119 results found
Clulow JA, Storck EM, Lanyon-Hogg T, et al., 2017, Competition-based, quantitative chemical proteomics in breast cancer cells identifies new target profiles for sulforaphane, CHEMICAL COMMUNICATIONS, Vol: 53, Pages: 5182-5185, ISSN: 1359-7345
Demetriadou A, Morales-Sanfrutos J, Nearchou M, et al., 2017, Mouse Stbd1 is N-myristoylated and affects ER-mitochondria association and mitochondrial morphology, JOURNAL OF CELL SCIENCE, Vol: 130, Pages: 903-915, ISSN: 0021-9533
Duluc L, Ahmetaj-Shala B, Mitchell J, et al., 2017, Tipifarnib prevents development of hypoxia-induced pulmonary hypertension, CARDIOVASCULAR RESEARCH, Vol: 113, Pages: 276-287, ISSN: 0008-6363
Gorlitz F, Kelly DJ, Warren SC, et al., 2017, Open Source High Content Analysis Utilizing Automated Fluorescence Lifetime Imaging Microscopy, JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, ISSN: 1940-087X
Lanyon-Hogg T, Faronato M, Serwa RA, et al., 2017, Dynamic protein acylation: new substrates, mechanisms and drug targets, Trends in Biochemical Sciences, Vol: 42, Pages: 566-581, ISSN: 0968-0004
Post-translational attachment of lipids to proteins is found in all organisms, and is important for many biological processes. Acylation with myristic and palmitic acids are among the most common lipid modifications, and understanding reversible protein palmitoylation dynamics has become a particularly important goal. Linking acyltransferase enzymes to disease states can be challenging due to a paucity of robust models, compounded by functional redundancy between many palmitoyl transferases; however, in cases such as Wnt or Hedgehog signalling, small molecule inhibitors have been identified, with some progressing to clinical trials. In this review, we present recent developments in our understanding of protein acylation in human health and disease through use of chemical tools, global profiling of acylated proteomes, and functional studies of specific protein targets.
Lanyon-Hogg T, Patel NV, Ritzefeld M, et al., 2017, Microfluidic Mobility Shift Assay for Real-Time Analysis of Peptide N-Palmitoylation, SLAS DISCOVERY, Vol: 22, Pages: 418-424, ISSN: 2472-5552
Perdios L, Lowe AR, Saladino G, et al., 2017, Conformational transition of FGFR kinase activation revealed by site-specific unnatural amino acid reporter and single molecule FRET, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322
Ritzefeld M, Wright MH, Tate EW, 2017, New developments in probing and targeting protein acylation in malaria, leishmaniasis and African sleeping sickness., Parasitology, Pages: 1-18
Infections by protozoan parasites, such as Plasmodium falciparum or Leishmania donovani, have a significant health, social and economic impact and threaten billions of people living in tropical and sub-tropical regions of developing countries worldwide. The increasing range of parasite strains resistant to frontline therapeutics makes the identification of novel drug targets and the development of corresponding inhibitors vital. Post-translational modifications (PTMs) are important modulators of biology and inhibition of protein lipidation has emerged as a promising therapeutic strategy for treatment of parasitic diseases. In this review we summarize the latest insights into protein lipidation in protozoan parasites. We discuss how recent chemical proteomic approaches have delivered the first global overviews of protein lipidation in these organisms, contributing to our understanding of the role of this PTM in critical metabolic and cellular functions. Additionally, we highlight the development of new small molecule inhibitors to target parasite acyl transferases.
Zhao W, Jamshidiha M, Lanyon-Hogg T, et al., 2017, Direct Targeting of the Ras GTPase Superfamily Through Structure-Based Design, CURRENT TOPICS IN MEDICINAL CHEMISTRY, Vol: 17, Pages: 16-29, ISSN: 1568-0266
Albrow VE, Grimley RL, Clulow J, et al., 2016, Design and development of histone deacetylase (HDAC) chemical probes for cell-based profiling, MOLECULAR BIOSYSTEMS, Vol: 12, Pages: 1781-1789, ISSN: 1742-206X
Broncel M, Serwa RA, Bunney TD, et al., 2016, Global Profiling of Huntingtin-associated protein E (HYPE)-Mediated AMPylation through a Chemical Proteomic Approach, MOLECULAR & CELLULAR PROTEOMICS, Vol: 15, Pages: 715-725, ISSN: 1535-9476
Goncalves V, Brannigan JA, Laporte A, et al., 2016, Structure-guided optimization of quinoline inhibitors of Plasmodium N-myristoyltransferase, MedChemComm, Vol: 8, Pages: 191-197, ISSN: 2040-2511
The parasite Plasmodium vivax is the most widely distributed cause of recurring malaria. N-myristoyltransferase (NMT), an enzyme that catalyses the covalent attachment of myristate to the N-terminal glycine of substrate proteins, has been described as a potential target for the treatment of this disease. Herein, we report the synthesis and the structure-guided optimization of a series of quinolines with balanced activity against both Plasmodium vivax and Plasmodium falciparum N-myristoyltransferase (NMT).
Lanyon-Hogg T, Masumoto N, Bodakh G, et al., 2016, Synthesis and characterisation of 5-acyl-6,7-dihydrothieno[3,2-c]pyridine inhibitors of Hedgehog acyltransferase., Data Brief, Vol: 7, Pages: 257-281, ISSN: 2352-3409
In this data article we describe synthetic and characterisation data for four members of the 5-acyl-6,7-dihydrothieno[3,2-c]pyridine (termed "RU-SKI") class of inhibitors of Hedgehog acyltransferase, including associated NMR spectra for final compounds. RU-SKI compounds were selected for synthesis based on their published high potencies against the enzyme target. RU-SKI 41 (9a), RU-SKI 43 (9b), RU-SKI 101 (9c), and RU-SKI 201 (9d) were profiled for activity in the related article "Click chemistry armed enzyme linked immunosorbent assay to measure palmitoylation by Hedgehog acyltransferase" (Lanyon-Hogg et al., 2015) . (1)H NMR spectral data indicate different amide conformational ratios between the RU-SKI inhibitors, as has been observed in other 5-acyl-6,7-dihydrothieno[3,2-c]pyridines. The synthetic and characterisation data supplied in the current article provide validated access to the class of RU-SKI inhibitors.
Perdios L, Bunney TD, Warren SC, et al., 2016, Time-resolved FRET reports FGFR1 dimerization and formation of a complex with its effector PLCγ1., Adv Biol Regul, Vol: 60, Pages: 6-13
In vitro and in vivo imaging of protein tyrosine kinase activity requires minimally invasive, molecularly precise optical probes to provide spatiotemporal mechanistic information of dimerization and complex formation with downstream effectors. We present here a construct with genetically encoded, site-specifically incorporated, bioorthogonal reporter that can be selectively labelled with exogenous fluorogenic probes to monitor the structure and function of fibroblast growth factor receptor (FGFR). GyrB.FGFR1KD.TC contains a coumermycin-induced artificial dimerizer (GyrB), FGFR1 kinase domain (KD) and a tetracysteine (TC) motif that enables fluorescent labelling with biarsenical dyes FlAsH-EDT2 and ReAsH-EDT2. We generated bimolecular system for time-resolved FRET (TR-FRET) studies, which pairs FlAsH-tagged GyrB.FGFR1KD.TC and N-terminal Src homology 2 (nSH2) domain of phospholipase Cγ (PLCγ), a downstream effector of FGFR1, fused to mTurquoise fluorescent protein (mTFP). We demonstrated phosphorylation-dependent TR-FRET readout of complex formation between mTFP.nSH2 and GyrB.FGFR1KD.TC. By further application of TR-FRET, we also demonstrated formation of the GyrB.FGFR1KD.TC homodimer by coumermycin-induced dimerization. Herein, we present a spectroscopic FRET approach to facilitate and propagate studies that would provide structural and functional insights for FGFR and other tyrosine kinases.
Rodgers UR, Lanyon-Hogg T, Masumoto N, et al., 2016, Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells, ACS CHEMICAL BIOLOGY, Vol: 11, Pages: 3256-3262, ISSN: 1554-8929
So EC, Schroeder GN, Carson D, et al., 2016, The Rab-binding Profiles of Bacterial Virulence Factors during Infection, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 291, Pages: 5832-5843, ISSN: 0021-9258
Thinon E, Morales-Sanfrutos J, Mann DJ, et al., 2016, N-Myristoyltransferase Inhibition Induces ER-Stress, Cell Cycle Arrest, and Apoptosis in Cancer Cells, ACS CHEMICAL BIOLOGY, Vol: 11, Pages: 2165-2176, ISSN: 1554-8929
Ward JA, McLellan L, Stockley M, et al., 2016, Quantitative Chemical Proteomic Profiling of Ubiquitin Specific Proteases in Intact Cancer Cells, ACS CHEMICAL BIOLOGY, Vol: 11, Pages: 3268-3272, ISSN: 1554-8929
Wright MH, Paape D, Price HP, et al., 2016, Global Profiling and Inhibition of Protein Lipidation in Vector and Host Stages of the Sleeping Sickness Parasite Trypanosoma brucei, ACS INFECTIOUS DISEASES, Vol: 2, Pages: 427-441, ISSN: 2373-8227
Broncel M, Serwa RA, Ciepla P, et al., 2015, Multifunctional Reagents for Quantitative Proteome-Wide Analysis of Protein Modification in Human Cells and Dynamic Profiling of Protein Lipidation During Vertebrate Development, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 54, Pages: 5948-5951, ISSN: 1433-7851
Broncel M, Serwa RA, Ciepla P, et al., 2015, Myristoylation profiling in human cells and zebrafish., Data Brief, Vol: 4, Pages: 379-383, ISSN: 2352-3409
Human cells (HEK 293, HeLa, MCF-7) and zebrafish embryos were metabolically tagged with an alkynyl myristic acid probe, lysed with an SDS buffer and tagged proteomes ligated to multifunctional capture reagents via copper-catalyzed alkyne azide cycloaddition (CuAAC). This allowed for affinity enrichment and high-confidence identification, by delivering direct MS/MS evidence for the modification site, of 87 and 61 co-translationally myristoylated proteins in human cells and zebrafish, respectively. The data have been deposited to ProteomeXchange Consortium (Vizcaíno et al., 2014 Nat. Biotechnol., 32, 223-6) (PXD001863 and PXD001876) and are described in detail in Multifunctional reagents for quantitative proteome-wide analysis of protein modification in human cells and dynamic protein lipidation during vertebrate development׳ by Broncel et al., Angew. Chem. Int. Ed.
Charlton TM, Kovacs-Simon A, Michell SL, et al., 2015, Quantitative Lipoproteomics in Clostridium difficile Reveals a Role for Lipoproteins in Sporulation, CHEMISTRY & BIOLOGY, Vol: 22, Pages: 1562-1573, ISSN: 1074-5521
Ciepla P, Magee AI, Tate EW, 2015, Cholesterylation: a tail of hedgehog, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 43, Pages: 262-267, ISSN: 0300-5127
Douse CH, Vrielink N, Zhang W, et al., 2015, Targeting a Dynamic Protein-Protein Interaction: Fragment Screening against the Malaria Myosin A Motor Complex, CHEMMEDCHEM, Vol: 10, Pages: 134-143, ISSN: 1860-7179
Furse S, Mak L, Tate EW, et al., 2015, Synthesis of unsaturated phosphatidylinositol 4-phosphates and the effects of substrate unsaturation on SopB phosphatase activity, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 13, Pages: 2001-2011, ISSN: 1477-0520
Kalesh KA, Clulow JA, Tate EW, 2015, Target profiling of zerumbone using a novel cell-permeable clickable probe and quantitative chemical proteomics, CHEMICAL COMMUNICATIONS, Vol: 51, Pages: 5497-5500, ISSN: 1359-7345
Kelly DJ, Warren SC, Alibhai D, et al., 2015, Automated multiwell fluorescence lifetime imaging for Forster resonance energy transfer assays and high content analysis, ANALYTICAL METHODS, Vol: 7, Pages: 4071-4089, ISSN: 1759-9660
Konitsiotis AD, Jovanovic B, Ciepla P, et al., 2015, Topological Analysis of Hedgehog Acyltransferase, a Multipalmitoylated Transmembrane Protein, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 290, Pages: 3293-3307, ISSN: 0021-9258
Lanyon-Hogg T, Masumoto N, Bodakh G, et al., 2015, Click chemistry armed enzyme-linked immunosorbent assay to measure palmitoylation by hedgehog acyltransferase, ANALYTICAL BIOCHEMISTRY, Vol: 490, Pages: 66-72, ISSN: 0003-2697
Lanyon-Hogg T, Ritzefeld M, Masumoto N, et al., 2015, Modulation of Amide Bond Rotamers in 5-Acyl-6,7-dihydrothieno[3,2-c]pyridines, JOURNAL OF ORGANIC CHEMISTRY, Vol: 80, Pages: 4370-4377, ISSN: 0022-3263
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