ChemBioChem

Cover image for Vol. 11 Issue 18

December 10, 2010

Volume 11, Issue 18

Pages 2473–2619

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Review
    11. Preview
    1. Cover Picture: Linking Chemical and Microbial Diversity in Marine Sponges: Possible Role for Poribacteria as Producers of Methyl-Branched Fatty Acids (ChemBioChem 18/2010) (page 2473)

      Thomas Hochmuth, Holger Niederkrüger, Christine Gernert, Alexander Siegl, Dr. Stefan Taudien, Dr. Matthias Platzer, Prof. Dr. Phillip Crews, Prof. Dr. Ute Hentschel and Prof. Dr. Jörn Piel

      Version of Record online: 7 DEC 2010 | DOI: 10.1002/cbic.201090087

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      The cover picture shows the marine sponge Cacospongia mycofijiensis and some of its microbial and lipid constituents. Sponges are one of the richest sources of natural products, and many of these animals harbor massive consortia of diverse symbiotic bacteria. These symbionts are increasingly being recognized as the true source of many sponge-derived primary and secondary metabolites. In addition to cytotoxic polyketides, such as fijianolides (laulimalides), latrunculin and mycothiazol, C. mycofijiensis contains numerous highly characteristic mid-chain-branched fatty acids in its lipids. These fatty acids are generally detected in high-microbial-abundance sponges, but have not been found in sponges harboring few bacteria. Metagenomic deep sequencing of biosynthetic genes, comparative lipid analysis, and 16S rRNA studies of symbionts suggest that symbionts belonging to the sponge-specific candidate phylum “Poribacteria” might synthesize these lipids by employing unusual polyketide synthase-like enzymes. For more information see the paper by J. Piel et al. on p. 2572 ff. Illustration: Jörn Piel, Ute Hentschel, and Phillip Crews.

  2. Inside Cover

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Review
    11. Preview
    1. Inside Cover: Characterization of Irreversible Kinase Inhibitors by Directly Detecting Covalent Bond Formation: A Tool for Dissecting Kinase Drug Resistance (ChemBioChem 18/2010) (page 2474)

      Sabine Klüter , Dr. Jeffrey R. Simard , Dr. Haridas B. Rode, Dr. Christian Grütter, Dr. Vijaykumar Pawar, Dr. Hans C. A. Raaijmakers, Dr. Tjeerd A. Barf, Dr. Matthias Rabiller, Prof. Dr. Willem A. L. van Otterlo  and Dr. Daniel Rauh 

      Version of Record online: 7 DEC 2010 | DOI: 10.1002/cbic.201090088

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      The inside cover picture shows a covalent inhibitor bound to the drug resistance mutant T790M of the epidermal growth factor receptor kinase (EFGR). The inhibitor interacts with the hinge region of the kinase domain, and its electrophile modifies the side chain thiol of a cysteine residue of EGFR. For further details, see the paper by D. Rauh et al. on p. 2557 ff.

  3. Graphical Abstract

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Review
    11. Preview
  4. News

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Review
    11. Preview
  5. Minireview

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Review
    11. Preview
    1. Design and Synthesis of Antifreeze Glycoproteins and Mimics (pages 2489–2498)

      Dr. James Garner and Prof. Margaret M. Harding

      Version of Record online: 24 NOV 2010 | DOI: 10.1002/cbic.201000509

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      On ice: New synthetic routes to antifreeze glycoproteins as pure glycoforms, the identification of cyclic antifreeze glycoproteins, structure–activity studies, conformational studies and the properties of novel C-linked analogues, present opportunities for the design and synthesis of novel ice-growth-inhibiting and antifreeze compounds.

  6. Highlight

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Review
    11. Preview
    1. High-Throughput DNA Sequencing Beyond the Four-Letter Code: Epigenetic Modifications Revealed by Single-Molecule Bypass Kinetics (pages 2499–2501)

      Dr. Daniel Summerer

      Version of Record online: 19 NOV 2010 | DOI: 10.1002/cbic.201000569

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      SM(A)RT analysis: A new approach for the direct high-throughput analysis of both DNA sequence and epigenetic nucleobase modifications is reviewed. The method, which relies on single-molecule, real-time (SMRT) DNA sequencing and overcomes many of the limitations of previous technologies for detecting methylation, might allow the detection of any nucleotide modifications that affect DNA polymerase bypass kinetics. Adapted from Nat. Methods Vol. 7, p. 461 with permission. Copyright Macmillan Publishers Ltd. (2010).

  7. Communications

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Review
    11. Preview
    1. Combinatorial Alanine Substitution Enables Rapid Optimization of Cytochrome P450BM3 for Selective Hydroxylation of Large Substrates (pages 2502–2505)

      Dr. Jared C. Lewis, Simone M. Mantovani, Yu Fu, Dr. Christopher D. Snow, Russell S. Komor, Prof. Chi-Huey Wong  and Prof. Frances H. Arnold

      Version of Record online: 24 NOV 2010 | DOI: 10.1002/cbic.201000565

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      Made for each other: Combinatorial alanine substitution of active site residues in a thermostable cytochrome P450BM3 variant was used to generate an enzyme that is active with large substrates. Selective hydroxylation of methoxymethylated monosaccharides, alkaloids, and steroids was thus made possible (see Scheme). This approach could be useful for improving the activity of enzymes that show only limited activity with larger substrates.

    2. Genome Mining Reveals trans-AT Polyketide Synthase Directed Antibiotic Biosynthesis in the Bacterial Phylum Bacteroidetes (pages 2506–2512)

      Dr. Roberta Teta , Dr. Mihaela Gurgui, Eric J. N. Helfrich, Stefan Künne, Andreas Schneider, Dr. Gerhild Van Echten-Deckert, Prof. Dr. Alfonso Mangoni and Prof. Dr. Jörn Piel

      Version of Record online: 15 NOV 2010 | DOI: 10.1002/cbic.201000542

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      On target:Trans-AT polyketide synthases (PKSs) are a recently discovered group of biosynthetic enzymes present in many bacteria. A strategy for the prediction of natural product structures from trans-AT PKS sequences was demonstrated to be a useful approach for the targeted isolation of bioactive polyketides from chemically poorly studied prokaryotic phyla, as exemplified by the elansolid-type antibiotics.

    3. 2′-O-Appended Polyamines that Increase Triple-Helix-Forming Oligonucleotide Affinity are Selected by Dynamic Combinatorial Chemistry (pages 2513–2516)

      Dr. Laurent Azéma , Dr. Katell Bathany and Dr. Bernard Rayner 

      Version of Record online: 19 NOV 2010 | DOI: 10.1002/cbic.201000538

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      Stability leads to selection: Cationic appending groups on a triplex-forming oligonucleotide (TFO) designed to bind a DNA target can be rapidly selected from a small library of various amines and polyamines for their capacity to stabilize triple-helix formation.

    4. Cyclization of Synthetic seco-Proansamitocins to Ansamitocin Macrolactams by Actinosynnema pretiosum as Biocatalyst (pages 2517–2520)

      Dr. Kirsten Harmrolfs, Dr. Marco Brünjes, Dr. Gerald Dräger, Prof. Dr. Heinz G. Floss, Dr. Florenz Sasse, Dr. Florian Taft and Prof. Dr. Andreas Kirschning

      Version of Record online: 12 NOV 2010 | DOI: 10.1002/cbic.201000422

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      Ring closure is possible with seco-proansamitocin and two activated SNAC esters, which can be processed to ansamitocin P3 and 19-deschloro-20-demethoxy AP-3, respectively, by an AHBA-blocked mutant of Actinosynnema pretiosum. This work sheds light on the synthetic potential of macrolactamizing amide synthases. The new ansamitocin derivative showed similar to enhanced antiproliferative activity against several cancer cell lines relative to AP-3.

    5. Engineering Protein Sequence Composition for Folding Robustness Renders Efficient Noncanonical Amino acid Incorporations (pages 2521–2524)

      Soundrarajan Nagasundarapandian, Dr. Lars Merkel, Prof. Nediljko Budisa, Raghunathan Govindan, Dr. Niraikulam Ayyadurai, Sokalingam Sriram, Prof. Hyungdon Yun and Prof. Sun-Gu Lee

      Version of Record online: 9 NOV 2010 | DOI: 10.1002/cbic.201000380

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      Folding up: Residue-specific incorporation of noncanonical amino acids (NCAAs) often results in loss of protein function either by misfolding or aggregation (left). However, engineering the protein sequence for enhanced folding increases the mutational robustness of the protein to accommodate novel side chains and generate tailor-made proteins with new properties (right).

    6. Synthetic Peptidoglycan Motifs for Germination of Bacterial Spores (pages 2525–2529)

      Dr. Mijoon Lee, Dr. Dusan Hesek, Dr. Ishita M. Shah, Dr. Allen G. Oliver, Dr. Jonathan Dworkin and Dr. Shahriar Mobashery

      Version of Record online: 29 NOV 2010 | DOI: 10.1002/cbic.201000626

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      Spore cheat: Certain important pathogenic bacteria can produce spores, which are a dormant cell type that is able to resist and survive unfavorable conditions. Environmental factors stimulate the germination of spores and result in regeneration of the bacterium. Minimal bacterial peptidoglycan motifs, prepared herein in multistep syntheses, potently stimulated spore germination in the low-nanomolar range (see scheme).

    7. Six-Colour HyBeacon Probes for Multiplex Genetic Analysis (pages 2530–2533)

      Dr. James A. Richardson, Marta Gerowska, Montserrat Shelbourne, Dr. David French and Prof. Tom Brown

      Version of Record online: 24 NOV 2010 | DOI: 10.1002/cbic.201000623

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      A combination of six HyBeacon probes has been used in multiplex genetic analysis to analyse mutations in the CFTR gene of PCR-amplified human DNA. Multicolour HyBeacons of this type have great potential in human genetic screening and point-of-care diagnosis.

    8. Mechanism of Acetylaminofluorene-dG Induced Frameshifting by Polymerase η (pages 2534–2537)

      Stephanie Schorr and Prof. Dr. Thomas Carell

      Version of Record online: 9 NOV 2010 | DOI: 10.1002/cbic.201000579

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      Frameshift mutations: Bulky adduct DNA lesions, such as the C8-acetylaminofluorene dG lesion (AAF-dG), induce frameshift mutations if they are placed in special gene sequences. With the help of synthetic AAF-dG lesions inserted into different repetitive frameshift-prone sequences, the molecular basis of the −I, −II, and −III frameshifting events was determined.

    9. An Aptamer-Based Nanobiosensor for Real-Time Measurements of ATP Dynamics (pages 2538–2541)

      Prof. Veli C. Özalp, Lise J. Nielsen and Prof. Lars F. Olsen

      Version of Record online: 17 NOV 2010 | DOI: 10.1002/cbic.201000500

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      How ATP! A nanosensor based on a new DNA aptamer can show changes in intracellular concentration of ATP of 0.5 to 8 mM and thereby the kinetics of ATP-consuming reactions in real-time. The biosensor was protected against nuclease attack by being buried in a polyacrylamide nanoparticle. This strategy can readily be applied to any metabolite of interest in cells.

  8. Full Papers

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Review
    11. Preview
    1. myo-Inositol Trispyrophosphate: A Novel Allosteric Effector of Hemoglobin with High Permeation Selectivity across the Red Blood Cell Plasma Membrane (pages 2543–2548)

      Dr. Carolina D. Duarte , Dr. Ruth Greferath , Prof. Dr. Claude Nicolau  and Prof. Dr. Jean-Marie Lehn

      Version of Record online: 17 NOV 2010 | DOI: 10.1002/cbic.201000499

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      Blood boosting:myo-Inositol trispyrophosphate (ITPP), a novel membrane-permeant allosteric effector of hemoglobin, enhances regulated oxygen release from red blood cells (RBCs), thus counteracting the effects of hypoxia. ITPP uptake appears to be mediated by the band 3 anion carrier RBC membrane protein and is thus highly tissue-selective towards RBCs, a important feature for its potential therapeutic use.

    2. Structural Basis for the Properties of Two Single-Site Proline Mutants of CYP102A1 (P450BM3) (pages 2549–2556)

      Dr. Christopher J. C. Whitehouse , Wen Yang , Jake A. Yorke, Benjamin C. Rowlatt, Anthony J. F. Strong, Dr. Christopher F. Blanford, Dr. Stephen G. Bell, Dr. Mark Bartlam, Dr. Luet-Lok Wong and Prof. Zihe Rao 

      Version of Record online: 25 NOV 2010 | DOI: 10.1002/cbic.201000421

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      Protein evolution with proline: The crystal structures of two contrasting single-site proline mutants of CYP102A1 (P450BM3) have been solved. The two mutations combine to give a variant that shows substantially enhanced catalytic activity with small non-natural substrates (see graph).

    3. Characterization of Irreversible Kinase Inhibitors by Directly Detecting Covalent Bond Formation: A Tool for Dissecting Kinase Drug Resistance (pages 2557–2566)

      Sabine Klüter , Dr. Jeffrey R. Simard , Dr. Haridas B. Rode, Dr. Christian Grütter, Dr. Vijaykumar Pawar, Dr. Hans C. A. Raaijmakers, Dr. Tjeerd A. Barf, Dr. Matthias Rabiller, Prof. Dr. Willem A. L. van Otterlo  and Dr. Daniel Rauh 

      Version of Record online: 15 NOV 2010 | DOI: 10.1002/cbic.201000352

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      Dissecting the mechanisms of kinase drug resistance: We describe a straightforward assay system, which allowed real-time detection of irreversible kinase inhibition without requiring ATP or time-dependent IC50 measurements. This assay system provided an effective tool for dissecting drug-resistance mechanisms resulting from point mutations at the gatekeeper position.

    4. Analysis of Metal Ion Dependence in glmS Ribozyme Self-Cleavage and Coenzyme Binding (pages 2567–2571)

      Kevin Klawuhn, Joshua A. Jansen, Joshua Souchek, Prof. Garrett A. Soukup and Prof. Juliane K. Soukup

      Version of Record online: 24 NOV 2010 | DOI: 10.1002/cbic.201000544

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      Metal ions are essential to RNA structure and function. This work provides evidence that metal ion properties dictate binding and influence differences in the overall apparent pKa of the coenzyme-dependent self-cleavage reaction. The results have implications regarding alternative roles for metal ions in catalysis and impact the design of antibiotic coenzymes.

    5. Linking Chemical and Microbial Diversity in Marine Sponges: Possible Role for Poribacteria as Producers of Methyl-Branched Fatty Acids (pages 2572–2578)

      Thomas Hochmuth, Holger Niederkrüger, Christine Gernert, Alexander Siegl, Dr. Stefan Taudien, Dr. Matthias Platzer, Prof. Dr. Phillip Crews, Prof. Dr. Ute Hentschel and Prof. Dr. Jörn Piel

      Version of Record online: 12 NOV 2010 | DOI: 10.1002/cbic.201000510

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      Sponge's best friend: Uncultivated bacterial symbionts emerge as the likely source of many natural products isolated from marine sponges. A chemical, microbial, genetic, and biochemical study of 12 sponges revealed a positive correlation between bacterial and metabolic content and provide new insight into the role of bacteria in the production of sponge-derived primary and secondary metabolites.

    6. Biological Evaluation and Structural Determinants of p38α Mitogen-Activated-Protein Kinase and c-Jun-N-Terminal Kinase 3 Inhibition by Flavonoids (pages 2579–2588)

      Márcia Goettert, Verena Schattel, Dr. Pierre Koch, Prof. Dr. Irmgard Merfort and Prof. Dr. Stefan Laufer

      Version of Record online: 24 NOV 2010 | DOI: 10.1002/cbic.201000487

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      Nature made: A thorough structure–activity relationship study incorporating the natural products, flavonoids, as MAP kinase inhibitors is presented. Forty three flavonoids—aglycones and its derived glycosides—were tested for their ability to inhibit p38α MAP kinase and JNK3. Molecular modelling studies (see figure) were carried out to shed light on the binding mode of this class of compound.

    7. Towards Practical Baeyer–Villiger-Monooxygenases: Design of Cyclohexanone Monooxygenase Mutants with Enhanced Oxidative Stability (pages 2589–2596)

      Diederik J. Opperman  and Prof. Manfred T. Reetz

      Version of Record online: 15 NOV 2010 | DOI: 10.1002/cbic.201000464

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      Customizing enzymes: Combinatorial mutations of selected cysteine and methionine residues in cyclohexanone monooxygenase (CHMO) gave rise to two mutants with either oxidative or thermal stability. We propose that oxidation-stable mutants might well be a “prerequisite” for thermostabilization, because laboratory-evolved thermostability in CHMO might be masked by a high degree of oxidation instability.

    8. Incorporation of 2′-Deoxy-2′-isonucleoside 5′-Triphosphates (iNTPs) into DNA by A- and B-Family DNA Polymerases with Different Recognition Mechanisms (pages 2597–2605)

      Takaaki Ogino, Dr. Kousuke Sato and Prof. Dr. Akira Matsuda

      Version of Record online: 24 NOV 2010 | DOI: 10.1002/cbic.201000449

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      Polymerases' taste for sugar: The synthesis of 2′-deoxy-2′-isonucleoside 5′-triphosphates (iNTPs) having the four natural nucleobases and their incorporation into primer–template duplexes by using primer extension reactions were investigated. Different recognition mechanisms were also discussed between Klenow fragment (an A-family polymerase) and Therminator (a B-family polymerase) in their elongation reactions.

    9. Cationic Peptides that Increase the Thermal Stabilities of 2′-O-MeRNA/RNA Duplexes but Do Not Affect DNA/DNA Melting (pages 2606–2612)

      Dr. Merita Murtola, Dr. Simone Zaramella, Dr. Esther Yeheskiely and Prof. Roger Strömberg

      Version of Record online: 25 NOV 2010 | DOI: 10.1002/cbic.201000324

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      Helix discrimination: If a double-stranded oligonucleotide complex in solution encounters a peptide carrying multiple opposite charges, it appears far from obvious that this will necessarily have a positive effect upon the thermal stability of the complex. Fascinatingly, though, these relatively flexible short peptides discriminate between affecting DNA/DNA B-type helices and 2′-O-MeRNA/RNA A-type duplexes.

  9. Book Review

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Review
    11. Preview
    1. The Chemical Biology of Nucleic Acids. Edited by Günter Mayer. (page 2613)

      Keith R. Fox

      Version of Record online: 19 NOV 2010 | DOI: 10.1002/cbic.201000661

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      Wiley, Hoboken 2010, XIII+464 pp., hardcover $ 170.00.—ISBN 978-0-470-51974-5

  10. Preview

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Minireview
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Review
    11. Preview
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      Preview: ChemBioChem 1/2011 (page 2619)

      Version of Record online: 7 DEC 2010 | DOI: 10.1002/cbic.201090091

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