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    Kaiser N, Mejuch T, Fedoryshchak R, Janning P, Tate EW, Waldmann Het al., 2019,

    Photoactivatable Myristic Acid Probes for UNC119-Cargo Interactions.

    , Chembiochem, Vol: 20, Pages: 134-139

    Protein myristoylation plays key roles in biological processes, for instance, in membrane attachment and activation of proteins and in mediating protein-protein and protein-lipid interactions. Furthermore, myristoylated proteins are involved in disorders, including cancer and viral infections. Therefore, new tools to study protein myristoylation are in high demand. Herein, we report the development of photoactivatable probes, based on a diazirine-substituted analogue of myristic acid. The probes bind to and, upon irradiation, covalently label the lipid-binding chaperone protein uncoordinated 119 (UNC119). UNC119 increases overall solubility and regulates specifically the transport of myristoylated proteins between intercellular membranes. The binding mode of the probes is similar to that of the myristate moiety, and the residues inside the hydrophobic pocket of UNC119 proteins that are critical for covalent binding have been identified. The interaction with UNC119 was also demonstrated in cell lysate by means of affinity enrichment. Moreover, it is shown that the myristate analogue can be incorporated into peptide substrates by N-myristoyl transferases of Leishmania and Trypanosoma protozoan parasites.

    Benns HJ, Tate EW, Child MA, 2019,

    Activity-Based Protein Profiling for the Study of Parasite Biology.

    , Curr Top Microbiol Immunol, Vol: 420, Pages: 155-174, ISSN: 0070-217X

    Parasites exist within most ecological niches, often transitioning through biologically and chemically complex host environments over the course of their parasitic life cycles. While the development of technologies for genetic engineering has revolutionised the field of functional genomics, parasites have historically been less amenable to such modification. In light of this, parasitologists have often been at the forefront of adopting new small-molecule technologies, repurposing drugs into biological tools and probes. Over the last decade, activity-based protein profiling (ABPP) has evolved into a powerful and versatile chemical proteomic platform for characterising the function of enzymes. Central to ABPP is the use of activity-based probes (ABPs), which covalently modify the active sites of enzyme classes ranging from serine hydrolases to glycosidases. The application of ABPP to cellular systems has contributed vastly to our knowledge on the fundamental biology of a diverse range of organisms and has facilitated the identification of potential drug targets in many pathogens. In this chapter, we provide a comprehensive review on the different forms of ABPP that have been successfully applied to parasite systems, and highlight key biological insights that have been enabled through their application.

    Wang Z, Grosskurth SE, Cheung T, Petteruti P, Zhang J, Wang X, Wang W, Gharahdaghi F, Wu J, Su N, Howard RT, Mayo M, Widzowski D, Scott DA, Johannes JW, Lamb ML, Lawson D, Dry JR, Lyne PD, Tate EW, Zinda M, Mikule K, Fawell SE, Reimer C, Chen Het al., 2018,

    Pharmacological Inhibition of PARP6 Triggers Multipolar Spindle Formation and Elicits Therapeutic Effects in Breast Cancer

    , CANCER RESEARCH, Vol: 78, Pages: 6691-6702, ISSN: 0008-5472
    De Vita E, Schuler P, Lovell S, Lohbeck J, Kullmann S, Rabinovich E, Sananes A, Hessling B, Hamon V, Papo N, Hess J, Tate EW, Gunkel N, Miller AKet al., 2018,

    Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity

    , JOURNAL OF MEDICINAL CHEMISTRY, Vol: 61, Pages: 8859-8874, ISSN: 0022-2623
    Beard R, Singh N, Grundschober C, Gee AD, Tate EWet al., 2018,

    High-yielding F-18 radiosynthesis of a novel oxytocin receptor tracer, a probe for nose-to-brain oxytocin uptake in vivo

    , CHEMICAL COMMUNICATIONS, Vol: 54, Pages: 8120-8123, ISSN: 1359-7345
    Beard R, Stucki A, Schmitt M, Py G, Grundschober C, Gee AD, Tate EWet al., 2018,

    Building bridges for highly selective, potent and stable oxytocin and vasopressin analogs

    , BIOORGANIC & MEDICINAL CHEMISTRY, Vol: 26, Pages: 3039-3045, ISSN: 0968-0896
    Tate EW, 2018,

    Protein N terminal modifications: from chemical biology to drug discovery

    , Publisher: WILEY, Pages: 72-73, ISSN: 2211-5463
    Riviere F, Dian C, Perez-Dorado I, Ritzefeld M, Shen J, Cota E, Meinnel T, Tate EW, Giglione Cet al., 2018,

    Mechanistic insight into HsNMT1-mediated acylation

    , Publisher: WILEY, Pages: 421-422, ISSN: 2211-5463
    Mousnier A, Bell AS, Swieboda DP, Morales-Sanfrutos J, Perez-Dorado I, Brannigan JA, Newman J, Ritzefeld M, Hutton JA, Guedan A, Asfor AS, Robinson SW, Hopkins-Navratilova I, Wilkinson AJ, Johnston SL, Leatherbarrow RJ, Tuthill TJ, Solari R, Tate EWet al., 2018,

    Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus

    , NATURE CHEMISTRY, Vol: 10, Pages: 599-606, ISSN: 1755-4330
    Craven GB, Affron DP, Allen CE, Matthies S, Greener JG, Morgan RML, Tate EW, Armstrong A, Mann DJet al., 2018,

    High-Throughput Kinetic Analysis for Target-Directed Covalent Ligand Discovery

    , ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 57, Pages: 5257-5261, ISSN: 1433-7851

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