Resistance mechanisms: Watering down a warhead

December 12th, 2017 by Caitlin Deane

Resistance mechanisms: Watering down a warhead

Resistance mechanisms: Watering down a warhead, Published online: 12 December 2017; doi:10.1038/nchembio.2542

Resistance mechanisms: Watering down a warhead

Protein engineering: Finding the best ligase

December 12th, 2017 by Christian F W Becker

Protein engineering: Finding the best ligase

Protein engineering: Finding the best ligase, Published online: 12 December 2017; doi:10.1038/nchembio.2533

Modification of folded proteins at will, within any sequence context, remains an elusive goal. A proteome-wide screening approach has now identified a set of protein ligases that enables conjugation of peptides to almost any protein N terminus, overcoming longstanding limitations in protein engineering.

Neurobiology: Defining your territory

December 12th, 2017 by Grant Miura

Neurobiology: Defining your territory

Neurobiology: Defining your territory, Published online: 12 December 2017; doi:10.1038/nchembio.2544

Neurobiology: Defining your territory

Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs

December 11th, 2017 by John D McCorvy

Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs

Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs, Published online: 11 December 2017; doi:10.1038/nchembio.2527

Development of D2 dopamine receptor ligands biased for β-arrestin recruitment based on a receptor homology model that identified conserved ligand contacts within the TM5 and EL2 regions as important for biased signaling.
  • Posted in Nat Chem Biol, Publications
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Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm

December 11th, 2017 by Matthew J Lee

Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm

Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm, Published online: 11 December 2017; doi:10.1038/nchembio.2535

Two complementary coiled-coil peptides and a bacterial microcompartment shell protein are combined to construct cytoscaffolds within Escherichia coli cells. Targeting enzymes to the cytoplasmic scaffold results in colocalization and improved metabolic flux.
  • Posted in Nat Chem Biol, Publications
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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
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Human antibody-based chemically induced dimerizers for cell therapeutic applications

December 4th, 2017 by Zachary B Hill

Human antibody-based chemically induced dimerizers for cell therapeutic applications

Human antibody-based chemically induced dimerizers for cell therapeutic applications, Published online: 04 December 2017; doi:10.1038/nchembio.2529

Selections with a phage-displayed antibody library against an existing protein–small-molecule complex enabled the generation of antibody-based chemically induced dimerizers (AbCIDs) with the properties necessary for use in regulating cell therapies.
  • Posted in Nat Chem Biol, Publications
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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
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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