Abstract:
The Tate lab develops novel chemical biology approaches to enable drug discovery against post-translational modification (PTM) pathways and intractable drug targets, including chemical proteomic target identification, screening technologies (10), and chemical probe discovery for protein-protein interactions and enzymes modulating PTMs (1,5,6). Recent highlights include the first cell-active activity-based probes (ABPs) for deubiquitinases (DUBs) (7), new tools for analysis and discovery of pathogenic secreted protease activities (3,4), and the first comprehensive maps of specific classes of protein lipidation PTM through chemical proteomics (11-13). We are also interested in new modalities including antibody-PROTAC conjugates (8), and translation of ultrapotent chemical probes into drug candidates (9,14,15).

Representative publications:

1. “Structure, mechanism, and inhibition of Hedgehog acyltransferase”, Mol Cell 2021, 81, 5025. Link.
2. “Proteome-wide analysis of protein lipidation using chemical probes”, Nature Protocols 2021, 16, 5083. Link.
3. “Substrate-biased activity-based probes identify proteases that cleave receptor CDCP1”, Nat Chem Biol 2021, 17, 776. Link.
4. “A suite of activity-based probes to dissect the KLK activome in drug-resistant prostate cancer”, J Am Chem Soc 2021, 143, 8911. Link.
5. “Identification of the first structurally validated covalent ligands of the small GTPase RAB27A”, RSC Med Chem 2021, 13, 150. Link.
6. “Photochemical probe identification of a small‐molecule inhibitor binding site in Hedgehog acyltransferase (HHAT)”, Angew Chemie 2021, 60, 13542. Link.
7. “Discovery of a Potent and Selective Covalent Inhibitor and Activity-Based Probe for the Deubiquitylating Enzyme UCHL1, with Antifibrotic Activity”, J Am Chem Soc 2020, 142, 12020. Link.
8. “Antibody-PROTAC Conjugates Enable HER2-Dependent Targeted Protein Degradation of BRD4”, ACS Chem. Biol. 2020, 15, 1306-1312. Link.
9. “High-resolution snapshots of human N-myristoyltransferase illuminate a unique mechanism promoting Lys and Gly myristoylation”, Nature Commun 2020, 11, 1132. Link.
10. “CRISPR-TAPE: protein-centric CRISPR guide design for targeted proteome engineering”, Mol Syst Biol 2020, 16, e9475. Link.
11. “FSP1 is a glutathione-independent ferroptosis suppressor”, Nature 2019, 575, 693. Link.
12. “Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics”, Nature Chemistry 2019, 11, 552-61. Link.
13. “Global profiling of co- and post-translationally N-myristoylated proteomes in human cells”, Nature Comms 2014, 5, 4919. Link.
14. “Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus”, Nature Chemistry 2018, 10, 599–606. Link.
15. "Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach", Nature Chemistry 2014, 6, 112-121. Link.

 Link to homepage:
https://www.imperial.ac.uk/tate-group/