The Tate group utilises chemical probes as a core approach to understanding and interacting with living systems. We seek to redfine the chemical biology toolset to rapidly interrogate biological pathways and identify critical protein targets.
The image above (adapted from Howard et al 2020) demonstrates a probe which is designed from a parent compound (grey ball) with unknown interacting partners inside the cell. The photoaffinity probe can enter live cells and bind to the same targets as the parent compound. Irradiation with long wavelength UV light causes the photoreactive group to unmask and produce a highly reactive intermediate which forms a permanent covalent bond between probe and protein. Once cells are lysed, the probe's bio-orthogonal handle can be used to ligate probe-tagged proteins to a fluorescent- and/or enrichment-based reporter molecule. These reporter molecules then allow for qualitative and quantitative profiling of the probe-engaged targets through gel- and proteomics-based methods. [CuAAC = Cu-catalysed azide-alkyne cycloaddition; DMSO = dimethyl sulphoxide; LC-MS/MS - liquid chromatography-tandem mass spectrometry; UV = ultraviolet]. For more information on this study, see Howard et al (2020).
See below for other Tate group publications that utilise chemical probes.
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24 February 2020A cell-active probe for PARP inhibitors