IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-53240-2.html
   My bibliography  Save this article

Streamlined analysis of drug targets by proteome integral solubility alteration indicates organ-specific engagement

Author

Listed:
  • Tanveer Singh Batth

    (University of Copenhagen)

  • Marie Locard-Paulet

    (University of Copenhagen
    Université Toulouse III - Paul Sabatier (UT3))

  • Nadezhda T. Doncheva

    (University of Copenhagen)

  • Blanca Lopez Mendez

    (University of Copenhagen)

  • Lars Juhl Jensen

    (University of Copenhagen)

  • Jesper Velgaard Olsen

    (University of Copenhagen)

Abstract

Proteins are the primary targets of almost all small molecule drugs. However, even the most selectively designed drugs can potentially target several unknown proteins. Identification of potential drug targets can facilitate design of new drugs and repurposing of existing ones. Current state-of-the-art proteomics methodologies enable screening of thousands of proteins against a limited number of drug molecules. Here we report the development of a label-free quantitative proteomics approach that enables proteome-wide screening of small organic molecules in a scalable, reproducible, and rapid manner by streamlining the proteome integral solubility alteration (PISA) assay. We used rat organs ex-vivo to determine organ specific targets of medical drugs and enzyme inhibitors to identify drug targets for common drugs such as Ibuprofen. Finally, global drug profiling revealed overarching trends of how small molecules affect the proteome through either direct or indirect protein interactions.

Suggested Citation

  • Tanveer Singh Batth & Marie Locard-Paulet & Nadezhda T. Doncheva & Blanca Lopez Mendez & Lars Juhl Jensen & Jesper Velgaard Olsen, 2024. "Streamlined analysis of drug targets by proteome integral solubility alteration indicates organ-specific engagement," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53240-2
    DOI: 10.1038/s41467-024-53240-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-53240-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-53240-2?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
    ---><---

    References listed on IDEAS

    as
    1. Ana Martinez-Val & Dorte B. Bekker-Jensen & Sophia Steigerwald & Claire Koenig & Ole Østergaard & Adi Mehta & Trung Tran & Krzysztof Sikorski & Estefanía Torres-Vega & Ewa Kwasniewicz & Sólveig Hlín B, 2021. "Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    2. Jasper Edgar Neggers & Bert Kwanten & Tim Dierckx & Hiroki Noguchi & Arnout Voet & Lotte Bral & Kristien Minner & Bob Massant & Nicolas Kint & Michel Delforge & Thomas Vercruysse & Erkan Baloglu & Wil, 2018. "Target identification of small molecules using large-scale CRISPR-Cas mutagenesis scanning of essential genes," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Julia P. Schessner & Vincent Albrecht & Alexandra K. Davies & Pavel Sinitcyn & Georg H. H. Borner, 2023. "Deep and fast label-free Dynamic Organellar Mapping," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Henrik M. Hammarén & Eva-Maria Geissen & Clement M. Potel & Martin Beck & Mikhail M. Savitski, 2022. "Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Joanne Watson & Harriet R. Ferguson & Rosie M. Brady & Jennifer Ferguson & Paul Fullwood & Hanyi Mo & Katherine H. Bexley & David Knight & Gareth Howell & Jean-Marc Schwartz & Michael P. Smith & Chiar, 2022. "Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival," Nature Communications, Nature, vol. 13(1), pages 1-22, December.

    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:15:y:2024:i:1:d:10.1038_s41467-024-53240-2. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.