One-step synthesis of photoaffinity probes for live-cell MS-based proteomics

Fallon, David J. and Lehmann, Stephanie and Chung, Chun-Wa and Phillipou, Alex and Eberl, Christian and Fantom, Ken G. M. and Zappacosta, Francesca and Patel, Vipulkumar K. and Bantscheff, Marcus and Schofield, Christopher J. and Tomkinson, Nicholas C. O. and Bush, Jacob T. (2021) One-step synthesis of photoaffinity probes for live-cell MS-based proteomics. Chemistry - A European Journal, 27 (71). pp. 17880-17888. ISSN 0947-6539 (https://doi.org/10.1002/chem.202102036)

[thumbnail of Fallon-etal-CE-2021-One-step-synthesis-of-photoaffinity-probes-for-live-cell]
Preview
 Text. Filename: Fallon_etal_CE_2021_One_step_synthesis_of_photoaffinity_probes_for_live_cell.pdf
Accepted Author Manuscript
Download (1MB)| Preview

Abstract

We present a one-step Ugi reaction protocol for the expedient synthesis of photoaffinity probes for live-cell MS-based proteomics. The reaction couples an amine affinity function with commonly used photoreactive groups, and a variety of handle functionalities. Using this technology, a series of pan-BET (BET: bromodomain and extra-terminal domain) selective bromodomain photoaffinity probes were obtained by parallel synthesis. Studies on the effects of photoreactive group, linker length and irradiation wavelength on photocrosslinking efficiency provide valuable insights into photoaffinity probe design. Optimal probes were progressed to MS-based proteomics to capture the BET family of proteins from live cells and reveal their potential on- and off-target profiles.

  • Item type:Article
    ID code:78341
    Dates:
    Date
    Event
    20 December 2021
    Published
    30 July 2021
    Published Online
    29 July 2021
    Accepted
    9 June 2021
    Submitted
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:01 Nov 2021 12:44
    Last modified:09 Apr 2024 02:45
    URI:https://strathprints.strath.ac.uk/id/eprint/78341
CORE (COnnecting REpositories)