ChemBioChem

Cover image for Vol. 12 Issue 4

March 7, 2011

Volume 12, Issue 4

Pages 493–651

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Reviews
    11. Preview
    1. Cover Picture: Oxorhenium-Mediated Assembly of Noncyclic Selective Integrin Antagonists: A Combinatorial Approach (ChemBioChem 4/2011) (page 493)

      Dr. Marie Aufort, Dr. Marta Gonera, Dr. Julien Le Gal, Bertrand Czarny, Dr. Loïc Le Clainche, Dr. Robert Thai and Dr. Christophe Dugave

      Version of Record online: 25 FEB 2011 | DOI: 10.1002/cbic.201190010

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      The cover picture shows the TcO3+- or ReO3+-mediated assembly of independent chemical modules to form a library of antagonists of integrins, αβ-heterodimeric integral proteins implicated in cancer development (bottom). Parallel combination of 36 “NS2 modules” bearing a carboxylate (module 15d) and eight “S modules” grafted with a guanidinium group (module D) together with ReO3+ enabled the synthesis of 288 oxorhenium RGD mimetics. Library screening led to the selection of six complexes that exhibit micromolar and sub-micromolar affinities for integrins αVβ3, αIIbβ3 and αVβ5 and interesting selectivities. Complex Re–D15d, shown here, was identified as the antagonist with the greatest affinity and selectivity (IC50=240 nm for αVβ3). The corresponding Tc–D15d complex exhibited a satisfactory stability in mice plasma. Oxotechnetium-assembled RGD mimetics should be assayed for the molecular imaging of integrin-dependent cancer progression in nude mice bearing a human tumor xenograft. For more information see the paper by C. Dugave et al. on p. 583 ff.

  2. Inside Cover

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Reviews
    11. Preview
    1. Inside Cover: IspG-Catalyzed Positional Isotopic Exchange in Methylerythritol Cyclodiphosphate of the Deoxyxylulose Phosphate Pathway: Mechanistic Implications (ChemBioChem 4/2011) (page 494)

      Dr. Youli Xiao, Debra Rooker, Quincy You, Prof. Dr. Caren L. Freel Meyers and Prof. Dr. Pinghua Liu

      Version of Record online: 25 FEB 2011 | DOI: 10.1002/cbic.201190011

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      The inside cover picture shows that the enzyme IspG in the deoxyxylulose phosphate pathway can mediate a reversible C[BOND]O bond cleavage at an inert position. This hypothesis was supported by the detection of diphosphate ester bridging and terminal oxygen atom exchange. For more information, see the communication by P.-h. Liu et al. on p. 527 ff.

  3. Graphical Abstract

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

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

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Reviews
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    1. Interaction of Vesicles: Adhesion, Fusion and Multicompartment Systems Formation (pages 510–521)

      Dr. Constantinos M. Paleos, Dr. Dimitris Tsiourvas and Dr. Zili Sideratou

      Version of Record online: 17 FEB 2011 | DOI: 10.1002/cbic.201000614

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      Bilayers in contact: Interaction of complementary or oppositely charged vesicles leads to adhesion, followed in certain cases by fusion, and occasionally by multicompartment systems formation. These processes are critically dependent on the functionalization of vesicle surfaces.

  6. Highlight

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Reviews
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    1. Shedding Light on the Ghrelin/GOAT Metabolism Saga (pages 523–525)

      Dr. Amanda L. Garner and Prof. Kim D. Janda

      Version of Record online: 20 JAN 2011 | DOI: 10.1002/cbic.201000777

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      Getting the GOAT: The identification of a ghrelin O-acyltransferase (GOAT) inhibitor displaying metabolic modulatory activities has recently been reported. This research might provide a link for answering key questions relating to ghrelin's role(s) in obesity and diabetes.

  7. Communications

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Reviews
    11. Preview
    1. IspG-Catalyzed Positional Isotopic Exchange in Methylerythritol Cyclodiphosphate of the Deoxyxylulose Phosphate Pathway: Mechanistic Implications (pages 527–530)

      Dr. Youli Xiao, Debra Rooker, Quincy You, Prof. Dr. Caren L. Freel Meyers and Prof. Dr. Pinghua Liu

      Version of Record online: 26 JAN 2011 | DOI: 10.1002/cbic.201000716

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      H218O under the bridge: Recently, the deoxyxylulose phosphate (DXP) pathway was discovered to be a second pathway supplying isoprenoid biosynthetic precursors. One of steps is an IspG-catalyzed reductive deoxygenation of methylerythritol cyclodiphosphate (MEcPP) to 4-hydroxyl-3-methyl-2-(E)-1-diphosphate (HMBPP). Using [2-13C,18O]-MEcPP, we detected the positional isotopic exchange for the bridging oxygen in MEcPP.

    2. The 2-Oxoglutarate-Dependent Oxygenase JMJD6 Catalyses Oxidation of Lysine Residues to give 5S-Hydroxylysine Residues (pages 531–534)

      Monica Mantri, Nikita D. Loik, Dr. Refaat B. Hamed, Dr. Timothy D. W. Claridge, Dr. James S. O. McCullagh and Prof. Dr. Christopher J. Schofield

      Version of Record online: 18 JAN 2011 | DOI: 10.1002/cbic.201000641

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      Amino acid analyses reveal that JMJD6-catalysed hydroxylation of RNA-splicing regulatory protein fragments occurs to give hydroxylysine products with 5S stereochemistry. This contrasts with collagen lysyl hydroxylases, which give 5R-hydroxylated products. The work suggests that more than one subfamily of lysyl hydroxylases has evolved and illustrates the importance of stereochemical assignments in proteomic analyses.

    3. Synthetic Caged DAG-lactones for Photochemically Controlled Activation of Protein Kinase C (pages 535–539)

      Dr. Wataru Nomura, Dr. Tetsuo Narumi, Nami Ohashi, Yuki Serizawa, Nancy E. Lewin, Dr. Peter M. Blumberg, Prof. Toshiaki Furuta  and Prof. Hirokazu Tamamura

      Version of Record online: 18 JAN 2011 | DOI: 10.1002/cbic.201000670

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      Switching on kinases: Synthetic caged DAG-lactones have been developed and showed decreases of two orders of magnitude, relative to the corresponding parent compounds, in their binding affinities towards PKC. The caged compounds had no effect on the translocation of PKC until after photoactivation. This approach is a potentially powerful tool for probing the PKC signaling cascade.

    4. Mutational Biosynthesis of Ansamitocin Antibiotics: A Diversity-Oriented Approach to Exploit Biosynthetic Flexibility (pages 540–547)

      Dr. Tobias Knobloch, Dr. Kirsten Harmrolfs, Dr. Florian Taft, Binia Thomaszewski, Dr. Florenz Sasse and Prof. Dr. Andreas Kirschning

      Version of Record online: 27 JAN 2011 | DOI: 10.1002/cbic.201000608

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      Mutasynthesis: Feeding aminobenzoic acid derivatives to a Actinosynnema pretiosum mutant that could not biosynthesize the essential starter unit 3-amino-5-hydroxybenzoic acid led to novel ansamitocin derivatives, which were isolated, characterized and subjected to in vitro biological testing. Our studies provided insights into the flexibility of ansamitocin biosynthesis in A. pretiosum and gave a deeper understanding of structure–activity relationships.

    5. Live Cell Luminescence Imaging As a Function of Delivery Mechanism (pages 548–551)

      Xiaohe Tian, Dr. Martin R. Gill , Dr. Irene Cantón, Dr. Jim A. Thomas and Dr. Giuseppe Battaglia

      Version of Record online: 4 FEB 2011 | DOI: 10.1002/cbic.201000743

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      Mitochondria in live cells can be imaged with a ruthenium(II) complex that usually binds and images nuclear DNA. The cellular uptake mechanism of this probe was changed by using a biocompatible pH-sensitive polymersome vector. This change in delivery route, determines the final cellular location of the probe and thus modulates its imaging properties.

    6. Expanding and Engineering the Genetic Code in a Single Expression Experiment (pages 552–555)

      Michael G. Hoesl  and Prof. Dr. Nediljko Budisa 

      Version of Record online: 18 JAN 2011 | DOI: 10.1002/cbic.201000586

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      Expanding and engineering the code simultaneously: This concept was experimentally realized in a single in vivo expression experiment whereby residue-specific, sense codon reassignments Met[RIGHTWARDS ARROW]Nle/Pro[RIGHTWARDS ARROW](4S-F)Pro (code engineering) were combined with position-specific STOP[RIGHTWARDS ARROW]Bpa read-through by an amber suppressor tRNA (code expansion).

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      Morphological Differences between β2-Microglobulin in Fibrils and Inclusion Bodies (pages 556–558)

      Garrick F. Taylor, Prof. Stephen P. Wood, Karsten Mörs, Prof. Clemens Glaubitz, Dr. Jörn M. Werner and Dr. Philip T. F. Williamson

      Version of Record online: 26 JAN 2011 | DOI: 10.1002/cbic.201000582

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      Over expression of proteins in E. coli frequently results in the production of inclusion bodies. Although β2-microglobulin frequently forms fibrillar structures, our studies reveal significant differences between the protein in fibrils and inclusion bodies. This suggests that the formation of fibrils in inclusion bodies is dependent on the propensity of the protein to form fibrillar structures.

  8. Full Papers

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Reviews
    11. Preview
    1. Polypeptide Conjugate Binders that Discriminate between Two Isoforms of Human Carbonic Anhydrase in Human Blood (pages 559–566)

      Dr. Lotta T. Tegler, Dr. Karin Fromell, Prof. Bengt-Harald Jonsson, Dr. Johan Viljanen, Dr. Cecilia Winander, Dr. Jonas Carlsson and Prof. Lars Baltzer

      Version of Record online: 24 JAN 2011 | DOI: 10.1002/cbic.201000556

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      Alternatives to antibodies: Polypeptide conjugates from benzenesulfonamide and a set of 42-residue designed polypeptides with no prior relationship to HCAII were screened for affinity towards HCAII. The identified tight binder 4-C37L34-B showed an affinity of 17 nM and discriminated against the enzyme isoform HCAI by a factor of 30 although HCAII and HCAI show 60 % homology.

    2. Structure–Function Relationships of Phenoxazine Nucleosides for Identification of Mismatches in Duplex DNA by Fluorescence Spectroscopy (pages 567–575)

      Haraldur Gardarsson, Dr. Ajaykumar S. Kale and Prof. Snorri Th. Sigurdsson

      Version of Record online: 14 FEB 2011 | DOI: 10.1002/cbic.201000478

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      A small change goes a long way: Structurally related fluorescent phenoxazine-based nucleosides tCO and Çf exhibit vastly different mismatch-detection capabilities and a large flanking sequence dependence in duplex DNA; tCO shows poorer discrimination of mismatches than previously reported for Çf.

    3. Identification of CYP106A2 as a Regioselective Allylic Bacterial Diterpene Hydroxylase (pages 576–582)

      Sabrina Bleif, Dr. Frank Hannemann, Dr. Michael Lisurek, Dr. Jens Peter von Kries, Dr. Josef Zapp, Matthias Dietzen, Prof. Dr. Iris Antes and Prof. Dr. Rita Bernhardt

      Version of Record online: 26 JAN 2011 | DOI: 10.1002/cbic.201000404

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      Bacterial allylic hydroxylation: CYP106A2 has been identified as the first reported bacterial cytochrome P450 diterpene hydroxylase. It is able to carry out a one-step regioselective allylic hydroxylation of the diterpene abietic acid. An effective whole-cell catalyst for the selective allylic 12α- and 12β-hydroxylation was developed.

    4. Oxorhenium-Mediated Assembly of Noncyclic Selective Integrin Antagonists: A Combinatorial Approach (pages 583–592)

      Dr. Marie Aufort, Dr. Marta Gonera, Dr. Julien Le Gal, Bertrand Czarny, Dr. Loïc Le Clainche, Dr. Robert Thai and Dr. Christophe Dugave

      Version of Record online: 8 FEB 2011 | DOI: 10.1002/cbic.201000700

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      Integrin antagonism: The synthesis and screening of a library of 288 RGD oxorhenium complexes led to the identification of selective submicromolar antagonists of integrins αVβ3, αIIbβ3 and αVβ5. Their [99mTc]-labeled equivalents were shown to be stable in murine plasma.

    5. Enhanced Expression and Purification of Fungal Galactose Oxidase in Escherichia coli and Use for Analysis of a Saturation Mutagenesis Library (pages 593–601)

      Dr. Sarah E. Deacon  and Prof. Michael J. McPherson 

      Version of Record online: 24 JAN 2011 | DOI: 10.1002/cbic.201000634

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      Optimised expression: Galactose oxidase is a fungal enzyme that is poorly expressed in Escherichia coli. Mutations and optimisation of growth and purification conditions resulted in a dramatic increase in production of functional enzyme. A saturation-mutagenesis study of residue Cys383 demonstrates the potential for using this improved expression system for directed evolution and associated structural studies.

    6. Systematic Screening for Catalytic Promiscuity in 4-Oxalocrotonate Tautomerase: Enamine Formation and Aldolase Activity (pages 602–609)

      Ellen Zandvoort, Bert-Jan Baas, Prof. Dr. Wim J. Quax and Dr. Gerrit J. Poelarends

      Version of Record online: 3 FEB 2011 | DOI: 10.1002/cbic.201000633

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      Prozymes: A systematic screening strategy to discover new promiscuous carbonyl-transformation activities in 4oxalocrotonate tautomerase (4-OT) is reported. The N-terminal proline of this enzyme provides a chemical functionality in the active site that might be suitable for enamine catalysis. It is shown that the aldol condensation of acetaldehyde with benzaldehyde is catalyzed by 4-OT.

    7. Minimal Substrate Features for Erm Methyltransferases Defined by Using a Combinatorial Oligonucleotide Library (pages 610–614)

      Lykke H. Hansen, Dr. Sune Lobedanz , Prof. Stephen Douthwaite, Dr. Khalil Arar, Prof. Jesper Wengel, Prof. Finn Kirpekar and Prof. Birte Vester

      Version of Record online: 24 JAN 2011 | DOI: 10.1002/cbic.201000606

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      Discovering the motif: Erm methyltransferases are prevalent in pathogenic bacteria and confer resistance to macrolide, lincosamide, and streptogramin B antibiotics by modifying the rRNA. With a view to developing specific inhibitors of this resistance mechanism, we have used a combinatorial approach to identify motifs within substrates (two-stranded substrate-analogue shown) that enhance or impede Erm methylation.

    8. Baicalein Inhibits Formation of α-Synuclein Oligomers within Living Cells and Prevents Aβ Peptide Fibrillation and Oligomerisation (pages 615–624)

      Jia-Hong Lu, Mustafa Taleb Ardah, Siva Sundara Kumar Durairajan, Liang-Feng Liu, Dr. Li-Xia Xie, Prof. Dr. Wang-Fun David Fong, Prof. Dr. Mohamed Y. Hasan, Dr. Jian-Dong Huang, Prof. Dr. Omar M. A. El-Agnaf and Prof. Dr. Min Li

      Version of Record online: 26 JAN 2011 | DOI: 10.1002/cbic.201000604

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      Arrested aggregation: Baicalein, a flavonoid from the Chinese herbal medicine Scutellaria baicalensis Georgi, is a potent inhibitor of α-syn oligomerisation both in cell-free and cellular systems, and is also a effective inhibitor of α-syn fibrillation in cell-free systems. It inhibits the formation of α-syn oligomers in SH-SY5Y and Hela cells, and protects SH-SY5Y cells from α-syn-oligomer-induced toxicity.

    9. SSTR1- and SSTR3-Selective Somatostatin Analogues (pages 625–632)

      Dr. Rosario Ramón , Pablo Martín-Gago, Prof. Xavier Verdaguer , Prof. Maria J. Macias , Pau Martin-Malpartida, Dr. Jimena Fernández-Carneado, Marc Gomez-Caminals, Dr. Berta Ponsati, Prof. Pilar López-Ruiz, Maria Alicia Cortés, Begoña Colás and Prof. Antoni Riera 

      Version of Record online: 21 JAN 2011 | DOI: 10.1002/cbic.201000597

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      Flexible strength: The two enantiomers of amino acid 3-(3′-quinolyl)alanine (Qla) have been synthesized. They were then used in the synthesis of two Somatostatin analogues that exhibit strong affinity to receptors SSTR1 and SSTR3. The conformational flexibility of these peptides, greater than that of Somatostatin, might be beneficial to the interaction with the receptors.

    10. The Chemoselective One-Step Alkylation and Isolation of Thiophosphorylated Cdk2 Substrates in the Presence of Native Cysteine (pages 633–640)

      Dr. Sarah E. Lee, Dr. Lucy M. Elphick, Dr. Holger B. Kramer, Dr. Alexandra M. E. Jones, Dr. Emma S. Child, Dr. Alexandra A. Anderson, Dr. Laurent Bonnac, Dr. Natsuko Suwaki, Dr. Benedikt M. Kessler, Prof. Dr. Véronique Gouverneur and Dr. David J. Mann

      Version of Record online: 8 FEB 2011 | DOI: 10.1002/cbic.201000528

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      It's a kinase magic: The identification of protein substrates is hampered by the large number of kinases active in cells at a given time. Here we use a chemical genetic approach to specifically label the substrates of an analogue-sensitive kinase with thiophosphate and use pH-dependent S-alkylation to selectively recover thiophosphorylated peptides.

    11. Chromophore Exchange in the Blue Light-Sensitive Photoreceptor YtvA from Bacillus subtilis (pages 641–646)

      Dr. Madina Mansurova, Pierre Scheercousse, Julian Simon, Marianne Kluth and Prof. Dr. Wolfgang Gärtner

      Version of Record online: 21 JAN 2011 | DOI: 10.1002/cbic.201000515

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      Shuffling chromophores: A successful, routine chromophore-exchange protocol allows chemically synthesized, structurally modified chromophores (used chromophores see on the formula) instead of the naturally present flavin mononucleotide (FMN) chromophore to be introduced under mild, protein-friendly conditions. The photochemical properties of newly incorporated flavin derivatives in YtvA's LOV domain were investigated and described.

  9. Book Reviews

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Reviews
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    1. Protein Folding and Metal Ions: Mechanisms, Biology and Disease. Edited by Cláudio M. Gomes and Pernilla Wittung-Stafshede. (page 647)

      Jia-Cherng Horng

      Version of Record online: 24 JAN 2011 | DOI: 10.1002/cbic.201100017

      CRC Press, Boca Raton 2010, XIV+294 pp., hardcover $ 149.95.—ISBN 978-1-4398-0964-8

    2. Computational Protein–Protein Interactions. Edited by Ruth Nussinov and Gideon Schreiber. (page 648)

      Roland Stauber and Carolin Bier

      Version of Record online: 15 FEB 2011 | DOI: 10.1002/cbic.201100081

      CRC Press, Boca Raton 2010, XVII+317 pp., hardcover $ 119.95.—ISBN 978-1-4200-7005-7

    3. Assay Development: Fundamentals and Practices. By Ge Wu. (pages 648–649)

      Snehasikta Swarnakar and Tarun K. Dhar

      Version of Record online: 15 FEB 2011 | DOI: 10.1002/cbic.201100040

      Wiley, Hoboken 2010, XX+425 pp., hardcover $ 139.95.—ISBN 978-0-470-19115-6

  10. Preview

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. News
    6. Review
    7. Highlight
    8. Communications
    9. Full Papers
    10. Book Reviews
    11. Preview
    1. You have free access to this content
      Preview: ChemBioChem 5/2011 (page 651)

      Version of Record online: 25 FEB 2011 | DOI: 10.1002/cbic.201190014

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