1. Catalytic in vivo protein knockdown by small-molecule PROTACs.

    Nature Chemical Biology 11(8):611 (2015) PMID 26075522

    The current predominant therapeutic paradigm is based on maximizing drug-receptor occupancy to achieve clinical benefit. This strategy, however, generally requires excessive drug concentrations to ensure sufficient occupancy, often leading to adverse side effects. Here, we describe major improve...
  2. Ion Mobility Tandem Mass Spectrometry Enhances Performance of Bottom-up Proteomics.

    Molecular & Cellular Proteomics 13(12):3709 (2014) PMID 25106551 PMCID PMC4256517

    One of the limiting factors in determining the sensitivity of tandem mass spectrometry using hybrid quadrupole orthogonal acceleration time-of-flight instruments is the duty cycle of the orthogonal ion injection system. As a consequence, only a fraction of the generated fragment ion beam is coll...
  3. Ion mobility tandem mass spectrometry enhances performance of bottom-up proteomics.

    Molecular & Cellular Proteomics 13(12):3709 (2014) PMID 25106551 PMCID PMC4256517

    One of the limiting factors in determining the sensitivity of tandem mass spectrometry using hybrid quadrupole orthogonal acceleration time-of-flight instruments is the duty cycle of the orthogonal ion injection system. As a consequence, only a fraction of the generated fragment ion beam is coll...
  4. Ion mobility tandem mass spectrometry enhances performance of bottom-up proteomics.

    Molecular & Cellular Proteomics 13(12):3709 (2014) PMID 25106551 PMCID PMC4256517

    One of the limiting factors in determining the sensitivity of tandem mass spectrometry using hybrid quadrupole orthogonal acceleration time-of-flight instruments is the duty cycle of the orthogonal ion injection system. As a consequence, only a fraction of the generated fragment ion beam is coll...
  5. Proteomics. Tracking cancer drugs in living cells by thermal profiling of the proteome.

    Science 346(6205):1255784 (2014) PMID 25278616

    The thermal stability of proteins can be used to assess ligand binding in living cells. We have generalized this concept by determining the thermal profiles of more than 7000 proteins in human cells by means of mass spectrometry. Monitoring the effects of small-molecule ligands on the profiles d...
  6. Tracking cancer drugs in living cells by thermal profiling of the proteome.

    Science 346(6205):1255784 (2014) PMID 25278616

    The thermal stability of proteins can be used to assess ligand binding in living cells. We have generalized this concept by determining the thermal profiles of more than 7000 proteins in human cells by means of mass spectrometry. Monitoring the effects of small-molecule ligands on the profiles d...
  7. Kruidenier et al. reply.

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

  8. Kruidenier et al. reply.

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

  9. Kruidenier et al. reply.

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

  10. Chemoproteomics reveals time-dependent binding of histone deacetylase inhibitors to endogenous repressor complexes.

    ACS Chemical Biology 9(8):1736 (2014) PMID 24877719

    Class I histone deacetylases (HDACs) are attractive drug targets in oncology and inflammation. However, the development of selective inhibitors is complicated by the characteristic that the localization, activity, and selectivity of class I HDACs are regulated by association in megadalton repres...
  11. Chemoproteomics reveals time-dependent binding of histone deacetylase inhibitors to endogenous repressor complexes.

    ACS Chemical Biology 9(8):1736 (2014) PMID 24877719

    Class I histone deacetylases (HDACs) are attractive drug targets in oncology and inflammation. However, the development of selective inhibitors is complicated by the characteristic that the localization, activity, and selectivity of class I HDACs are regulated by association in megadalton repres...
  12. Mass-spectrometry-based draft of the human proteome.

    Nature 509(7502):582 (2014) PMID 24870543

    Proteomes are characterized by large protein-abundance differences, cell-type- and time-dependent expression patterns and post-translational modifications, all of which carry biological information that is not accessible by genomics or transcriptomics. Here we present a mass-spectrometry-based d...
  13. Mass-spectrometry-based draft of the human proteome.

    Nature 509(7502):582 (2014) PMID 24870543

    Proteomes are characterized by large protein-abundance differences, cell-type- and time-dependent expression patterns and post-translational modifications, all of which carry biological information that is not accessible by genomics or transcriptomics. Here we present a mass-spectrometry-based d...
  14. 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...
  15. 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...
  16. 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...
  17. 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...
  18. Quantifying small molecule-induced changes in cellular protein expression and posttranslational modifications using isobaric mass tags.

    Methods in Molecular Biology 1156:431 (2014) PMID 24792006

    Proteomics enables the comprehensive analysis of cellular perturbations induced by bioactive small molecules and contributes to our understanding of the mechanisms by which drugs elicit their activity in disease situations. Here we describe a quantitative proteomics approach to study dose-depend...
  19. Mapping protein complexes using covalently linked antibodies and isobaric mass tags.

    Methods in Molecular Biology 1156:279 (2014) PMID 24791996

    Affinity enrichment techniques in combination with quantitative proteomics enable the unbiased identification of protein-protein interaction, and thus the delineation of protein complexes and interaction networks. Here, we describe an immunoaffinity enrichment approach that employs covalently im...
  20. Quantifying small molecule-induced changes in cellular protein expression and posttranslational modifications using isobaric mass tags.

    Methods in Molecular Biology 1156:431 (2014) PMID 24792006

    Proteomics enables the comprehensive analysis of cellular perturbations induced by bioactive small molecules and contributes to our understanding of the mechanisms by which drugs elicit their activity in disease situations. Here we describe a quantitative proteomics approach to study dose-depend...