ChemBioChem

Cover image for Vol. 9 Issue 13

September 1, 2008

Volume 9, Issue 13

Pages 2017–2166

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Communications
    7. Full Papers
    8. Web Review
    9. Book Reviews
    10. Preview
    1. Cover Picture: 8-pCPT-2′-O-Me-cAMP-AM: An Improved Epac-Selective cAMP Analogue (ChemBioChem 13/2008) (page 2017)

      Marjolein J. Vliem, Bas Ponsioen, Frank Schwede, Willem-Jan Pannekoek, Jurgen Riedl, Matthijs R. H. Kooistra, Kees Jalink, Hans-Gottfried Genieser, Johannes L. Bos and Holger Rehmann

      Article first published online: 27 AUG 2008 | DOI: 10.1002/cbic.200890049

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      The cover picture shows the chemical structure of an acetoxymethyl ester of 8-pCPT-2′-O-Me-cAMP (007-AM). 007-AM can pass cell membranes efficiently and is hydrolysed inside the cell by esterases to release the biologically active compound 8-pCPT-2′-O-Me-cAMP (007). Due to its low membrane permeability 007 accumulates inside the cell, where it activates the cAMP receptor protein Epac. The inactive conformation of Epac is shown on the left, with the regulatory region in light blue and the catalytic region in dark blue. Binding of cAMP or 007 to Epac leads to a repositioning of the regulatory region, which allows the substrate protein Rap (yellow) to bind and become activated. Activated Rap causes several biological effects, such as the spreading of cells, shown here for A549-B14 cells. For more information see the article by J. L. Bos, H. Rehmann et al. on p. 2052 ff. (Images of cells were kindly provided by Dr. Sarah Ross).

  2. Graphical Abstract

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Communications
    7. Full Papers
    8. Web Review
    9. Book Reviews
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    1. Graphical Abstract: ChemBioChem 13/2008 (pages 2019–2025)

      Article first published online: 27 AUG 2008 | DOI: 10.1002/cbic.200890050

  3. News

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

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Communications
    7. Full Papers
    8. Web Review
    9. Book Reviews
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    1. Split-Ubiquitin and the Split-Protein Sensors: Chessman for the Endgame (pages 2029–2038)

      Judith Müller and Nils Johnsson

      Article first published online: 1 AUG 2008 | DOI: 10.1002/cbic.200800190

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      Split-protein sensors are increasingly used as analytical tools to identify, measure, and manipulate protein–protein interactions in living cells. By using split-ubiquitin as a representative example, their general and their specific properties as well as their diverse applications in proteomics, cell biology, and synthetic biology are discussed.

    2. Signal Transducers and Activators of Transcription as Targets for Small Organic Molecules (pages 2039–2044)

      Thorsten Berg

      Article first published online: 1 AUG 2008 | DOI: 10.1002/cbic.200800274

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      Targeting transcription factors is one of the emerging challenges in the field of chemical biology. A subgroup of transcription factors referred to as signal transducers and activators of transcription (STATs) has received particular attention because of both their relevance for human disease and the discoveries of a number of potent small-molecule inhibitors, both of which are covered in this review.

  5. Communications

    1. Top of page
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    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Communications
    7. Full Papers
    8. Web Review
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    1. Enhanced Glycosylation with Mutants of Endohexosaminidase A (Endo A) (pages 2045–2051)

      Christoph D. Heidecke, Zhenlian Ling, Neil C. Bruce, James W. B. Moir, Thomas B. Parsons and Antony J. Fairbanks

      Article first published online: 1 AUG 2008 | DOI: 10.1002/cbic.200800214

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      The big make over: Replacement of the key Glu173 residue of Endo A by either glutamine or histidine produces mutant enzymes for which hydrolytic activity has either been eliminated, or significantly curtailed, yet which still effect transglycosylation of acceptor substrates by the use of oxazolines as glycosyl donors. The E173H histidine mutant was demonstrated to be more effective than wild-type Endo A for the production of a single homogenous glycoform of ribonuclease B (see scheme).

    2. 8-pCPT-2′-O-Me-cAMP-AM: An Improved Epac-Selective cAMP Analogue (pages 2052–2054)

      Marjolein J. Vliem, Bas Ponsioen, Frank Schwede, Willem-Jan Pannekoek, Jurgen Riedl, Matthijs R. H. Kooistra, Kees Jalink, Hans-Gottfried Genieser, Johannes L. Bos and Holger Rehmann

      Article first published online: 16 JUL 2008 | DOI: 10.1002/cbic.200800216

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      An Epac-selective precursor with high potency: Signalling by the second messenger cAMP is mediated by its receptor proteins protein kinase A (PKA), Epac and cyclic-nucleotide-regulated ion channels. This manuscript describes the synthesis and biological characterisation of a precursor that selectively activates Epac and that is 100 to 1000 times more efficient under biological conditions than the parental compound.

    3. Two Lysine Residues are Responsible for the Enzymatic Activities of Indole Prenyltransferases from Fungi (pages 2055–2058)

      Edyta Stec, Nicola Steffan, Anika Kremer, Huixi Zou, Xiaodong Zheng and Shu-Ming Li

      Article first published online: 1 AUG 2008 | DOI: 10.1002/cbic.200800237

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      Basic more important: The importance of two lysine residues (shown in red in the figure) in the catalysis of indole prenyltransferases from fungi was demonstrated by site-directed mutagenesis with FgaPT2, FtmPT1 and 7-DMATS from Aspergillus fumigatus. Mutation of a conserved arginine (green) and aspartate (blue) resulted in only a slight decrease in enzymatic activity.

    4. FtmPT2, an N-Prenyltransferase from Aspergillus fumigatus, Catalyses the Last Step in the Biosynthesis of Fumitremorgin B (pages 2059–2063)

      Alexander Grundmann, Tatyana Kuznetsova, Shamil Sh. Afiyatullov and Shu-Ming Li

      Article first published online: 5 AUG 2008 | DOI: 10.1002/cbic.200800240

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      Last, but not least: The ftmPT2 gene, which was identified in a biosynthetic gene cluster for fumitremorgins in Aspergillus fumigatus, was over-expressed in Saccharomyces cerevisiae. The purified soluble dimeric His6–FtmPT2 was characterised biochemically. Structure elucidation of the enzymatic product showed that FtmPT2 catalyses the prenylation of 12,13-dihydroxyfumitremorgin C in the presence of dimethylallyl diphosphate at position N1 of the indole ring and so functions as an N-prenyltransferase (see scheme).

    5. Chemoenzymatic Total Synthesis of the Antiproliferative Polyketide (+)-(R)-Aureothin (pages 2064–2066)

      Martina Werneburg and Christian Hertweck 

      Article first published online: 8 AUG 2008 | DOI: 10.1002/cbic.200800301

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      Enzymaticaurification: The first asymmetric synthesis of the antiproliferative and antifungal pyrone metabolite (+)-(R)-aureothin (1) from Streptomyces thioluteus was completed by taking advantage of synergy of synthetic and enzymatic transformations. Synthetic vinyl iodide 14 was regioselectively methylated by AurI prior to asymmetric heterocyclization catalyzed by the bifunctional monooxygenase AurH and Stille coupling.

    6. Ultrasensitive Detection of DNA by PNA and Nanoparticle-Enhanced Surface Plasmon Resonance Imaging (pages 2067–2070)

      Roberta D'Agata, Roberto Corradini, Giuseppe Grasso, Rosangela Marchelli and Giuseppe Spoto 

      Article first published online: 4 AUG 2008 | DOI: 10.1002/cbic.200800310

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      Femtomolar single-base mismatch discrimination: A nanoparticle-enhanced surface plasmon resonance imaging method for ultrasensitive detection of the selective hybridization between a peptide nucleic acid (PNA) oligomer and its complementary single-stranded DNA target is described. The method allows a 1 fM sensitivity in single-base mismatch discrimination with only 150 zeptomoles of the target molecules.

    7. Click Chemistry as an Efficient Method for Preparing a Sensitive DNA Probe for Photochemical Ligation (pages 2071–2074)

      Takehiro Ami and Kenzo Fujimoto

      Article first published online: 30 JUL 2008 | DOI: 10.1002/cbic.200800316

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      Speed of light: We report a new photosensitive probe that takes advantage of the electronic structural changes associated with the formation of triazole rings in CuI-catalyzed Huisgen 1,3-dipolar cycloadditions between organic azides and terminal alkynes. We have succeeded in performing photoligation on a timescale of seconds. We also report an efficient procedure using photochemical ligation for the preparation of a DNA probe for quick SNP typing.

    8. G-Quadruplex Formation Interferes with P1 Helix Formation in the RNA Component of Telomerase hTERC (pages 2075–2079)

      Julien Gros, Aurore Guédin, Jean-Louis Mergny and Laurent Lacroix

      Article first published online: 6 AUG 2008 | DOI: 10.1002/cbic.200800300

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      G4-RNA: We report here the formation of a RNA–guanine quadruplex structure in the 5′ part of hTERC, and we demonstrate on a model system that the interaction of this 5′ part with a guanine quadruplex ligand prevents P1 helix formation.

  6. Full Papers

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Communications
    7. Full Papers
    8. Web Review
    9. Book Reviews
    10. Preview
    1. Mechanism of Binding of Fluoroquinolones to the Quinolone Resistance-Determining Region of DNA Gyrase: Towards an Understanding of the Molecular Basis of Quinolone Resistance (pages 2081–2086)

      Sergio Madurga, Javier Sánchez-Céspedes, Ignasi Belda, Jordi Vila and Ernest Giralt

      Article first published online: 1 AUG 2008 | DOI: 10.1002/cbic.200800041

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      The mode of binding of ciprofloxacin, levofloxacin, and moxifloxacin fluoroquinolones to DNA gyrase over the surface of the “quinolone resistance-determining region” of GyrA has been investigated in a study at the atomic level of the resistance mechanism associated with gyrA mutations most commonly found in E. coli fluoroquinolone-resistant strains. Important roles were found for Asp87, Ser83, and Arg121 in the DNA gyrase.

    2. A Macrophage Cell Model for Selective Metalloproteinase Inhibitor Design (pages 2087–2095)

      Faith E. Jacobsen , Matthew W. Buczynski , Edward A. Dennis  and Seth M. Cohen

      Article first published online: 30 JUL 2008 | DOI: 10.1002/cbic.200800148

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      Selective zinc chelation: A cell-based screening method using the RAW264.7 macrophage cell line to compare the relative activities of zinc, heme iron, and non-heme iron enzymes in the presence of zinc-dependent matrix metalloproteinase inhibitors is presented. With this model we identified two nitrogen donor compounds—2,2′-dipyridylamine and triazacyclononane—as the most selective zinc-binding groups for zinc metalloenzyme inhibitor development.

    3. Probing the Compatibility of Type II Ketosynthase–Carrier Protein Partners (pages 2096–2103)

      Andrew S. Worthington, Gene H. Hur, Jordan L. Meier, Qian Cheng, Bradley S. Moore and Michael D. Burkart

      Article first published online: 30 JUL 2008 | DOI: 10.1002/cbic.200800198

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      Playing nicely: Post-translational modification of the acyl carrier protein with a panel of functionalized CoA molecules affords activated species that are capable of site-directed crosslinking with ketosynthase enzymes. This method provides a handle to probe substrate tolerance and protein–protein interactions within both natural and combinatorial biosynthetic systems.

    4. Switch-Peptides: Design and Characterization of Controllable Super-Amyloid-Forming Host–Guest Peptides as Tools for Identifying Anti-Amyloid Agents (pages 2104–2112)

      Marie-Stéphanie Camus, Sonia Dos Santos, Arunan Chandravarkar, Bhubaneswar Mandal, Adrian W. Schmid, Gabriele Tuchscherer, Manfred Mutter and Hilal A. Lashuel

      Article first published online: 5 AUG 2008 | DOI: 10.1002/cbic.200800245

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      Fibrillization switches: The design and characterization of host–guest switch peptides that can be used for in vitro mechanistic and screening studies aimed at discovering aggregation inhibitors that target highly amyloidogenic sequences are described.

    5. Peptide-Grafted Nanodiamonds: Preparation, Cytotoxicity and Uptake in Cells (pages 2113–2119)

      Stéphanie Vial, Christelle Mansuy , Sandrine Sagan, Theano Irinopoulou, Fabienne Burlina, Jean-Paul Boudou, Gérard Chassaing and Solange Lavielle

      Article first published online: 1 AUG 2008 | DOI: 10.1002/cbic.200800247

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      A girl's best friend: Nanodiamonds (cNDs, ≤35 nm) were coated by silanisation or with a polyelectrolyte and grafted with a fluorescent thiolated peptide through a maleimido function to give aqueous colloidal suspensions that were stable for months. These substituted NDs were not cytotoxic for CHO cells. Their capacity to enter CHO cells (see figure) and their localisation were ascertained by labelling the nucleus and actin, and then examining the cells by confocal, reflected light and fluorescence microscopy.

    6. Site-Selective Blocking of PCR by a Caged Nucleotide Leading to Direct Creation of Desired Sticky Ends in The Products (pages 2120–2126)

      Keita Tanaka, Hitoshi Katada, Narumi Shigi, Akinori Kuzuya and Makoto Komiyama

      Article first published online: 7 AUG 2008 | DOI: 10.1002/cbic.200800285

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      Widening the scope of DNA manipulation: Caged thymine units were incorporated into PCR primers to terminate the polymerase reaction at a desired position. After photoremoval of the protecting groups, sticky ends of desired length and sequence had been directly formed on the PCR product encoding the GFP gene. These were successfully ligated with a plasmid vector and used to transform E. coli.

    7. Supramolecular Domains in Mixed Peptide Self-Assembled Monolayers on Gold Nanoparticles (pages 2127–2134)

      Laurence Duchesne, Geoff Wells, David G. Fernig, Sarah A. Harris and Raphaël Lévy

      Article first published online: 12 AUG 2008 | DOI: 10.1002/cbic.200800326

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      Self-organization: A strategy based on chemical cross-linking is introduced to probe proximity between functional peptides embedded in a mixed self-assembled monolayer at the surface of a gold nanoparticle. The results indicate that the peptides are not randomly distributed at the surface of the nanoparticle, but rather self-organize into supramolecular domains.

    8. Solution Structure of a Functional Biomimetic and Mechanistic Implications for Nickel Superoxide Dismutases (pages 2135–2146)

      Matthias Schmidt, Stefan Zahn, Michela Carella, Oliver Ohlenschläger, Matthias Görlach, Erika Kothe and James Weston

      Article first published online: 8 AUG 2008 | DOI: 10.1002/cbic.200800017

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      The bare essentials: The 3D solution structure (top) of a functional peptide-based NiSOD biomimetic reveals a stable preformed binding site for NiII. The SOD activity is compared to enzymatic systems, and mechanistic consequences are discussed. Selected modifications allowed a minimal functional motif (bottom) to be identified.

    9. Synthesis and Characterization of a Long, Rigid Photoswitchable Cross-Linker for Promoting Peptide and Protein Conformational Change (pages 2147–2154)

      Fuzhong Zhang, Oleg Sadovski and G. Andrew Woolley

      Article first published online: 27 AUG 2008 | DOI: 10.1002/cbic.200800196

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      Making ends meet. A long, rigid, water-soluble, thiol-reactive cross-linker, 3,3′-diazene-1,2-diylbis{6-[2-sulfonato-4-(chloroacetylamino)phenylethynyl]benzene sulfonic acid} (DDPBA), has been synthesized to produce an azobenzene photoswitch that undergoes a large end-to-end distance change upon isomerization.

  7. Web Review

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  8. Book Reviews

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  9. Preview

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      Preview: ChemBioChem 14/2008 (page 2166)

      Article first published online: 27 AUG 2008 | DOI: 10.1002/cbic.200890052

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