IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38541-2.html
   My bibliography  Save this article

Characterisation of IL-23 receptor antagonists and disease relevant mutants using fluorescent probes

Author

Listed:
  • Charles S. Lay

    (University of Nottingham
    University of Birmingham and Nottingham
    GlaxoSmithKline)

  • Albert Isidro-Llobet

    (GlaxoSmithKline)

  • Laura E. Kilpatrick

    (University of Birmingham and Nottingham
    University of Nottingham)

  • Peter D. Craggs

    (GlaxoSmithKline
    GlaxoSmithKline)

  • Stephen J. Hill

    (University of Nottingham
    University of Birmingham and Nottingham)

Abstract

Association of single nucleotide polymorphisms in the IL-23 receptor with several auto-inflammatory diseases, led to the heterodimeric receptor and its cytokine-ligand IL-23, becoming important drug targets. Successful antibody-based therapies directed against the cytokine have been licenced and a class of small peptide antagonists of the receptor have entered clinical trials. These peptide antagonists may offer therapeutic advantages over existing anti-IL-23 therapies, but little is known about their molecular pharmacology. In this study, we use a fluorescent version of IL-23 to characterise antagonists of the full-length receptor expressed by living cells using a NanoBRET competition assay. We then develop a cyclic peptide fluorescent probe, specific to the IL23p19:IL23R interface and use this molecule to characterise further receptor antagonists. Finally, we use the assays to study the immunocompromising C115Y IL23R mutation, demonstrating that the mechanism of action is a disruption of the binding epitope for IL23p19.

Suggested Citation

  • Charles S. Lay & Albert Isidro-Llobet & Laura E. Kilpatrick & Peter D. Craggs & Stephen J. Hill, 2023. "Characterisation of IL-23 receptor antagonists and disease relevant mutants using fluorescent probes," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38541-2
    DOI: 10.1038/s41467-023-38541-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38541-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38541-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38541-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.