as potent and selective blockers of the voltage-gated potassium channel Kv1.3.
Article in The FEBS journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Reprogramming microglia via ShK-modified extracellular vesicles promotes immunomodulation and functional recovery after spinal cord injury.Journal of nanobiotechnology · 2026Article
- Large-Scale AI-Based Structure and Activity Prediction Analysis of ShK Domain Peptides from Sea Anemones in the South China Sea.Marine drugs · 2025Article
- Voltage-Gated KMarine drugs · 2024Review
- Article
- Structure of the voltage-gated potassium channel KChannels (Austin, Tex.) · 2023Review
- Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Optimization ofFrontiers in pharmacology · 2021Article
- Proteomic Analysis of the Venom of JellyfishesMarine drugs · 2020Article
- Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds.Marine drugs · 2020Review
- A Recurrent Motif: Diversity and Evolution of ShKT Domain Containing Proteins in the Vampire SnailToxins · 2019Article
- Review
- The antifungal plant defensin AtPDF2.3 from Arabidopsis thaliana blocks potassium channels.Scientific reports · 2016Article
- Study of Small-Molecule-Membrane Protein Binding Kinetics with Nanodisc and Charge-Sensitive Optical Detection.Analytical chemistry · 2016Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The voltage-gated potassium channel Kv1.3 is an important target for the treatment of autoimmune diseases and asthma. Blockade of Kv1.3 by the sea anemone peptide K⁺-channel toxin from Stichodactyla helianthus (ShK) inhibits the proliferation of effector memory T lymphocytes and ameliorates autoimmune diseases in animal models. However, the lack of selectivity of ShK for Kv1.3 over the Kv1.1 subtype has driven a search for Kv1.3-selective analogues. In the present study, we describe N-terminally extended analogues of ShK that contain a negatively-charged Glu, designed to mimic the phosphonate adduct in earlier Kv1.3-selective analogues, and consist entirely of common protein amino acids. Molecular dynamics simulations indicated that a Trp residue at position [-3] of the tetrapeptide extension could form stable interactions with Pro377 of Kv1.3 and best discriminates between Kv1.3 and Kv1.1. This led to the development of ShK with an N-terminal Glu-Trp-Ser-Ser extension ([EWSS]ShK), which inhibits Kv1.3 with an IC₅₀ of 34 pm and is 158-fold selective for Kv1.3 over Kv1.1. In addition, [EWSS]ShK is more than 2900-fold more selective for Kv1.3 over Kv1.2 and KCa3.1 channels. As a highly Kv1.3-selective analogue of ShK based entirely on protein amino acids, which can be produced by recombinant expression, this peptide is a valuable addition to the complement of therapeutic candidates for the treatment of autoimmune diseases.
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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.