ChemBioChem

Cover image for Vol. 10 Issue 17

November 23, 2009

Volume 10, Issue 17

Pages 2677–2807

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. Corrigendum
    6. News
    7. Minireviews
    8. Highlight
    9. Communications
    10. Full Papers
    11. Book Reviews
    12. Preview
    1. Cover Picture: Control of Lipase Enantioselectivity by Engineering the Substrate Binding Site and Access Channel (ChemBioChem 17/2009) (page 2677)

      Vincent Lafaquière, Sophie Barbe, Sophie Puech-Guenot, David Guieysse, Juan Cortés, Pierre Monsan, Thierry Siméon, Isabelle André and Magali Remaud-Siméon

      Version of Record online: 17 NOV 2009 | DOI: 10.1002/cbic.200990076

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      The cover picture highlights the concept of adapting path-planning algorithms, originating from robotics, to investigating various molecular-motion problems, such as the access of R and S enantiomers to the active site of an enzyme. With this technique, both the enzyme and the substrates are modelled as polyarticulated mechanisms. On p. 2760 ff. of this issue, M. Remaud-Siméon et al. show how the combined use of computational approaches and molecular-engineering techniques allowed the fast isolation of several mutants of the lipase from Burkholderia cepacia with remarkably enhanced (up to tenfold) or reversed enantioselectivity compared to the wild-type enzyme. By re-engineering the deeply buried substrate binding site and access channel of the B. cepacia lipase, highly enantioselective biocatalysts with a 15-fold enhanced specific activity compared to the parental enzyme were developed for the kinetic resolution of 2-substituted racemic acids. Model of the Justin Robot from the German Aerospace Center (DLR), Institute of Robotics and Mechatronics.

  2. Inside Cover

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. Corrigendum
    6. News
    7. Minireviews
    8. Highlight
    9. Communications
    10. Full Papers
    11. Book Reviews
    12. Preview
    1. Inside Cover: A Fragment-Based Approach to Probing Adenosine Recognition Sites by Using Dynamic Combinatorial Chemistry (ChemBioChem 17/2009) (page 2678)

      Duncan E. Scott, Gwen J. Dawes, Michiyo Ando, Chris Abell and Alessio Ciulli

      Version of Record online: 17 NOV 2009 | DOI: 10.1002/cbic.200990077

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      The inside cover picture shows the active site of pantothenate synthetase templating a dynamic combinatorial library of disulfides. Library members were formed dynamically between anchor ligand 5′-deoxy-5′-thioadenosine and thiol fragments to probe interactions in adjacent pockets. The best binder was identified by HPLC analysis and confirmed by X-ray crystallography. For more information, see the paper by A. Ciulli, C. Abell et al. on p. 2772 ff.

  3. Graphical Abstract

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

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. Corrigendum
    6. News
    7. Minireviews
    8. Highlight
    9. Communications
    10. Full Papers
    11. Book Reviews
    12. Preview
    1. You have free access to this content
      Delivery of Therapeutic RNAi by Nanovehicles (page 2685)

      Huricha Baigude and Tariq M. Rana

      Version of Record online: 17 NOV 2009 | DOI: 10.1002/cbic.200990079

      This article corrects:

      Delivery of Therapeutic RNAi by Nanovehicles

      Vol. 10, Issue 15, 2449–2454, Version of Record online: 17 AUG 2009

  5. News

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

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. Corrigendum
    6. News
    7. Minireviews
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    9. Communications
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    1. Chemical Modification of Oligonucleotides for Therapeutic, Bioanalytical and other Applications (pages 2691–2703)

      Neil M. Bell and Jason Micklefield

      Version of Record online: 8 SEP 2009 | DOI: 10.1002/cbic.200900341

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      Made-to-order: We discuss modified oligonucleotides and mimics that have been developed with improved physicochemical and biological properties, and utilised in a wide range of applications. New conjugation strategies have been developed to aid delivery and cellular localisation. Modified oligonucleotides are also widely used as probes for bioanalytical applications and as building blocks for assembly of higher-order nanostructures.

    2. Ultrahigh-Throughput FACS-Based Screening for Directed Enzyme Evolution (pages 2704–2715)

      Guangyu Yang and Stephen G. Withers

      Version of Record online: 24 SEP 2009 | DOI: 10.1002/cbic.200900384

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      The FACS of life: Fluorescence-activated cell sorting (FACS) has recently emerged as a powerful tool for screening enzyme libraries. The key step in developing a FACS screening method is to establish a linkage between genotype and phenotype. In this minireview, we discuss recent advances in FACS-based screening for enzymatic activity and especially focus on the novel approaches that couple the target enzymatic activity with a detectable fluorescent signal.

  7. Highlight

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. Corrigendum
    6. News
    7. Minireviews
    8. Highlight
    9. Communications
    10. Full Papers
    11. Book Reviews
    12. Preview
    1. Dynamic Sequence Modification: A Design Principle for Synthetic Informational Oligomers (pages 2717–2719)

      Ulf Diederichsen

      Version of Record online: 14 OCT 2009 | DOI: 10.1002/cbic.200900543

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      With thioester peptide nucleic acids a new kind of oligonucleotide analogues is pictured. The attachment of nucleobases (red) is reversible as indicated by sequence adaptability to DNA template strands (black). Amino acid side chains (green) and a regular peptide backbone (blue) in principle still allow protein-like function. Evidence for engineering functional and informational oligomers as well as for prebiotic chemistry is discussed.

  8. Communications

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. Corrigendum
    6. News
    7. Minireviews
    8. Highlight
    9. Communications
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    11. Book Reviews
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    1. Discovery of a Small-Molecule Inhibitor of the KIX–KID Interaction (pages 2721–2724)

      Bingbing X. Li and Xiangshu Xiao

      Version of Record online: 6 OCT 2009 | DOI: 10.1002/cbic.200900552

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      Are you too small? The small molecule (MW=297) shown here was discovered to be an inhibitor of the KIX–KID interaction by using a novel Renilla luciferase complementation assay. This compound also inhibits CREB-mediated gene transcription in living cells.

    2. Dehydrocoelenterazine is the Organic Substance Constituting the Prosthetic Group of Pholasin (pages 2725–2729)

      Eiko Tanaka, Masaki Kuse and Toshio Nishikawa

      Version of Record online: 7 OCT 2009 | DOI: 10.1002/cbic.200900503

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      A little light analysis: Pholasin is composed of dehydrocoelenterazine (DCL), an organic substance from the photoprotein of luminous squid. Treatment of Pholasin with excess dithiothreitol (DTT) produced a solution containing a DCL–DTT adduct, whose structure was determined by LC-MS analysis and compared with the authentic compound. This demonstrated that DCL constituted the prosthetic group of Pholasin.

    3. The Global Virulence Regulators VsrAD and PhcA Control Secondary Metabolism in the Plant Pathogen Ralstonia solanacearum (pages 2730–2732)

      Patrick Schneider, Jonathan M. Jacobs, João Neres, Courtney C. Aldrich, Caitilyn Allen, Markus Nett and Dirk Hoffmeister

      Version of Record online: 14 OCT 2009 | DOI: 10.1002/cbic.200900510

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      Two transcriptional regulators in the bacterium Ralstonia solanacearum (VsrAD and PhcA) that play a central role for virulence were shown to affect secondary metabolism as well; this led to the identification of a new natural product, ralfuranone. The results shed light on the regulation and biosynthetic capacities for secondary metabolism of this plant pathogen.

    4. Artificial Protein Block Copolymers Blocks Comprising Two Distinct Self-Assembling Domains (pages 2733–2735)

      Jennifer S. Haghpanah, Carlo Yuvienco, Deniz E. Civay, Hanna Barra, Peter J. Baker, Sachin Khapli, Natalya Voloshchuk, Susheel K. Gunasekar, Murugappan Muthukumar and Jin K. Montclare

      Version of Record online: 5 OCT 2009 | DOI: 10.1002/cbic.200900539

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      It's the way that you do it: Block polymers composed of elastin (E) and COMPcc (C) domains (see figure) have been synthesised and characterised. The protein motifs were chosen for their structures and distinct self-assembly modes. We demonstrate that the micro- and macrostructures of the polymers are dictated by the orientation of the fusions and the number of repeated blocks.

    5. A Cost-Effective Labeling Strategy for the NMR Study of Large Proteins: Selective 15N-Labeling of the Tryptophan Side Chains of Prolyl Oligopeptidase (pages 2736–2739)

      Teresa Tarragó, Birgit Claasen, Nessim Kichik, Ricard A. Rodriguez-Mias, Margarida Gairí and Ernest Giralt

      Version of Record online: 1 OCT 2009 | DOI: 10.1002/cbic.200900575

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      Be selective to simplify: An 15N-label is selectively incorporated into the tryptophan side chains of a large protein and a simplified [1H,15N]-TROSY HSQC spectrum is obtained without the need for deuteration.

    6. C5-Functionalized LNA: Unparalleled Hybridization Properties and Enzymatic Stability (pages 2740–2743)

      Michael E. Østergaard, Pawan Kumar, Bharat Baral, Daniel J. Raible, T. Santhosh Kumar, Brooke A. Anderson, Dale C. Guenther, Lee Deobald, Andrzej J. Paszczynski, Pawan K. Sharma and Patrick J. Hrdlicka

      Version of Record online: 6 OCT 2009 | DOI: 10.1002/cbic.200900500

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      The best of both worlds: C5-functionalized locked nucleic acids (LNAs) synergistically combine the beneficial features of C5-alkynyl DNAs and conventional antisense LNA—they are straightforward to make and yet exhibit unparalleled thermal affinity toward RNA targets, extraordinary discrimination of singly mismatched RNA strands, and superb stability against degradation by 3′-exonucleases.

  9. Full Papers

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. Corrigendum
    6. News
    7. Minireviews
    8. Highlight
    9. Communications
    10. Full Papers
    11. Book Reviews
    12. Preview
    1. Designed RNAs with Two Peptide-Binding Units as Artificial Templates for Native Chemical Ligation of RNA-Binding Peptides (pages 2745–2752)

      Norimasa Kashiwagi, Kohei Yamashita, Hiroyuki Furuta and Yoshiya Ikawa

      Version of Record online: 15 OCT 2009 | DOI: 10.1002/cbic.200900392

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      RNA templates for chemical peptide ligation were designed by inserting two peptide-binding units into self-folding RNAs (right) derived from naturally occurring RNAs (left). The present work suggests that RNAs with modular 3D structures are suitable as platforms to design templates for chemical peptide ligations.

    2. Inhibition of HSP90 with Pochoximes: SAR and Structure-Based Insights (pages 2753–2759)

      Sofia Barluenga, Jean-Gonzague Fontaine, Cuihua Wang, Kais Aouadi, Ruihong Chen, Kristin Beebe, Len Neckers and Nicolas Winssinger

      Version of Record online: 23 OCT 2009 | DOI: 10.1002/cbic.200900494

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      Potent pochoximes: We generated an extended library of pochoxime inhibitors of heat shock protein 90 and identified a pochoxime that has a cellular efficacy of less than 10 nM. By examining cocrystal structures of pochoximes with human HSP90α, we found that these compounds bind to a different conformation of HSP90 than the closely related radicicol.

    3. Control of Lipase Enantioselectivity by Engineering the Substrate Binding Site and Access Channel (pages 2760–2771)

      Vincent Lafaquière, Sophie Barbe, Sophie Puech-Guenot, David Guieysse, Juan Cortés, Pierre Monsan, Thierry Siméon, Isabelle André and Magali Remaud-Siméon

      Version of Record online: 8 OCT 2009 | DOI: 10.1002/cbic.200900439

      Thumbnail image of graphical abstract

      Engineering enantioselectivity: A semirational engineering approach was successfully used to construct small libraries of mutants of B. cepacia lipase. These mutants were screened for their enantioselectivity towards (R,S) bromophenyl-acetic acid chloro ethyl ester. This led to the fast isolation of several mutants with up to tenfold increased enantioselectivity and 15-fold increased specific activity compared to wild-type enzyme.

    4. A Fragment-Based Approach to Probing Adenosine Recognition Sites by Using Dynamic Combinatorial Chemistry (pages 2772–2779)

      Duncan E. Scott, Gwen J. Dawes, Michiyo Ando, Chris Abell and Alessio Ciulli

      Version of Record online: 13 OCT 2009 | DOI: 10.1002/cbic.200900537

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      A new strategy for targeting adenosine recognition sites on enzymes is reported. We demonstrate a proof-of-concept for the use of 5′-deoxy-5′-thioadenosine as a noncovalent anchor fragment in dynamic combinatorial libraries templated by Mycobacterium tuberculosis pantothenate synthetase. A benzyl disulfide derivative was identified and optimised upon structural and binding studies of protein–ligand complexes.

    5. Chaperone Activity of Bicyclic Nojirimycin Analogues for Gaucher Mutations in Comparison with N-(n-nonyl)Deoxynojirimycin (pages 2780–2792)

      Zhuo Luan, Katsumi Higaki, Matilde Aguilar-Moncayo, Haruaki Ninomiya, Kousaku Ohno, M. Isabel García-Moreno, Carmen Ortiz Mellet, José M. García Fernández and Yoshiyuki Suzuki

      Version of Record online: 14 OCT 2009 | DOI: 10.1002/cbic.200900442

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      Bicycles for Gaucher disease: Bicyclic nojirimycin analogues of the sp2-iminosugar family behaved as very selective competitive inhibitors of human lysosomal acid β-glucosidase and proved to be more potent chemical chaperones than N-nonylnojirimycin (NN-DNJ) for several mutations related to Gaucher disease (GD). The results suggest that these compounds are promising candidates for clinical treatment of GD patients, especially for neuronopathic forms of the disease.

    6. Amphiphilic Counterion Activators for DNA: Stimuli-Responsive Cation Transporters and Biosensors in Bulk and Lipid Bilayer Membranes (pages 2793–2799)

      Toshihide Takeuchi, Valentina Bagnacani, Francesco Sansone and Stefan Matile

      Version of Record online: 2 OCT 2009 | DOI: 10.1002/cbic.200900512

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      Not hydrophilic or lipophilic, but both: Complete charge inversion from counterion-activated cell-penetrating peptides affords “biphilic” DNA that is adaptable to any environment, can move across membranes, can transport cations, detect enzyme activity (e.g., phytase) and act as biosensor for different analytes (e.g., phytate).

  10. Book Reviews

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. Corrigendum
    6. News
    7. Minireviews
    8. Highlight
    9. Communications
    10. Full Papers
    11. Book Reviews
    12. Preview
    1. Classics in Spectroscopy: Isolation and Structure Elucidation of Natural Products. By Stefan Berger and Dieter Sicker. (pages 2800–2801)

      Stefan Schulz

      Version of Record online: 17 NOV 2009 | DOI: 10.1002/cbic.200900650

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      Wiley-VCH, Weinheim 2009, XIV+645 pp., softcover € 79.00.—ISBN 978-3-527-32516-0

    2. Epigenetic Targets in Drug Discovery. Edited by Wolfgang Sippl and Manfred Jung. (page 2801)

      Albert Jeltsch

      Version of Record online: 17 NOV 2009 | DOI: 10.1002/cbic.200900556

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      Wiley-VCH, Weinheim 2009, 297 pp., hardcover € 110.00.—ISBN 978-3-527-32355-5

    3. Methods in Molecular Biology, Vol. 515: Viral Applications of Green Fluorescent Protein, Methods and Protocols. Edited by Barry W. Hicks. (pages 2801–2802)

      Johannes Schmid

      Version of Record online: 17 NOV 2009 | DOI: 10.1002/cbic.200900506

      Humana Press, Totowa 2009, XI+357 pp., hardcover $ 109.00.—ISBN 978-1-934115-87-9

    4. Methods in Molecular Biology, Vol. 540: Riboswitches: Methods and Protocols. Edited by Alexander Serganov. (pages 2802–2803)

      Atsushi Ogawa

      Version of Record online: 17 NOV 2009 | DOI: 10.1002/cbic.200900519

      Humana Press 2009, XI+366 pp., hardcover $ 110.00.—ISBN 978-1-934115-88-6

  11. Preview

    1. Top of page
    2. Cover Picture
    3. Inside Cover
    4. Graphical Abstract
    5. Corrigendum
    6. News
    7. Minireviews
    8. Highlight
    9. Communications
    10. Full Papers
    11. Book Reviews
    12. Preview
    1. Preview: ChemBioChem 18/2009 (page 2807)

      Version of Record online: 17 NOV 2009 | DOI: 10.1002/cbic.200990081

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