ChemBioChem

Cover image for ChemBioChem

November 23, 2007

Volume 8, Issue 17

Pages 2021–2170

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Communications
    6. Full Papers
    7. Conference Report
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    1. Cover Picture: Identification of a Potent Inhibitor of Human Dual-Specific Phosphatase, VHR, from Computer-Aided and NMR-Based Screening to Cellular Effects (ChemBioChem 17/2007) (page 2021)

      Zhe Shi, Sartaj Tabassum, Wei Jiang, Jiahai Zhang, Suvigya Mathur, Jihui Wu and Yunyu Shi

      Version of Record online: 13 NOV 2007 | DOI: 10.1002/cbic.200790060

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      The cover picture shows a potent and competitive inhibitor, (glucosamine-aminoethoxy)triphenyltin (GATPT), of the dual-specific human vaccinia H1-related phosphatase (VHR). This inhibitor was successfully identified from a compound library, by combining a virtual- and NMR-based ligand-screening strategy. The putative binding mode provides structural insights into the ligand-binding mechanism. These results demonstrate that this screening strategy can be employed in the early stage of drug discovery to find inhibitors with novel structures and also to gain insights into their binding mode. The cellular effects of GATPT on phosphorylation of ERK and JNK and cell-cycle progression are reported. Details of the screening, modeling, and functional experiments are in the article by Y. Shi, J. Wu et al. on p. 2092 ff.

  2. Graphical Abstract

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    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Communications
    6. Full Papers
    7. Conference Report
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  3. News

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    3. Graphical Abstract
    4. News
    5. Communications
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  4. Communications

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    3. Graphical Abstract
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    1. A New Inorganic Photolabile Protecting Group for Highly Efficient Visible Light GABA Uncaging (pages 2035–2038)

      Leonardo Zayat, María G. Noval, Julieta Campi, Cecilia I. Calero, Daniel J. Calvo and Roberto Etchenique

      Version of Record online: 15 OCT 2007 | DOI: 10.1002/cbic.200700354

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      Inhibiting with visible light. An inorganic-based caged compound of the inhibitory neurotransmitter, γ-amino butyric acid (GABA), was prepared and photolysed by light at 450 nm with the highest uncaging quantum yield reported to date. GABA ion channels were activated by irradiation in a biological preparation by using this caged compound. (Image courtesy of the CNS Forum http://www.cnsforum.com)

    2. A Binary Deoxyribozyme for Nucleic Acid Analysis (pages 2039–2042)

      Dmitry M. Kolpashchikov

      Version of Record online: 8 OCT 2007 | DOI: 10.1002/cbic.200700384

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      A binary star is born. Two unmodified DNA strands were found to form a catalytically active core upon hybridization to abutting positions of a DNA analyte (see figure). The DNAzyme cleaved a fluorophore- and quencher-labeled substrate; this resulted in increased fluorescence of the solution.

    3. You have full text access to this OnlineOpen article
      A Novel Mycolactone Toxin Obtained by Biosynthetic Engineering (pages 2043–2047)

      Hui Hong, Tim Stinear, Jessica Porter, Caroline Demangel and Peter F. Leadlay

      Version of Record online: 28 SEP 2007 | DOI: 10.1002/cbic.200700411

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      A novel structural variant of the mycobacterial polyketide toxin mycolactone has been obtained by cloning a P450 hydroxylase gene from a related strain. This technique increases the range of available mycolactones for studies on the mode of action of the toxin.

    4. Peptide Borono Lectins (PBLs): A New Tool for Glycomics and Cancer Diagnostics (pages 2048–2051)

      Yuejiao Zou, Dana L. Broughton, Kevin L. Bicker, Paul R. Thompson and John J. Lavigne

      Version of Record online: 10 OCT 2007 | DOI: 10.1002/cbic.200700221

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      Peptide borono lectins (PBLs) have been synthesized and shown to bind glycoproteins dependant on the glycoprotein and PBL structures. The binding is reversible and it has been demonstrated that both selective and cross-reactive PBLs can be identified. The potential utility of these PBLs as a cancer diagnostic has been demonstrated.

    5. Isolation of DNA Aptamers for CDP-Ribitol Synthase, and Characterization of Their Inhibitory and Structural Properties (pages 2052–2057)

      Abdellah Allali-Hassani, Mark P. Pereira, Naveen K. Navani, Eric D. Brown and Yingfu Li

      Version of Record online: 11 OCT 2007 | DOI: 10.1002/cbic.200700257

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      Two birds with one stone: Four DNA aptamers were isolated for Bcs1, a bifunctional enzyme that catalyzes both the reduction of ribulose 5-phosphate by using NADPH and cytidylyltransfer by using CTP. The inhibitory effects of these aptamers towards Bcs1 and their secondary structural properties were investigated (see scheme).

    6. Targeted Degradation of the Aryl Hydrocarbon Receptor by the PROTAC Approach: A Useful Chemical Genetic Tool (pages 2058–2062)

      Hyosung Lee, Dinesh Puppala, Eun-Young Choi, Hollie Swanson and Kyung-Bo Kim

      Version of Record online: 28 SEP 2007 | DOI: 10.1002/cbic.200700438

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      License to degrade. A chimeric small molecule or PROTAC (PROteolysis TArgeting Chimera) based on the chemopreventive natural product apigenin was developed (see scheme). The molecule was shown to target the aryl hydrocarbon receptor (AHR) for degradation by the proteasome.

    7. Tuning the Membrane Selectivity of Antimicrobial Peptides by Using Multivalent Design (pages 2063–2065)

      Zhigang Liu, Anne W. Young, Po Hu, Amanda J. Rice, Chunhui Zhou, Yingkai Zhang and Neville R. Kallenbach

      Version of Record online: 8 OCT 2007 | DOI: 10.1002/cbic.200700502

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      Multivalent design of antibacterials. Cationic charge and lipophilicity are major determinants of antibacterial activity in antimicrobial peptides that contain a high population of the amino acids Trp (W) and Arg (R). We show here that multivalent display of the RW dipeptide pharmacophore enhances antibacterial activity and membrane selectivity.

  5. Full Papers

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    3. Graphical Abstract
    4. News
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    1. Optimal Conditions for Labelling of 3T3 Fibroblasts with Magnetoliposomes without Affecting Cellular Viability (pages 2067–2077)

      Stefaan J. H. Soenen, Johan Baert and Marcel De Cuyper

      Version of Record online: 17 OCT 2007 | DOI: 10.1002/cbic.200700327

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      Positively incorporated. In this work, the cellular uptake of cationic magnetoliposomes was investigated. The effect of incubation time, the cationic lipid type and its concentration in the magnetoliposome (ML) coating on uptake efficiency and cell viability were examined (see figure). Cytotoxicity was related to the lipid coating only. Lysosomal labelling was observed, and optimal uptake was found to occur with 3.33 % DSTAP-containing particles.

    2. Macrocyclic Statine-Based Inhibitors of BACE-1 (pages 2078–2091)

      Alessandra Barazza, Marion Götz, Sergio A. Cadamuro, Peter Goettig, Michael Willem, Holger Steuber, Tanja Kohler, Anja Jestel, Peter Reinemer, Christian Renner, Wolfram Bode and Luis Moroder

      Version of Record online: 26 OCT 2007 | DOI: 10.1002/cbic.200700383

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      Hitting BACE. A 23-membered macrocyclic inhibitor of BACE-1 containing statine as a transition state analogue in the ring structure (green) was found to bind with the peptide backbone in an extended conformation to the active-site cleft, in a manner almost identical to that of a substrate-derived linear hydroxyethylene-octapeptide (yellow), without steric clashes with the flap domain.

    3. Identification of a Potent Inhibitor of Human Dual-Specific Phosphatase, VHR, from Computer-Aided and NMR-Based Screening to Cellular Effects (pages 2092–2099)

      Zhe Shi, Sartaj Tabassum, Wei Jiang, Jiahai Zhang, Suvigya Mathur, Jihui Wu and Yunyu Shi

      Version of Record online: 12 OCT 2007 | DOI: 10.1002/cbic.200700397

      Thumbnail image of graphical abstract

      Combining form and function. By combining a virtual and NMR-based ligand-screening strategy a new potent and competitive inhibitor, (glucosamine-aminoethoxy)triphenyltin (GATPT), of the dual-specific human vaccinia H1-related phosphatase (VHR) was successfully identified; the figure illustrates the molecular model of GATPT binding to VHR. The cellular effects of GATPT are reported.

    4. Tunable Photoactivation of a Post-translationally Modified Signaling Protein and its Unmodified Counterpart in Live Cells (pages 2100–2105)

      Michael E. Hahn, Jean-Philippe Pellois, Miquel Vila-Perelló and Tom W. Muir

      Version of Record online: 28 SEP 2007 | DOI: 10.1002/cbic.200700404

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      Strike a pose… Expressed protein ligation was used to prepare caged analogues of the signaling protein Smad2 (see illustration). The function and fluorescence of the analogues could be photocontrolled in a correlated fashion. This strategy permitted the titration of the cellular levels of active phosphorylated Smad2 in its biologically relevant, full-length form.

    5. Synthesis of 5-(1,2,3-Triazol-4-yl)-2′-deoxyuridines by a Click Chemistry Approach: Stacking of Triazoles in the Major Groove Gives Increased Nucleic Acid Duplex Stability (pages 2106–2116)

      Petr Kočalka, Nicolai K. Andersen, Frank Jensen and Poul Nielsen

      Version of Record online: 30 OCT 2007 | DOI: 10.1002/cbic.200700410

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      Click into place. Three modified 2′-deoxyuridines with either unsubstituted or 1-phenyl-/1-benzyl-substituted triazoles in the 5-position were synthesised by click chemistry and introduced into oligonucleotides. With consecutive incorporations, efficient stacking of the triazoles in the major groove was observed (see scheme). While single modifications led to decreased duplex stability, the stacking of four consecutive modifications led to significantly enhanced thermal stability of DNA–RNA duplexes.

    6. Glycochips from Polyanionic Glycopolymers as Tools for Detecting Shiga Toxins (pages 2117–2124)

      Hirotaka Uzawa, Hiroki Ito, Paola Neri, Hiroshi Mori and Yoshihiro Nishida

      Version of Record online: 11 OCT 2007 | DOI: 10.1002/cbic.200700439

      Thumbnail image of graphical abstract

      Layer upon layer… An alternating layer-by-layer adsorption methodology was applied to the assembly of glycochips by using synthetic polyanionic glycopolymers (see structural representation). Three glycochips carrying globobioside, β-lactoside, or α-D-mannoside were prepared. By using surface plasmon resonance the Gb2 glycochips were found to be useful devices for the detection of and discrimination between Shiga toxin homologues, Stx-1 and Stx-2.

    7. Specificity Fingerprinting of Retaining β-1,4-Glycanases in the Cellulomonas fimi Secretome Using Two Fluorescent Mechanism-Based Probes (pages 2125–2132)

      Omid Hekmat, Christine Florizone, Young-Wan Kim, Lindsay D. Eltis, R. Antony J. Warren and Stephen G. Withers

      Version of Record online: 19 OCT 2007 | DOI: 10.1002/cbic.200700481

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      Glycosidases see the light. Two spectrally nonoverlapping fluorescent, mechanism-based probes containing different binding elements for retaining endo-cellulases and endo-xylanases were prepared and used to obtain a specificity fingerprint of glycanases in the biomass-degrading Cellulomonas fimi secretome under induction by different polyglycan growth substrates. Such probes are useful tools for rapid surveying of complements of cellulases and xylanases produced by biomass-degrading organisms.

    8. Study of Modification Pattern–RNAi Activity Relationships by Using siRNAs Modified with 4′-Thioribonucleosides (pages 2133–2138)

      Shuichi Hoshika, Noriaki Minakawa, Aki Shionoya, Keiko Imada, Naoki Ogawa and Akira Matsuda

      Version of Record online: 8 OCT 2007 | DOI: 10.1002/cbic.200700342

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      Silencing genes. A detailed study of modification pattern–RNAi activity relationships by using siRNAs that was modified with 4′-thioribonucleosides afforded an effective modification pattern against two target genes in three different cell lines. Our findings also indicate the significance of target sequences and cell lines when RNAi activity is compared with that of the unmodified siRNA.

    9. Mutasynthesis-Derived Myxalamids and Origin of the Isobutyryl-CoA Starter Unit of Myxalamid B (pages 2139–2144)

      Helge B. Bode, Peter Meiser, Thorsten Klefisch, Niña Socorro d. J. Cortina, Daniel Krug, Anke Göhring, Gertrud Schwär, Taifo Mahmud, Yasser A. Elnakady and Rolf Müller

      Version of Record online: 22 OCT 2007 | DOI: 10.1002/cbic.200700401

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      Nine new myxalamids have been obtained from the myxobacteria Myxococcus xanthus and Stigmatella aurantiaca by mutasynthesis. Moreover, feeding experiments with S. aurantiaca have identified iso-odd fatty acids as a major source of the starter unit isobutyryl-CoA (see myxalamid B in scheme), which is normally derived from valine.

    10. Glycosynthase Activity of Geobacillus stearothermophilus GH52 β-Xylosidase: Efficient Synthesis of Xylooligosaccharides from α-D-Xylopyranosyl Fluoride through a Conjugated Reaction (pages 2145–2151)

      Alon Ben-David, Tsafrir Bravman, Yael S. Balazs, Mirjam Czjzek, Dietmar Schomburg, Gil Shoham and Yuval Shoham

      Version of Record online: 22 OCT 2007 | DOI: 10.1002/cbic.200700414

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      From mono to oligo: A novel β-xylosidase (GH52) glycosynthase catalyzes the self condensation of α-D-xylopyranosyl fluoride to afford α-D-xylobiosyl fluoride. When combined with a β-xylanase (GH10) glycosynthase, high molecular weight xylooligomers (degree of polymerization over 100) were readily obtained from the affordable α-D-xylopyranosyl fluoride in aqueous solution (see figure).

    11. Insight Into the Kinetic of Amyloid β (1–42) Peptide Self-Aggregation: Elucidation of Inhibitors’ Mechanism of Action (pages 2152–2161)

      Manuela Bartolini, Carlo Bertucci, Maria Laura Bolognesi, Andrea Cavalli, Carlo Melchiorre and Vincenza Andrisano

      Version of Record online: 15 OCT 2007 | DOI: 10.1002/cbic.200700427

      Thumbnail image of graphical abstract

      Slowing the plaques. A reliable and reproducible in-solution assay that is based on circular dichroism (CD) spectroscopy was optimized to monitor the amyloid β (1–42) (Aβ42) initial secondary-structure transition. A CD kinetic study in the presence of known inhibitors revealed some clues to understanding the molecular events involved in amyloid β (Aβ) aggregation.

  6. Conference Report

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    2. Cover Picture
    3. Graphical Abstract
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    5. Communications
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  7. Preview

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    1. You have free access to this content
      Preview: ChemBioChem 18/2007 (page 2170)

      Version of Record online: 13 NOV 2007 | DOI: 10.1002/cbic.200790063

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