PhotoAffinity bits : a photoaffinity-based fragment screening platform for efficient identification of protein ligands

Tools

Grant, Emma K. and Fallon, David J. and Hann, Michael M. and Fantom, Ken G. M. and Quinn, Chad and Zappacosta, Francesca and Annan, Roland S. and Cheung, Chun-Wa and Bamborough, Paul and Dixon, David P. and Stacey, Peter and House, David and Patel, Vipulkumar K. and Tomkinson, Nick C. O. and Bush, Jacob T. (2020) PhotoAffinity bits : a photoaffinity-based fragment screening platform for efficient identification of protein ligands. Preprint / Working Paper. ChemRxiv, Washington DC. (https://doi.org/10.26434/chemrxiv.12053445.v1)

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Abstract

Advances in genomic analyses enable the identification of new proteins that are associated with disease. To validate these targets, tool molecules are required to demonstrate that a ligand can have a disease-modifying effect. Currently, as tools are reported for only a fraction of the proteome, platforms for ligand discovery are essential to leverage insights from genomic analyses. Fragment screening offers an efficient approach to explore chemical space, however, it remains challenging to develop techniques that are both sufficiently high-throughput and sensitive. We present a fragment screening platform, termed PhABits (PhotoAffinity Bits), which utilises a library of photoreactive fragments to covalently capture fragment-protein interactions. Hits can be profiled to determine potency and site of crosslinking, and subsequently developed as reporters in a competitive displacement assay to identify novel hit matter. We envision that the PhABits will be widely applicable to novel protein targets, identifying starting points in the development of therapeutics

ORCID iDs

Grant, Emma K., Fallon, David J., Hann, Michael M., Fantom, Ken G. M., Quinn, Chad, Zappacosta, Francesca, Annan, Roland S., Cheung, Chun-Wa, Bamborough, Paul, Dixon, David P., Stacey, Peter, House, David, Patel, Vipulkumar K., Tomkinson, Nick C. O. ORCID logoORCID: https://orcid.org/0000-0002-5509-0133 and Bush, Jacob T.;
  • Item type:Monograph(Preprint / Working Paper)
    ID code:73345
    Dates:
    Date
    Event
    1 April 2020
    Published
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:27 Jul 2020 15:59
    Last modified:20 Dec 2024 01:12
    URI:https://strathprints.strath.ac.uk/id/eprint/73345
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