ChemBioChem

Cover image for Vol. 12 Issue 17

November 25, 2011

Volume 12, Issue 17

Pages 2521–2703

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. Cover Picture: Long-Chain Lipids Are Required for the Innate Immune Recognition of Trehalose Diesters by Macrophages (ChemBioChem 17/2011) (page 2521)

      Ashna A. Khan, Stephanie H. Chee, Rene J. McLaughlin, Dr. Jacquie L. Harper, Dr. Faustin Kamena, Dr. Mattie S. M. Timmer and Dr. Bridget L. Stocker

      Article first published online: 18 NOV 2011 | DOI: 10.1002/cbic.201190080

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      The cover picture shows the differential activation of macrophages by synthetic trehalose diesters of various chain lengths. Small-chain analogues (C4–C10) show no activity and medium-length analogues (C18) show moderate activity; however, longer derivatives (C20–C26) lead to optimal activation of macrophages, as evidenced by NO production and the generation of cytokines such as IL-6 and IL-1β. For more details, see the paper by M. S. M. Timmer, B. L. Stocker et al. on p. 2572 ff.

  2. Inside Cover

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. Inside Cover: The Binding Mode of Cladocoran A to the Human Group IIA Phospholipase A2 (ChemBioChem 17/2011) (page 2522)

      Dr. Maria Chiara Monti, Maria Giovanna Chini, Dr. Luigi Margarucci, Prof. Raffaele Riccio, Prof. Giuseppe Bifulco and Prof. Agostino Casapullo

      Article first published online: 18 NOV 2011 | DOI: 10.1002/cbic.201190081

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      The inside cover picture shows the peculiar dual binding of the marine sponge metabolite Cladocoran A to the human secretory PLA2 enzyme, which is responsible for its relevant anti-inflammatory activity. For further details on the PLA2 inhibition mechanism at a molecular level, see the paper by A. Casapullo et al. on p. 2686 ff.

  3. Graphical Abstract

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. Graphical Abstract: ChemBioChem 17/2011 (pages 2523–2531)

      Article first published online: 18 NOV 2011 | DOI: 10.1002/cbic.201190082

  4. News

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

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. P450BM3 on Steroids: The Swiss Army Knife P450 Enzyme Just Gets Better (pages 2537–2539)

      Luet-Lok Wong

      Article first published online: 13 OCT 2011 | DOI: 10.1002/cbic.201100606

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      The catalytic regio- and stereoselective oxidation of aliphatic C[BOND]H bonds by using atmospheric dioxygen as the oxidant is a highly desirable reaction. Reetz and co-workers have recently reported the development of P450BM3 mutants that oxidise testosterone with greatly increased turnover activity, total stereoselectivity and >95 % regioselectivity.

    2. Mechanisms of Glycosyltransferases: The In and the Out (pages 2540–2542)

      Prof. David L. Jakeman

      Article first published online: 12 OCT 2011 | DOI: 10.1002/cbic.201100577

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      Getting into a transition state: Glycosyltransferases retain a critical role in glycobiology. The design of potent glycosyltransferase inhibitors may be facilitated by considering the mechanistic evidence presented by Davies and Davis and co-workers that strengthens the case that retaining glycosyltransferases function through a single front-side, SNi-type mechanism.

    3. Burning off DNA Methylation: New Evidence for Oxygen-Dependent DNA Demethylation (pages 2543–2545)

      Tomasz P. Jurkowski and Prof. Dr. Albert Jeltsch

      Article first published online: 13 OCT 2011 | DOI: 10.1002/cbic.201100549

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      Where do you stop? Three recent publications have described how the oxidation of 5-methylcytosine by Tet dioxygenases does not stop at the 5-hydroxymethylcytosine (5hmC) state, rather further oxidation of 5hmC is involved in DNA demethylation. The nature of the enzymes involved in this process shed light on the dynamics of epigenetic signaling and its evolutionary origin.

  6. Communications

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. SEM Observation of Wet Biological Specimens Pretreated with Room-Temperature Ionic Liquid (pages 2547–2550)

      Prof. Tetsuya Tsuda, Noriko Nemoto, Koshi Kawakami, Dr. Eiko Mochizuki, Shoko Kishida, Takako Tajiri, Prof. Toshihiro Kushibiki and Prof. Susumu Kuwabata

      Article first published online: 11 OCT 2011 | DOI: 10.1002/cbic.201100476

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      A facile pretreatment process for SEM: The use of room temperature ionic liquids (RTILs) provides an interesting method for SEM of biological specimens. We used a novel and concise method of pretreatment, excluding fixation or Au sputtering steps. Fine and smooth-textured SEM images of a wide variety of biological specimens treated in this way were observed without artefacts.

    2. Kinetic Capillary Electrophoresis with Mass-Spectrometry Detection (KCE-MS) Facilitates Label-Free Solution-Based Kinetic Analysis of Protein–Small Molecule Binding (pages 2551–2554)

      Jiayin Bao, Dr. Svetlana M. Krylova, Prof. Derek J. Wilson, Oren Reinstein, Prof. Dr. Philip E. Johnson and Prof. Dr. Sergey N. Krylov

      Article first published online: 19 OCT 2011 | DOI: 10.1002/cbic.201100617

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      Tandem tracker: Here we introduce a method for studying the kinetics of protein–small-molecule interactions based on kinetic capillary electrophoresis (KCE) separation and MS detection. Due to the variety of KCE methods and MS modes available, the KCE-MS tandem is a highly versatile platform for label-free, solution-based kinetic studies of affinity interactions.

    3. Photoswitchable Click Amino Acids: Light Control of Conformation and Bioactivity (pages 2555–2559)

      Dr. Christian Hoppmann, Dr. Peter Schmieder, Dr. Nadja Heinrich and Dr. Michael Beyermann

      Article first published online: 13 OCT 2011 | DOI: 10.1002/cbic.201100578

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      Click the switch: By using a photoswitchable click amino acid (PSCaa) a light-induced intramolecular thiol-ene click reaction with a neighboring cysteine under very mild conditions results in an azobenzene bridge (see figure). By expanding the genetic code for PSCaa the specific incorporation of photoswitch units into proteins in living cells can result in an exciting approach for studying light-controllable activity, in vivo.

    4. A Triple Spin-Labeling Strategy Coupled with DEER Analysis to Detect DNA Modifications and Enzymatic Repair (pages 2560–2563)

      Dr. Mélanie Flaender, Dr. Giuseppe Sicoli, Dr. Samia Aci-Seche, Thomas Reignier, Dr. Vincent Maurel, Christine Saint-Pierre, Dr. Yves Boulard, Dr. Serge Gambarelli and Dr. Didier Gasparutto

      Article first published online: 7 OCT 2011 | DOI: 10.1002/cbic.201100550

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      In a spin: Spin-labeled oligonucleotides produced by click chemistry can be studied by EPR, by using a DEER sequence. This was used to test a complex triple-labeling strategy with damaged DNA. Extensive and accurate analysis of DNA structure and enzymatic repair processes were performed after digestion by EndoIV (see scheme). Modified DNA structures and DNA–protein interactions can now be readily studied.

    5. DNA Nanotechnology for Nucleic Acid Analysis: DX Motif-Based Sensor (pages 2564–2567)

      Dr. Dmitry M. Kolpashchikov, Dr. Yulia V. Gerasimova and Mohammad S. Khan

      Article first published online: 18 OCT 2011 | DOI: 10.1002/cbic.201100545

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      A light on the tiles: A sensor that fluoresces in the presence of specific nucleic acids was designed and characterized. The sensor uses a molecular beacon probe and three adaptor strands to form a five-stranded assembly, a DX-tile, with a specific analyte. This sensor is a highly selective and affordable tool for the real-time analysis of DNA and RNA.

    6. Investigating Mithramycin Deoxysugar Biosynthesis: Enzymatic Total Synthesis of TDP-D-Olivose (pages 2568–2571)

      Dr. Guojun Wang, Prof. Dr. Madan K. Kharel, Dr. Pallab Pahari and Prof. Dr. Jürgen Rohr

      Article first published online: 29 SEP 2011 | DOI: 10.1002/cbic.201100540

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      Mix'n'match: Enzymatic total synthesis of TDP-D-olivose was achieved, starting from TDP-4-keto-6-deoxy-D-glucose, by combining three pathway enzymes with one cofactor-regenerating enzyme. The results also revealed that MtmC is a bifunctional enzyme that can perform a 4-ketoreduction necessary for D-olivose biosynthesis besides the previously found C-methyltransfer for D-mycarose biosynthesis.

    7. Long-Chain Lipids Are Required for the Innate Immune Recognition of Trehalose Diesters by Macrophages (pages 2572–2576)

      Ashna A. Khan, Stephanie H. Chee, Rene J. McLaughlin, Dr. Jacquie L. Harper, Dr. Faustin Kamena, Dr. Mattie S. M. Timmer and Dr. Bridget L. Stocker

      Article first published online: 11 OCT 2011 | DOI: 10.1002/cbic.201100451

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      Going to any length? Trehalose diesters of various chain lengths have been synthesised in order to determine the effect of lipid length on innate immune recognition, as determined by NO (see graph) and cytokine production by macrophages. In this work, we show that longer lipids (C20–C26) are required for macrophage activation, with C22 giving optimal activity.

  7. Full Papers

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. Identification of a Catalytic Base for Sugar Oxidation in the Pyranose 2-Oxidase Reaction (pages 2577–2586)

      Thanyaporn Wongnate, Jeerus Sucharitakul and Pimchai Chaiyen

      Article first published online: 19 OCT 2011 | DOI: 10.1002/cbic.201100564

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      Abstract concept: Pyranose 2-oxidase catalyzes the oxidation of aldopyranoses to form 2-keto sugars and H2O2. By using site-directed mutagenesis, transient kinetics, and pH-dependence studies, the unprotonated form of a conserved residue (H548) was identified as a catalytic base to abstract the 2-hydroxyl proton of D-glucose, and thus to initiate hydride transfer from the substrate to the flavin.

    2. Conformational Analysis of Bivalent Estrogen Receptor Ligands: From Intramolecular to Intermolecular Binding (pages 2587–2598)

      Min Shan, Alexander Bujotzek, Frank Abendroth, Anja Wellner, Prof. Dr. Ronald Gust, Prof. Dr. Oliver Seitz, Dr. Marcus Weber and Prof. Dr. Rainer Haag

      Article first published online: 25 OCT 2011 | DOI: 10.1002/cbic.201100529

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      Shape up: Evaluation of estrogen receptor binding with 13 bivalent raloxifene ligands tethered by flexible spacers of different lengths in vitro and in silico indicated that ligand conformation significantly influenced the binding affinities in the aqueous environment. Moreover, two bivalent binding modes—intra- and intermolecular—were hypothesized to explain their different binding behaviors.

    3. NMR Spectroscopic Investigations of the Activated p38α Mitogen-Activated Protein Kinase (pages 2599–2607)

      Gerd Nielsen and Prof. Dr. Harald Schwalbe

      Article first published online: 19 OCT 2011 | DOI: 10.1002/cbic.201100527

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      Flexible communicator: We have assigned the activated p38α by liquid-state NMR spectroscopy and compared it to the assignment of inactivated p38α as well as X-ray structures. We observed large structural and dynamic changes in the activation loop and two further loop segments, as well as changes in H/D exchange properties, and we assessed the dynamic changes in a ternary complex mimicking binding of ATP/Mg2+ and a substrate peptide to activated p38α.

    4. Mechanistic Basis for RNA Aptamer-Based Induction of TetR (pages 2608–2614)

      Dr. Markus Steber, Dr. Amit Arora, Dr. Jan Hofmann, Prof. Dr. Bernhard Brutschy and Prof. Dr. Beatrix Suess

      Article first published online: 21 OCT 2011 | DOI: 10.1002/cbic.201100503

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      Head-lining: The TetR aptamer induces TetR controlled gene expression. The binding epitope of the aptamer was identified (blue) and overlaps with the helix-turn-helix motif (yellow). Tetracycline-induced conformational changes of TetR impair aptamer binding.

    5. Mechanistic Insight into the Catalytic Activity of ββα-Metallonucleases from Computer Simulations: Vibrio vulnificus Periplasmic Nuclease as a Test Case (pages 2615–2622)

      Juan A. Bueren-Calabuig, Claire Coderch, Dr. Eva Rico, Prof. Antonio Jiménez-Ruiz and Prof. Federico Gago

      Article first published online: 6 OCT 2011 | DOI: 10.1002/cbic.201100485

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      Parsimony in water splitting: Although two water molecules are usually depicted in the catalytic mechanism of ββα-metallonucleases, one to cleave the phosphodiester bond and another to protonate the leaving hydroxylate, our computational results strongly suggest that it is the same water molecule from bulk solvent that provides both the nucleophilic hydroxide and the proton necessary to complete the reaction (see scheme).

    6. Photoactivatable Caged Cyclic RGD Peptide for Triggering Integrin Binding and Cell Adhesion to Surfaces (pages 2623–2629)

      Melanie Wirkner, Simone Weis, Dr. Verónica San Miguel, Dr. Marta Álvarez, Dr. Radu A. Gropeanu, Dr. Marcelo Salierno, Anne Sartoris, Dr. Ronald E. Unger, Prof. C. James Kirkpatrick and Dr. Aránzazu del Campo

      Article first published online: 4 NOV 2011 | DOI: 10.1002/cbic.201100437

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      A photosensitive caged RGD peptide is used for efficient phototriggering of cell attachment. Spatiotemporal control over cell attachment and dose-dependent exposure allowed in situ generation of cell patterns and gradients onto well-defined RGD surface concentrations.

    7. Creation of Aggregation-Defective α-Synuclein Variants by Engineering the Sequence Connecting β-Strand-Forming Domains (pages 2630–2639)

      Michael Hernandez, Sofia Golbert, Li Guo Zhang and Prof. Jin Ryoun Kim

      Article first published online: 13 OCT 2011 | DOI: 10.1002/cbic.201100430

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      Don't stick together: Varying the linker sequence connecting its β-strand-forming domains affects or even inhibits the aggregation of α-synuclein. Although the physicochemical properties of the linker region (evaluated based on an intrinsic property of a single amino acid) play a significant role in aggregation, an additional factor can also determine the aggregation behavior of αS linker variants.

    8. Dynamic Substrate Enhancement for the Identification of Specific, Second-Site-Binding Fragments Targeting a Set of Protein Tyrosine Phosphatases (pages 2640–2646)

      Dr. Marco F. Schmidt, Dr. Matthew R. Groves and Prof. Dr. Jörg Rademann

      Article first published online: 3 NOV 2011 | DOI: 10.1002/cbic.201100414

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      Looking into second site:p-Formyl-phenyl phosphate was identified as a generic substrate for protein tyrosine phosphatases (PTPs) and was used to scrutinize the proteins' secondary binding site for specifically binding fragments. Binding fragments were detected by an amplified turnover of the substrate in a dynamic ligation reaction and were developed to highly specific PTP inhibitors.

    9. Heteromeric Assembled Polypeptidic Artificial Hydrolases with a Six-Helical Bundle Scaffold (pages 2647–2658)

      Yu Bai, Yanbo Ling, Dr. Weiguo Shi, Dr. Lifeng Cai, Qiyan Jia, Prof. Shibo Jiang and Prof. Keliang Liu

      Article first published online: 29 SEP 2011 | DOI: 10.1002/cbic.201100311

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      Bundling up: Interactive C- and N-peptides (see scheme) bearing engineered functional groups were found to form structured six-helical bundles (6HB) when mixed. The 6HB formation brings the functional groups to cooperative positions and forms an enzyme-like active site. The designed 6HB catalyst showed enzyme-like rate enhancement and substrate affinity for hydrolytic reaction of p-nitrophenyl acetate.

    10. Aptamers can Discriminate Alkaline Proteins with High Specificity (pages 2659–2666)

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

      Article first published online: 21 OCT 2011 | DOI: 10.1002/cbic.201100252

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      Basic selection: Previous selections have yielded DNA aptamers with high affinity but low specificity to individual basic histone proteins. Here we report the in vitro selection of a DNA aptamer that binds to histone H4 with a Kd of 13 nM and distinguishes other core histone proteins with 100–480-fold selectivity.

    11. Biosynthesis of Sesqui- and Diterpenes by the Gibberellin Producer Fusarium fujikuroi (pages 2667–2676)

      Nelson L. Brock, Prof. Dr. Bettina Tudzynski and Dr. Jeroen S. Dickschat

      Article first published online: 11 OCT 2011 | DOI: 10.1002/cbic.201100516

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      Volatile diterpenes: In addition to sesquiterpenes, several biosynthetically related diterpenes were identified in headspace extracts from Fusarium fujikuroi. Gene knockouts revealed the common production of all diterpenes by the bifunctional ent-copalyl diphosphate synthase/ent-kaurene synthase involved in gibberellin biosynthesis. Feeding experiments with deuterated mevalonolactones gave insights in the stereochemical course of the diterpene biosynthesis.

    12. Two Pathways for Pyrrole Formation in Coumermycin A1 Biosynthesis: The Central Pyrrole Moiety Is Formed From L-Threonine (pages 2677–2685)

      Stefanie Siebenberg, Nadja Burkard, Anna Knuplesch, Dr. Bertolt Gust, Prof. Dr. Stephanie Grond and Prof. Dr. Lutz Heide

      Article first published online: 27 SEP 2011 | DOI: 10.1002/cbic.201100494

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      Two pathways to pyrroles: The antibiotic coumermycin A1 contains pyrrole moieties derived from L-proline. Here, we show that the other unique pyrrole moiety of coumermycin A1 is formed from L-threonine with the involvement of the genes couR1couR4 (see scheme).

    13. The Binding Mode of Cladocoran A to the Human Group IIA Phospholipase A2 (pages 2686–2691)

      Dr. Maria Chiara Monti, Maria Giovanna Chini, Dr. Luigi Margarucci, Prof. Raffaele Riccio, Prof. Giuseppe Bifulco and Prof. Agostino Casapullo

      Article first published online: 27 SEP 2011 | DOI: 10.1002/cbic.201100478

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      The marine corps: Here we show that the inactivation mechanism of human synovial phospholipases A2 by cladocoran A is based on noncovalent occupation of the active site by the inhibitor (see figure), which chelates the essential calcium ion.

    14. Evaluation of a Fluorescent Derivative of AMD3100 and its Interaction with the CXCR4 Chemokine Receptor (pages 2692–2698)

      Dr. James C. Knight, Dr. Andrew J. Hallett, Dr. Andrea Brancale, Dr. Stephen J. Paisey, Dr. Richard W. E. Clarkson and Prof. Peter G. Edwards

      Article first published online: 13 OCT 2011 | DOI: 10.1002/cbic.201100441

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      A fluorescent derivative of the CXCR4 antagonist, AMD3100, and a series of binuclear transition metal complexes have been evaluated. The fluorescence of the free ligand has been shown to be enhanced and dramatically quenched in the presence of zinc and copper, respectively. Here we examine the ability of the free ligand and corresponding zinc complex to assess cellular CXCR4 expression.

  8. Book Reviews

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. Lipids and Cellular Membranes in Amyloid Diseases. Edited by Raz Jelinek. (pages 2699–2700)

      Gerhard Gröbner

      Article first published online: 26 OCT 2011 | DOI: 10.1002/cbic.201100650

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      Wiley-VCH, Weinheim 2011, 296 pp., hardcover € 129.00.—ISBN 978-3-527-32860-4

    2. RNA Biology: An Introduction. By Gunter Meister. (page 2700)

      Franz Narberhaus

      Article first published online: 28 OCT 2011 | DOI: 10.1002/cbic.201100657

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      Wiley-VCH, Weinheim 2011, XVI+363 pp., softcover € 59.00.—ISBN 978-3-527-32278-7

  9. Preview

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Highlights
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
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      Preview: ChemBioChem 18/2011 (page 2703)

      Article first published online: 18 NOV 2011 | DOI: 10.1002/cbic.201190084

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