Discovery of Peptoid Ligands for Anti-Aquaporin 4 Antibodies

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Highlights? Peptoid ligands for anti-AQP4 autoantibodies that drive NMO have been identified ? Some of these peptoids provide an accurate blood test for the disease     

Firefly luciferase in chemical biology: a compendium of inhibitors, mechanistic evaluation of chemotypes, and suggested use as a reporter

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Highlights? A representative small molecule library contains 12% firefly luciferase inhibitors ? Competitive, noncompetitive, uncompetitive, and MAI inhibitors were identified ? For FLuc-RGAs 65% of FLuc inhibitors with known MOIs increased the luminescence signal ? Methods to identify FLuc inhibitors that interfere with assay results are described     

Rational design of an aryl-C-glycoside catalyst from a natural product O-glycosyltransferase

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Highlights? 106 rationally designed chimeras were expressed in vivo and screened by HPLC-MS analysis ? One 12-amino acid protein segment is crucial for O- or C-glycosylation ? The sugar-acceptor postioning determines O- or C-glycosidic bond formation ? Ala substitutions revealed the key spots for glycosylation     

The Antimalarial Natural Product Symplostatin 4 Is a Nanomolar Inhibitor of the Food Vacuole Falcipains

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Highlights? A convergent chemical synthesis of symplostatin 4 (Sym4) and Sym4 derivatives is reported ? Sym4 irreversibly inhibits malarial falcipains in infected red blood cells ? Sym4's unusual methyl-methoxypyrrolinone group is required for nanomolar inhibition of falcipains     

A Synthetic Substrate of DNA Polymerase Deviating from the Bases,Sugar, and Leaving Group of Canonical Deoxynucleoside Triphosphates

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Highlights? A highly modified nucleotide as substrate for polymerases ? The reversibility of the polymerase reaction at the template level ? Synthesis of a nucleoside with two anomeric centers     

HTS by NMR of Combinatorial Libraries: A Fragment-Based Approach to Ligand Discovery

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Highlights? HTS by NMR combines protein NMR and combinatorial chemistry to screen large libraries ? The approach is best suited to identify ligands to protein-protein interactions ? The method enables a rapid assessment of the druggability of a given target ? We applied the method to a test case and to derive potent and selective EphA4 ligands     

Regulation of Telomere Length by G-Quadruplex Telomere DNA- and TERRA-Binding Protein TLS/FUS

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Highlights? TLS/FUS is identified as a G-quadruplex telomere DNA and TERRA-binding protein ? TLS binds to G-quadruplex telomere DNA and TERRA simultaneously ? The cells overexpressing TLS show gradual and progressive telomere shortening ? Overexpression of TLS results in trimethylation of histone H3 and H4 at telomere     

Identification of exosite-targeting inhibitors of anthrax lethal factor by high-throughput screening

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Highlights? Development of an assay for LF protease using a full-length protein substrate ? Lichen depsidones identified as exosite-targeting LF inhibitors ? Exosite inhibitors protect macrophages from LF cytotoxicity     

Fluorescence Imaging of Single-Copy DNA Sequences within the Human Genome Using PNA-Directed Padlock Probe Assembly

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Highlights? PNA-directed assembly of the labeling complex on duplex DNA ? Padlock probes combined with rolling circle amplification for signal amplification ? Multitarget visualization within the human genome with high sequence selectivity     

Reconstitution of Nucleosome Demethylation and Catalytic Properties of a Jumonji Histone Demethylase

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Highlights? Catalytic domain of JMJD2A (cJMJD2A) removes methyl marks in a distributive manner ? Homogeneously methylated nucleosomes were used as substrates ? Quantitative assay for nucleosome demethylation has been developed     

Structural and functional investigation of the intermolecular interaction between NRPS adenylation and carrier protein domains

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Highlights? Crystallographic structure of NRPS adenylation and PCP domain interface ? NRPS adenylation C-terminal domain rotation creates appropriate PCP interface ? Mechanism-based inhibitor traps conformationally flexible proteins ? Structure-guided mutagenesis improves noncognate NRPS interactions     

Morphobase,an Encyclopedic Cell Morphology Database,and Its Use for Drug Target Identification

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Highlights? Development of an encyclopedia of cell morphology, Morphobase ? Small molecules classified by mode of action with Morphobase ? Morphobase system rapidly predicts molecular targets of compounds ? NPD6689 targets tubulin and is a lead for a class of antitubulin drugs     

Chemical Proteomics with Sulfonyl Fluoride Probes Reveals Selective Labeling of Functional Tyrosines in Glutathione Transferases

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Highlights? Sulfonyl fluoride probes label diverse GSTs in both plant and mouse proteomes ? GSTs are labeled on Tyr residues in unconserved substrate binding pockets ? Labeled Tyr residues are essential for GST function     

Interplay between the Ribosomal Tunnel,Nascent Chain,and Macrolides Influences Drug Inhibition

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Highlights? Macrolides exhibit nascent polypeptide chain–dependent inhibition ? Peptides can form specific interactions with the ribosomal tunnel ? A covalent bond between tylosin and the ribosome is necessary for inhibitory activity     

A LOV2 Domain-Based Optogenetic Tool to Control Protein Degradation and Cellular Function

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Highlights? Optogenetic tool to control the stability of soluble and membrane proteins ? Engineered using the LOV2 domain and a murine ornithine decarboxylase-like degron ? Creation of light-switchable, conditional mutants ? Graded response to very low blue light intensities allows yeast photography     

Picoliter cell lysate assays in microfluidic droplet compartments for directed enzyme evolution

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Highlights? Microfluidic droplet compartments miniaturize cell lysate screening assays ? Picoliter single-cell lysate assays comparable in sensitivity to macroscale ? Directed evolution results in improved clones validating this experimental set-up ? Precision of droplet sorting enables enrichment of clones with slight improvements     

Terpendole E,a Kinesin Eg5 Inhibitor,Is a Key Biosynthetic Intermediate of Indole-Diterpenes in the Producing Fungus Chaunopycnis alba

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Highlights? The terpendole biosynthetic gene cluster was isolated ? Terpendole E is a key biosynthetic intermediate of indole-diterpenes ? Terpendole E was overproduced by gene knockout of the bispecific enzyme TerP ? Indole-diterpene biosynthetic pathways can be classified into two groups     

A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase

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Highlights? Growth arrest induced by human telomerase in yeast is chemically reversible ? Readout is sensitive to telomerase catalytic activity and telomere recruitment ? Three cell-permeable compounds also inhibit purified human telomerase ? Yeast can be successfully used to screen for human telomerase inhibitors     

Biomembrane interactions reveal the mechanism of action of surface-immobilized host defense IDR-1010 peptide

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Highlights? Biomembrane interactions of surface-tethered host defense peptides are studied ? Polymer brush-tethered IDR-1010cys showed enhanced biomembrane interactions ? Mechanism of action of surface-tethered peptides is different from its soluble form     

Targeted Single-Cell Microchemical Analysis: MS-Based Peptidomics of Individual Paraformaldehyde-Fixed and Immunolabeled Neurons

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Highlights? Investigation of archived biological tissue at the single-cell level ? Screening of neuropeptides from immunolabeled tissue preserved up to 42 weeks ? Validation of antibody specificity using mass spectrometric approaches ? Standardized protocols for comprehensive characterization of selected cells