Discovery and characterization of highly potent and selective allosteric USP7 inhibitors

December 4th, 2017 by Gerald Gavory

Discovery and characterization of highly potent and selective allosteric USP7 inhibitors

Discovery and characterization of highly potent and selective allosteric USP7 inhibitors, Published online: 04 December 2017; doi:10.1038/nchembio.2528

A selective inhibitor of the deubiquitinase USP7 binds an allosteric site to inhibit its MDM2-stabilizing activity, resulting in stabilization of p53 and p21, which confers hypersensitivity to cancer cells for killing by the compound.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Discovery and characterization of highly potent and selective allosteric USP7 inhibitors

Inhibition of Delta-induced Notch signaling using fucose analogs

November 27th, 2017 by Michael Schneider

Inhibition of Delta-induced Notch signaling using fucose analogs

Inhibition of Delta-induced Notch signaling using fucose analogs, Published online: 27 November 2017; doi:10.1038/nchembio.2520

Protein O-fucosyltransferase 1 (Pofut1) regulates Notch activity by adding O-fucose residues to its extracellular domain. Fucose analogs were identified that inhibited Delta-mediated Notch binding and activation but spared Jagged1-mediated signaling.

5-Formylcytosine to cytosine conversion by C–C bond cleavage <i>in vivo</i>

November 27th, 2017 by Katharina Iwan

5-Formylcytosine to cytosine conversion by C–C bond cleavage in vivo

5-Formylcytosine to cytosine conversion by C–C bond cleavage <i>in vivo</i>, Published online: 27 November 2017; doi:10.1038/nchembio.2531

Direct conversion of 5-fdC into dC by C–C bond breakage is revealed by metabolic tracing studies through incorporation of synthetic stable isotope- and (R)-2′-fluorine-labeled dC and fdC derivatives into the genome of cultured mammalian cells.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on 5-Formylcytosine to cytosine conversion by C–C bond cleavage <i>in vivo</i>

Cancer systems biology: Harnessing off-target effects

November 21st, 2017 by Gaye Saginc

Cancer systems biology: Harnessing off-target effects

Cancer systems biology: Harnessing off-target effects, Published online: 21 November 2017; doi:10.1038/nchembio.2519

The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of action.

Host–pathogen interactions: A ubiquitin defense

November 21st, 2017 by Mirella Bucci

Host–pathogen interactions: A ubiquitin defense

Host–pathogen interactions: A ubiquitin defense, Published online: 21 November 2017; doi:10.1038/nchembio.2524

Host–pathogen interactions: A ubiquitin defense

Enzymology: I want my cluster back

November 21st, 2017 by Caitlin Deane

Enzymology: I want my cluster back

Enzymology: I want my cluster back, Published online: 21 November 2017; doi:10.1038/nchembio.2525

Enzymology: I want my cluster back

Peptide design: Hacking hemagglutinin

November 21st, 2017 by Karin Kuehnel

Peptide design: Hacking hemagglutinin

Peptide design: Hacking hemagglutinin, Published online: 21 November 2017; doi:10.1038/nchembio.2523

Peptide design: Hacking hemagglutinin

Errata: Functional annotation of chemical libraries across diverse biological processes

November 21st, 2017 by Jeff S Piotrowski

Errata: Functional annotation of chemical libraries across diverse biological processes

Errata: Functional annotation of chemical libraries across diverse biological processes, Published online: 21 November 2017; doi:10.1038/nchembio1217-1286a

Errata: Functional annotation of chemical libraries across diverse biological processes
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Errata: Functional annotation of chemical libraries across diverse biological processes

Errata: Functional annotation of chemical libraries across diverse biological processes

November 21st, 2017 by Jeff S Piotrowski

Errata: Functional annotation of chemical libraries across diverse biological processes

Errata: Functional annotation of chemical libraries across diverse biological processes, Published online: 21 November 2017; doi:10.1038/nchembio1217-1286b

Errata: Functional annotation of chemical libraries across diverse biological processes
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Errata: Functional annotation of chemical libraries across diverse biological processes

Genetic code expansion: Synthetases pick up the PACE

November 21st, 2017 by Jeffery M Tharp

Genetic code expansion: Synthetases pick up the PACE

Genetic code expansion: Synthetases pick up the PACE, Published online: 21 November 2017; doi:10.1038/nchembio.2516

Phage-assisted evolution can rapidly improve the efficiency and substrate specificity of orthogonal aminoacyl-tRNA synthetases. Furthermore, the crystal structure of the pyrrolysyl-tRNA synthetase N-terminal domain reveals the basis for these improvements and provides a structural rationale for orthogonality.