ChemBioChem

Cover image for ChemBioChem

August 16, 2011

Volume 12, Issue 12

Pages 1785–1939

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireviews
    7. Communications
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    1. Cover Picture: Peptide-Functionalized Luminescent Iridium Complexes for Lifetime Imaging of CXCR4 Expression (ChemBioChem 12/2011) (page 1785)

      Dr. Joeri Kuil, Dr. Peter Steunenberg, Dr. Patrick T. K. Chin, Joppe Oldenburg, Dr. Kees Jalink, Dr. Aldrik H. Velders and Dr. Fijs W. B. van Leeuwen

      Article first published online: 5 AUG 2011 | DOI: 10.1002/cbic.201190053

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      The cover picture shows a model of a luminescent iridium(III) complex functionalized with three Ac-TZ14011 peptide moieties binding to the chemokine receptor 4 (CXCR4). The G protein-coupled receptor CXCR4 is over-expressed in many types of cancer and, therefore, is a potential biomarker in the field of diagnostic oncology. In the CPK model, the three Ac-TZ14011 peptides are colored by element and the iridium complex is red. The iridium complex has a luminescence lifetime in the order of 200 ns; this enables visualization with fluorescence lifetime imaging microscopy (FLIM). The FLIM image of cells incubated with the peptide–iridium conjugate in the background shows accumulation in the cell membranes; this is in accordance with the membrane location of CXCR4. For further information, see the communication by A. H. Velders, F. W. B. van Leeuwen, et al. on p. 1897 ff.

  2. Inside Cover

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    3. Inside Cover
    4. Graphical Abstract
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    1. Inside Cover: An MD2 Hot-Spot-Mimicking Peptide that Suppresses TLR4-Mediated Inflammatory Response in vitro and in vivo (ChemBioChem 12/2011) (page 1786)

      Liping Liu, Dr. Nilanjan Ghosh, Peter F. Slivka, Zeno Fiorini, Dr. Mark R. Hutchinson, Prof. Dr. Linda R. Watkins and Prof. Dr. Hang Yin

      Article first published online: 5 AUG 2011 | DOI: 10.1002/cbic.201190054

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      The inside cover picture shows a rationally designed MD2 hot-spot-mimicking peptide in complex with toll-like receptor 4, which is an important cell-surface receptor that plays critical roles in the innate immune system and in inflammation response. For further details on the binding affinity and specificity of this truncated peptide, see the paper by H. Yin et al. on p. 1827 ff.

  3. Graphical Abstract

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    4. Graphical Abstract
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    1. Graphical Abstract: ChemBioChem 12/2011 (pages 1787–1794)

      Article first published online: 5 AUG 2011 | DOI: 10.1002/cbic.201190055

  4. News

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  5. Minireviews

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    1. An Evaluation of Peptide-Bond Isosteres (pages 1801–1807)

      Amit Choudhary and Prof. Ronald T. Raines

      Article first published online: 12 JUL 2011 | DOI: 10.1002/cbic.201100272

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      Not better, just different: The electronic, structural, and conformational attributes of four peptide-bond isosteres—thioamides, esters, alkenes, and fluoroalkenes—can enable chemical biologists to probe structure–function relationships of peptides and proteins with unprecedented precision.

    2. Ion-Channel Modulators: More Diversity Than Previously Thought (pages 1808–1812)

      Dr. Sébastien Dilly, Cédric Lamy, Neil V. Marrion, Jean-François Liégeois and Vincent Seutin

      Article first published online: 1 JUL 2011 | DOI: 10.1002/cbic.201100236

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      Channel news: Recent studies on various ion channels have shown that allosteric modulation is an important mechanism for affecting channel function; this indicates that the action of channel modulators is more diverse than initially thought. For example, in SK channels, the “allosteric modulator” apamin was proposed to prevent conduction by binding to the rim of the outer pore (see figure).

  6. Communications

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    1. Generating DNA Synbodies from Previously Discovered Peptides (pages 1813–1817)

      Rui Liu, Bing Jiang, Hanyang Yu and Prof. John C. Chaput

      Article first published online: 20 JUN 2011 | DOI: 10.1002/cbic.201100284

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      Synbody building: We demonstrate how off-the-shelf peptides can be transformed into high affinity protein capture reagents that mimic the recognition properties of natural antibodies (see figure). The designer synthetic antibody amplifies the binding affinity of the individual peptides by ∼1000-fold to bind Grb2 with a Kd of 2 nM, and functions with high selectivity in conventional pull-down assays from HeLa cell lysates.

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      Subcellular Protein Localization by Using a Genetically Encoded Fluorescent Amino Acid (pages 1818–1821)

      Dr. Godefroid Charbon, Dr. Eric Brustad, Kevin A. Scott, Prof. Dr. Jiangyun Wang, Prof. Dr. Anders Løbner-Olesen, Prof. Dr. Peter G. Schultz, Prof. Dr. Christine Jacobs-Wagner and Prof. Dr. Eli Chapman

      Article first published online: 16 JUN 2011 | DOI: 10.1002/cbic.201100282

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      CouAA-lescence: A fluorescent amino acid (CouAA) was site-specifically incorporated into FtsZ, the bacterial tubulin homologue, in living cells. FtsZCouAA is seen at the cleavage furrow during cell division to form the Z-ring. These studies provide the first example of a fully functional protein to be visualized in vivo by using a genetically incorporated fluorescent amino acid.

    3. Hydration is Required in DNA G-Quadruplex–Protein Binding (pages 1822–1826)

      Dr. Satoru Nagatoishi, Noburu Isono, Prof. Dr. Kouhei Tsumoto and Prof. Dr. Naoki Sugimoto

      Article first published online: 10 JUN 2011 | DOI: 10.1002/cbic.201100264

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      Taking on water: The thermodynamics of G-quadruplex–protein binding were investigated for a thrombin-binding DNA aptamer (TBA) and thrombin under the molecular crowding condition of PEG 200. The binding affinity of the TBA–thrombin interaction decreased with a increasing PEG 200 concentration that decreased the water activity. This work suggests that water molecules are taken up during G-quadruplex–protein binding.

    4. An MD2 Hot-Spot-Mimicking Peptide that Suppresses TLR4-Mediated Inflammatory Response in vitro and in vivo (pages 1827–1831)

      Liping Liu, Dr. Nilanjan Ghosh, Peter F. Slivka, Zeno Fiorini, Dr. Mark R. Hutchinson, Prof. Dr. Linda R. Watkins and Prof. Dr. Hang Yin

      Article first published online: 15 JUN 2011 | DOI: 10.1002/cbic.201100211

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      Pain relief in a trunc: A truncated peptide was shown to retain the structure of the TLR4-binding hot-spot region of MD2 and to disrupt TLR4–MD2 interactions. The peptide not only demonstrated strong binding affinity in a fluorescence-polarization assay, but also showed high specificity in macrophages. Furthermore, MD2-I was able to suppress neuropathic pain in animal models.

    5. A Ribonucleotide Reductase-Like Electron Transfer System in the Nitroaryl-Forming N-Oxygenase AurF (pages 1832–1835)

      Alexander Fries, Tom Bretschneider, Dr. Robert Winkler and Prof. Dr. Christian Hertweck

      Article first published online: 15 JUN 2011 | DOI: 10.1002/cbic.201100138

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      Nitro, electrons, and RNR. Through structure comparisons, mutagenesis, and modeling we deduced that the unusual nitro-synthase AurF docks to ferredoxin and transfers electrons from the surface to the active site across hydrogen bonds in analogy to ribonucleotide reductases (RNRs). Recruitment of RNR electron-transfer components could rationalize the successful in vivo reconstitution of AurF in different expression hosts and its growth-phase-dependent activity.

    6. Two Induced Fungal Polyketide Pathways Converge into Antiproliferative Spiroanthrones (pages 1836–1839)

      Dr. Kirstin Scherlach, Anindita Sarkar, Dr. Volker Schroeckh, Dr. Hans-Martin Dahse, Dr. Martin Roth, Prof. Dr. Axel A. Brakhage, Dr. Uwe Horn and Prof. Dr. Christian Hertweck

      Article first published online: 22 JUN 2011 | DOI: 10.1002/cbic.201100132

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      Unite in times of deprivation: We report on the use of a chemostat to elicit cryptic biosynthetic pathways in a fungus. Cutlivation of Aspergillus nidulans under N-limiting conditions in a chemostat led to the specific induction of polyketide biosynthesis genes that were otherwise silent. The merger of an anthraquinone with an orsellinic acid-derived oxanthrene yielded two spiroanthrones, sanghaspirodins A and B (see figure).

    7. N-Sulfanylethylanilide Peptide as a Crypto-Thioester Peptide (pages 1840–1844)

      Kohei Sato, Prof. Dr. Akira Shigenaga, Kohei Tsuji, Shugo Tsuda, Yoshitake Sumikawa, Ken Sakamoto and Prof. Dr. Akira Otaka

      Article first published online: 7 JUL 2011 | DOI: 10.1002/cbic.201100241

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      Native chemical ligation:N-sulfanylethylanilide (SEAlide) peptides act as thioester peptides in the presence of N-terminal cysteinyl peptides and an appropriate choice of salts. With the use of the SEAlide peptide, a kinetically controlled native chemical ligation proceeding in an unprecedented highly selective manner was achieved. Additionally, a one-pot, four-component coupling under kinetic conditions was achieved.

    8. Enhanced Refoldability and Thermoactivity of Fluorinated Phosphotriesterase (pages 1845–1848)

      Peter James Baker and Prof. Jin Kim Montclare

      Article first published online: 27 JUN 2011 | DOI: 10.1002/cbic.201100221

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      Teflon-like globular proteins: Global incorporation of p-fluorophenylalanine (pFF) in the S phosphotriesterase dimer (see figure) was found to stabilize the protein and led to refoldability and improved activity for substrates at elevated temperatures.

    9. Discovery of a Metagenome-Derived Enzyme that Produces Branched-Chain Acyl-(Acyl-Carrier-Protein)s from Branched-Chain α-Keto Acids (pages 1849–1853)

      Jeffrey W. Craig and Prof. Dr. Sean F. Brady

      Article first published online: 28 JUN 2011 | DOI: 10.1002/cbic.201100215

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      A single enzyme (NasB), isolated from a soil metagenomic library, can convert branched-chain α-keto acids into branched-chain acyl-ACPs. These intermediates then enter the type-II fatty acid synthase system, yielding branched long-chain acyl-ACP substrates that are used in the biosynthesis of branched long-chain N-acyl amino acids.

    10. Probing Protein–Protein Interactions with a Genetically Encoded Photo-crosslinking Amino Acid (pages 1854–1857)

      Dr. Hui-wang Ai, Dr. Weijun Shen, Dr. Amit Sagi, Dr. Peng R. Chen and Prof. Dr. Peter G. Schultz

      Article first published online: 15 JUN 2011 | DOI: 10.1002/cbic.201100194

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      A pyrrolysyl tRNA/tRNA sythetase pair has been evolved that efficiently incorporates an aliphatic diazirine amino acid into proteins in E. coli and mammalian cells. When site-specifically introduced into the active site of Cdk5, this unnatural amino acid was able to photo-crosslink the kinase to its substrate, Pak1.

  7. Full Papers

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireviews
    7. Communications
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    1. Mechanistically Distinct Nonribosomal Peptide Synthetases Assemble the Structurally Related Antibiotics Viomycin and Capreomycin (pages 1859–1867)

      Dr. Elizabeth A. Felnagle, Angela M. Podevels, John J. Barkei and Prof. Michael G. Thomas

      Article first published online: 7 JUL 2011 | DOI: 10.1002/cbic.201100193

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      Tuberactinomycin biosynthesis: Viomycin and capreomycin are structurally related antituberculosis drugs. Analysis of the nonribosomal peptide synthetases that assemble these molecules determined that peptide assembly occurs by distinct mechanisms. These unexpected differences provide insights into how modifications to homologous nonribosomal peptide synthetases can result in structure diversification.

    2. Iminodipropionic Acid as the Leaving Group for DNA Polymerization by HIV-1 Reverse Transcriptase (pages 1868–1880)

      Xiao-Ping Song, Dr. Camille Bouillon, Prof. Dr. Eveline Lescrinier and Prof. Dr. Piet Herdewijn

      Article first published online: 28 JUN 2011 | DOI: 10.1002/cbic.201100160

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      Pyrophosphate mimics: Iminodiacetic acid phosphoramidates of deoxyadenosine monophosphate analogues, either bearing an extended aliphatic chain in the amino acid function or a phosphonic acid moiety, serve as potential substrates for HIV-1 reverse transcriptase. Iminodipropionic acid was found to be an excellent mimic of the pyrophosphate.

    3. Isopenicillin N Synthase Binds δ-(L-α-Aminoadipoyl)-L-Cysteinyl-D-Thia-allo-Isoleucine through both Sulfur Atoms (pages 1881–1885)

      Dr. Ian J. Clifton, Dr. Wei Ge, Dr. Robert M. Adlington, Prof. Sir Jack E. Baldwin and Dr. Peter J. Rutledge

      Article first published online: 15 JUN 2011 | DOI: 10.1002/cbic.201100149

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      Polar opposites: IPNS converts a wide range of substrate analogues into modified β-lactams, including nurmerous tripeptides in which the third amino acid (normally valine) is substituted. However IPNS does not like polar residues in this position. The crystal structure of the protein with a substrate analogue that incorporates D-thio-allo-isoleucine in place of valine sheds light on this predilection.

    4. Revisiting the Mechanism of the Triosephosphate Isomerase Reaction: The Role of the Fully Conserved Glutamic Acid 97 Residue (pages 1886–1896)

      Moumita Samanta, M. R. N. Murthy, Hemalatha Balaram and Prof. Padmanabhan Balaram

      Article first published online: 10 JUN 2011 | DOI: 10.1002/cbic.201100116

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      The critical role of the fully conserved glutamic acid 97 (E97) residue in the triosephosphate isomerase proton transfer cycle has been demonstrated by structural and kinetic studies of the E97Q and E97D mutants of the enzyme from Plasmodium falciparum.

    5. Peptide-Functionalized Luminescent Iridium Complexes for Lifetime Imaging of CXCR4 Expression (pages 1897–1903)

      Dr. Joeri Kuil, Dr. Peter Steunenberg, Dr. Patrick T. K. Chin, Joppe Oldenburg, Dr. Kees Jalink, Dr. Aldrik H. Velders and Dr. Fijs W. B. van Leeuwen

      Article first published online: 7 JUL 2011 | DOI: 10.1002/cbic.201100271

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      FLIM festival: The chemokine receptor 4 (CXCR4) is over-expressed in 23 types of cancer. Different numbers of an antagonistic CXCR4-targeting peptide have been conjugated to luminescent iridium complexes. We have found that these conjugates are able bind CXCR4 with high affinity (see figure), and can be used in fluorescence lifetime imaging microscopy (FLIM) experiments.

    6. Synthesis and Structural Characterization of 2′-Fluoro-α-L-RNA-Modified Oligonucleotides (pages 1904–1911)

      Dr. Troels Bundgaard Jensen, Dr. Anna Pasternak, Dr. Andreas Stahl Madsen, Dr. Michael Petersen and Prof. Jesper Wengel

      Article first published online: 4 JUL 2011 | DOI: 10.1002/cbic.201100161

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      Conformational tuning: We have studied the novel 2′-F-α-L-RNA monomer as a potential monocyclic mimic of the bicyclic α-L-LNA (see figure). The two nucleotide analogues are conformationally similar but with respect to duplex stability the α-L-LNA monomer outcompetes 2′-F-α-L-RNA.

    7. Strain-Promoted Alkyne–Azide Cycloadditions (SPAAC) Reveal New Features of Glycoconjugate Biosynthesis (pages 1912–1921)

      Ngalle Eric Mbua, Dr. Jun Guo, Dr. Margreet A. Wolfert, Prof. Dr. Richard Steet and Prof. Dr. Geert-Jan Boons

      Article first published online: 9 JUN 2011 | DOI: 10.1002/cbic.201100117

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      SPAAC-ed out: A range of new reagents has been developed for strain-promoted azide–alkyne cycloadditions (SPAAC). These were employed in combination with metabolic labeling and traditional lectin staining to examine defective glycoprotein glycosylation in cells. The fidelity of Golgi trafficking and the quantity of sugar nucleotides were found to be critical parameters for the types of oligosaccharides that are biosynthesized.

    8. Label-Free Nondestructive Discrimination of Colon Carcinoma Sublines and Biomolecular Insights into their Differential Hsp70 Expression: DNA/RNA Nucleobase Specific Changes (pages 1922–1936)

      Dr. Patrice Donfack, Prof. Dr. Gabriele Multhoff and Prof. Dr. Arnulf Materny

      Article first published online: 7 JUL 2011 | DOI: 10.1002/cbic.201000653

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      Split screen: The picture shows colon carcinoma CX2 line expansion into the sublines CX/CX+ due to their specifically different Hsp70 expression patterns. Only immunofluorescence helps to quantify Hsp70 in order to FACS-sort the cells. Yet, Raman fingerprints of CX/CX+ not only hold potential for label-free nondestructive cell sorting, but could also provide insights into nucleobase changes attributed to alterations in DNA binding interactions.

  8. Preview

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireviews
    7. Communications
    8. Full Papers
    9. Preview
    1. You have free access to this content
      Preview: ChemBioChem 13/2011 (page 1939)

      Article first published online: 5 AUG 2011 | DOI: 10.1002/cbic.201190057

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