1. Interrogating the Druggability of the 2-Oxoglutarate-Dependent Dioxygenase Target Class by Chemical Proteomics.

    ACS Chemical Biology 11(7):2002 (2016) PMID 27197014

    The 2-oxoglutarate-dependent dioxygenase target class comprises around 60 enzymes including several subfamilies with relevance to human disease, such as the prolyl hydroxylases and the Jumonji-type lysine demethylases. Current drug discovery approaches are largely based on small molecule inhibit...
  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. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.

    Nature Chemical Biology 11(3):189 (2015) PMID 25622091 PMCID PMC4397581

    PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of huma...
  4. Kruidenier et al. reply.

    Nature 514(7520):E2 (2014) PMID 25279927

  5. Chemical proteomic analysis reveals the drugability of the kinome of Trypanosoma brucei.

    ACS Chemical Biology 7(11):1858 (2012) PMID 22908928 PMCID PMC3621575

    The protozoan parasite Trypanosoma brucei is the causative agent of African sleeping sickness, and there is an urgent unmet need for improved treatments. Parasite protein kinases are attractive drug targets, provided that the host and parasite kinomes are sufficiently divergent to allow specific...
  6. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response.

    Nature 488(7411):404 (2012) PMID 22842901 PMCID PMC4691848

    The jumonji (JMJ) family of histone demethylases are Fe2+- and α-ketoglutarate-dependent oxygenases that are essential components of regulatory transcriptional chromatin complexes. These enzymes demethylate lysine residues in histones in a methylation-state and sequence-specific context. Conside...
  7. Determination of kinase inhibitor potencies in cell extracts by competition binding assays and isobaric mass tags.

    Methods in Molecular Biology 803:141 (2012) PMID 22065223

    Chemical proteomics offers a unique approach for target identification of small molecule inhibitors directly from cell extracts, thus enabling characterization of target proteins under close to physiological conditions. Here, we describe a competition binding procedure that is based on affinity ...
  8. Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes.

    Nature Biotechnology 29(3):255 (2011) PMID 21258344

    The development of selective histone deacetylase (HDAC) inhibitors with anti-cancer and anti-inflammatory properties remains challenging in large part owing to the difficulty of probing the interaction of small molecules with megadalton protein complexes. A combination of affinity capture and qu...
  9. Robust and sensitive iTRAQ quantification on an LTQ Orbitrap mass spectrometer.

    Molecular & Cellular Proteomics 7(9):1702 (2008) PMID 18511480 PMCID PMC2556025

    Isobaric stable isotope tagging reagents such as tandem mass tags or isobaric tags for relative and absolute quantification enable multiplexed quantification of peptides via reporter ion signals in the low mass range of tandem mass spectra. Until recently, the poor recovery of low mass fragments...
  10. Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors.

    Nature Biotechnology 25(9):1035 (2007) PMID 17721511

    We describe a chemical proteomics approach to profile the interaction of small molecules with hundreds of endogenously expressed protein kinases and purine-binding proteins. This subproteome is captured by immobilized nonselective kinase inhibitors (kinobeads), and the bound proteins are quantif...
  11. Proton conductivity study of a fuel cell membrane with nanoscale resolution.

    ChemPhysChem 8(4):519 (2007) PMID 17274094

  12. Gbx2 and Otx2 interact with the WD40 domain of Groucho/Tle corepressors.

    Molecular and Cellular Biology 27(1):340 (2007) PMID 17060451 PMCID PMC1800652

    One of the earliest organizational decisions in the development of the vertebrate brain is the division of the neural plate into Otx2-positive anterior and Gbx2-positive posterior territories. At the junction of these two expression domains, a local signaling center is formed, known as the midbr...
  13. Corecruitment of the Grg4 repressor by PU.1 is critical for Pax5-mediated repression of B-cell-specific genes.

    EMBO Reports 5(3):291 (2004) PMID 14993928 PMCID PMC1299001

    PU.1 and Pax5 are important regulators of immunoglobulin heavy-chain (IgH) gene expression in B lineage cells. We have previously shown that PU.1 can potentiate the transcription of an IgH HS1,2 enhancer-linked reporter gene, and that Pax5 represses the same enhancer in transient transfection as...
  14. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.

    Nature Cell Biology 6(2):97 (2004) PMID 14743216

    Signal transduction pathways are modular composites of functionally interdependent sets of proteins that act in a coordinated fashion to transform environmental information into a phenotypic response. The pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha triggers a signalling cascade,...