1. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B.

    Journal of medicinal and pharmaceutical chemistry 59(4):1410 (2016) PMID 25799074 PMCID PMC4770311

    Bromodomains are acetyl-lysine specific protein interaction domains that have recently emerged as a new target class for the development of inhibitors that modulate gene transcription. The two closely related bromodomain containing proteins BAZ2A and BAZ2B constitute the central scaffolding prot...
  2. Thermal proteome profiling monitors ligand interactions with cellular membrane proteins.

    Nature Methods 12(12):1129 (2015) PMID 26524241

    We extended thermal proteome profiling to detect transmembrane protein-small molecule interactions in cultured human cells. When we assessed the effects of detergents on ATP-binding profiles, we observed shifts in denaturation temperature for ATP-binding transmembrane proteins. We also observed ...
  3. Thermal proteome profiling for unbiased identification of direct and indirect drug targets using multiplexed quantitative mass spectrometry.

    Nature Protocols 10(10):1567 (2015) PMID 26379230

    The direct detection of drug-protein interactions in living cells is a major challenge in drug discovery research. Recently, we introduced an approach termed thermal proteome profiling (TPP), which enables the monitoring of changes in protein thermal stability across the proteome using quantitat...
  4. Structure-Based Optimization of Naphthyridones into Potent ATAD2 Bromodomain Inhibitors.

    Journal of medicinal and pharmaceutical chemistry 58(15):6151 (2015) PMID 26230603

    ATAD2 is a bromodomain-containing protein whose overexpression is linked to poor outcomes in a number of different cancer types. To date, no potent and selective inhibitors of the bromodomain have been reported. This article describes the structure-based optimization of a series of naphthyridone...
  5. Ion coalescence of neutron encoded TMT 10-plex reporter ions.

    Analytical chemistry 86(7):3594 (2014) PMID 24579773

    Isobaric mass tag-based quantitative proteomics strategies such as iTRAQ and TMT utilize reporter ions in the low mass range of tandem MS spectra for relative quantification. The recent extension of TMT multiplexing to 10 conditions has been enabled by utilizing neutron encoded tags with reporte...
  6. The commonly used PI3-kinase probe LY294002 is an inhibitor of BET bromodomains.

    ACS Chemical Biology 9(2):495 (2014) PMID 24533473

    A commonly used small-molecule probe in cell-signaling research is the phosphoinositide 3-kinase inhibitor LY294002. Quantitative chemoproteomic profiling shows that LY294002 and LY303511, a close analogue devoid of PI3K activity, inhibit the BET bromodomain proteins BRD2, BRD3, and BRD4 that co...
  7. High-resolution enabled TMT 8-plexing.

    Analytical chemistry 84(16):7188 (2012) PMID 22881393

    Isobaric mass tag-based quantitative proteomics strategies such as iTRAQ and TMT utilize reporter ions in the low-mass range of tandem MS spectra for relative quantification. The number of samples that can be compared in a single experiment (multiplexing) is limited by the number of different re...
  8. Discovery of 5-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-N-(tert-butyl)pyridine-3-sulfonamide (CZC24758), as a potent, orally bioavailable and selective inhibitor of PI3K for the treatment of inflammatory disease

    Bioorganic & Medicinal Chemistry Letters 22(14):4613 (2012) PMID 22726925

    Herein, we disclose the discovery of a series of 7-substituted triazolopyridines which culminated in the identification of 14 (CZC24758), a potent, orally bioavailable small-molecule inhibitor of PI3Kγ, an attractive drug target for inflammatory and autoimmune disorders. Compound 14 has excellen...
  9. Discovery of 5-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-N-(tert-butyl)pyridine-3-sulfonamide (CZC24758), as a potent, orally bioavailable and selective inhibitor of PI3K for the treatment of inflammatory disease.

    Bioorganic & Medicinal Chemistry Letters 22(14):4613 (2012) PMID 22726925

    Herein, we disclose the discovery of a series of 7-substituted triazolopyridines which culminated in the identification of 14 (CZC24758), a potent, orally bioavailable small-molecule inhibitor of PI3Kγ, an attractive drug target for inflammatory and autoimmune disorders. Compound 14 has excellen...
  10. A selective inhibitor reveals PI3Kγ dependence of T(H)17 cell differentiation.

    Nature Chemical Biology 8(6):576 (2012) PMID 22544264

    We devised a high-throughput chemoproteomics method that enabled multiplexed screening of 16,000 compounds against native protein and lipid kinases in cell extracts. Optimization of one chemical series resulted in CZC24832, which is to our knowledge the first selective inhibitor of phosphoinosit...
  11. Diamond tips for automated electrical probing inside a scanning electron microscopy system

    Diamond and Related Materials 20(5):655 (2011)

    Pyramidal tips made from boron doped diamond have become the ultimate choice for electrically measuring semiconductor device structures in electrical atomic force microscopy (AFM). An advanced measurement setup with diamond probing units directly integrated inside a scanning electron micros...
  12. Computational prediction of proteotypic peptides for quantitative proteomics.

    Nature Biotechnology 25(1):125 (2007) PMID 17195840

    Mass spectrometry-based quantitative proteomics has become an important component of biological and clinical research. Although such analyses typically assume that a protein's peptide fragments are observed with equal likelihood, only a few so-called 'proteotypic' peptides are repeatedly and con...
  13. A proteome-wide approach identifies sumoylated substrate proteins in yeast.

    Journal of Biological Chemistry 279(40):41346 (2004) PMID 15292183

    The ubiquitin-related protein SUMO-1 is covalently attached to proteins by SUMO-1 ligases. We have performed a proteome-wide analysis of sumoylated substrate proteins in yeast. Employing the powerful affinity purification of Protein A-Smt3 (Smt3 is the yeast homologue of SUMO-1) from yeast lysat...
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