ChemBioChem

Cover image for Vol. 9 Issue 3

February 15, 2008

Volume 9, Issue 3

Pages 337–474

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. Corrigendum
    5. News
    6. Highlight
    7. Communications
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    1. Cover Picture: Indoloquinolizidine Derivatives as Novel and Potent Apoptosis Inducers and Cell-Cycle Blockers (ChemBioChem 3/2008) (page 337)

      Frank Wehner, Andrea Nören-Müller, Oliver Müller, Ivan Reis-Corrêa Jr., Athanassios Giannis and Herbert Waldmann

      Version of Record online: 8 FEB 2008 | DOI: 10.1002/cbic.200890004

      Thumbnail image of graphical abstract

      The cover picture shows an indoloquinolizidine derivative that has been identified as a potent cell-death-inducing (apoptosis) agent, after the screening of 11 000 natural-product-derived and -inspired compounds in three human tumour cell lines. The background shows the stark white branches of a dead tree in front of the green of a living one, while the blue sea in the distance symbolises (unreachable) eternity. FACS analysis indicated that the derivative shown is one of seven compounds that are able to arrest cells in the G2M phase of the cell cycle. For more details see the article by F. Wehner et al. on p. 401 ff.

  2. Graphical Abstract

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    3. Graphical Abstract
    4. Corrigendum
    5. News
    6. Highlight
    7. Communications
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  3. Corrigendum

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    2. Cover Picture
    3. Graphical Abstract
    4. Corrigendum
    5. News
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      Foldamers: Structure, Properties, and Applications (page 345)

      Kent Kirshenbaum

      Version of Record online: 8 FEB 2008 | DOI: 10.1002/cbic.200890006

      This article corrects:

      Foldamers: Structure, Properties, and Applications. Edited by Stefan Hecht and Ivan Huc.

      Vol. 9, Issue 1, 157–158, Version of Record online: 19 DEC 2007

  4. News

    1. Top of page
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    3. Graphical Abstract
    4. Corrigendum
    5. News
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  5. Highlight

    1. Top of page
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    3. Graphical Abstract
    4. Corrigendum
    5. News
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    1. Functional Reassembly of Split Enzymes On-Site: A Novel Approach for Highly Sequence-Specific Targeted DNA Methylation (pages 351–353)

      Antal Kiss and Elmar Weinhold

      Version of Record online: 11 JAN 2008 | DOI: 10.1002/cbic.200700662

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      Assembling the tool on the spot. Split enzymes need to come together to gain activity. Assembly of an artificially split DNA methyltransferase can be directed to a single 5′-CG-3′ DNA sequence in vivo by fusing both enzyme fragments to zinc finger proteins; this leads to programmable, highly sequence-specific DNA methylation. Such tools hold great promise for selective silencing of genes by targeted methylation of their promoters.

  6. Communications

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    4. Corrigendum
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    1. Light-Switching Excimer Beacon Assays For Ribonuclease H Kinetic Study (pages 355–359)

      Yan Chen, Chaoyong James Yang, Yanrong Wu, Patrick Conlon, Youngmi Kim, Hui Lin and Weihong Tan

      Version of Record online: 7 JAN 2008 | DOI: 10.1002/cbic.200700542

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      We have molecularly engineered light-switching excimer molecular beacons for real-time and sensitive analysis of RNase H activity with a high signal-to-background ratio. This molecular engineering strategy holds great potential for the development of various effective molecular probes for different enzyme-activity studies.

    2. Quinone Replacements for Small Molecule Insulin Mimics (pages 360–362)

      Michael C. Pirrung, Liu Deng, Bo Lin and Nicholas J. G. Webster

      Version of Record online: 29 JAN 2008 | DOI: 10.1002/cbic.200700597

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      Hybrid vigor. A 3-stannylindole was coupled with a 2-bromokojic acid to give an (indolyl)kojic acid that activates the insulin receptor in cell-based assays. This structure represents a hybrid between two Aspergillus natural products, demethylasterriquinone B1 and kojic acid (see figure).

    3. Efficient Asymmetric Synthesis of Chiral Amines by Combining Transaminase and Pyruvate Decarboxylase (pages 363–365)

      Matthias Höhne, Steffen Kühl, Karen Robins and Uwe T. Bornscheuer

      Version of Record online: 21 JAN 2008 | DOI: 10.1002/cbic.200700601

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      Two is better than one (enzyme). The combination of ω-transaminase with pyruvate decarboxylase (PDC) allowed for the efficient asymmetric synthesis of chiral amines, because the unfavorable equilibrium could be shifted by removal of pyruvate by using PDC.

    4. Enzymatic N-terminal Addition of Noncanonical Amino Acids to Peptides and Proteins (pages 366–369)

      Rebecca E. Connor, Konstantin Piatkov, Alexander Varshavsky and David A. Tirrell

      Version of Record online: 18 JAN 2008 | DOI: 10.1002/cbic.200700605

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      Get connected: A chromatographic assay was used to identify ten noncanonical amino acids that can be appended to the N terminus of peptides and proteins by the L,F-transferase of Escherichia coli. A model protein substrate, E. coli dihydrofolate reductase, was modified with p-ethynylphenylalanine and conjugated to azide–biotin and azide–polyethylene glycol–fluorescein probes (see scheme).

    5. Using Fluorous Amino Acids to Modulate the Biological Activity of an Antimicrobial Peptide (pages 370–373)

      Lindsey M. Gottler, Hyang-Yeol Lee, Charles E. Shelburne, Ayyalusamy Ramamoorthy and E. Neil G. Marsh

      Version of Record online: 25 JAN 2008 | DOI: 10.1002/cbic.200700643

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      Leap frog: Antimicrobial peptides based on the structure of the magainin peptides from the African clawed frog have shown great promise as therapeutic agents. However their efficacy in vivo is limited by their susceptibility to proteolysis. We show that incorporating the fluorous amino acid hexafluoroleucine into a magainin analogue (see scheme) dramatically improves stability to proteolysis while retaining biological activity.

    6. Non-Heme Hydroxylase Engineering For Simple Enzymatic Synthesis of L-threo-Hydroxyaspartic Acid (pages 374–376)

      Matthias Strieker, Lars-Oliver Essen, Christopher T. Walsh and Mohamed A. Marahiel

      Version of Record online: 21 JAN 2008 | DOI: 10.1002/cbic.200700557

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      The direct hydroxylation of aliphatic carbon atoms is a challenging task in organic chemistry. Nature's unique ability to solve this problem by using non-heme iron hydroxylases was applied to the stereospecific synthesis of the medically important compound L-threo-hydroxyaspartic acid. We switched the substrate specificity of a hydroxylase (AsnO) from L-asparagine to L-aspartic acid by a simple side chain swap in the substrate binding pocket.

    7. A Voltage-Responding Ion Channel Derived by C-Terminal Modification of Gramicidin A (pages 377–379)

      Philipp Reiß, Loay Al-Momani and Ulrich Koert

      Version of Record online: 25 JAN 2008 | DOI: 10.1002/cbic.200700519

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      Synthetic gates. A positively charged gate was connected to the C terminus of gramicidin A via an ether linkage. A voltage-responding heterodimer channel was formed, which shows a lipid- dependent rectified current behaviour.

  7. Full Papers

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    3. Graphical Abstract
    4. Corrigendum
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    1. Synthesis and Immunological Properties of a Tetrasaccharide Portion of the B Side Chain of Rhamnogalacturonan II (RG-II) (pages 381–388)

      Yu Rao, Therese Buskas, Anathea Albert, Malcolm A. O'Neill, Michael G. Hahn and Geert-Jan Boons

      Version of Record online: 14 JAN 2008 | DOI: 10.1002/cbic.200700501

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      Conformation matters. A tetrasaccharide derived from the B side chain of the plant cell-wall pectic polysaccharide rhamnogalacturonan II (RG-II) was synthesized. Antibodies elicited by a KLH conjugate of the tetrasaccharide recognized RG-II from Arabidopsis thaliana cell wall, but did not recognize RG-II from red wine. This differential recognition was rationalized by the unique conformational properties of the central arabinopyranosyl moiety of the tetrasaccharide and natural RG-IIs.

    2. Comparative Analyses of N-Acylated Homoserine Lactones Reveal Unique Structural Features that Dictate Their Ability to Activate or Inhibit Quorum Sensing (pages 389–400)

      Grant D. Geske, Jennifer C. O'Neill, David M. Miller, Rachel J. Wezeman, Margrith E. Mattmann, Qi Lin and Helen E. Blackwell

      Version of Record online: 25 JAN 2008 | DOI: 10.1002/cbic.200700551

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      Comparison counts. We have delineated key structural features of synthetic N-acylated homoserine lactones (shown in figure) that render these ligands antagonists and agonists of quorum sensing in Gram negative bacteria. These structure–activity relationships were determined through the study of a series of focused combinatorial libraries and provide a foundation on which to design next-generation quorum sensing modulators with improved activities and selectivities.

    3. Indoloquinolizidine Derivatives as Novel and Potent Apoptosis Inducers and Cell-Cycle Blockers (pages 401–405)

      Frank Wehner, Andrea Nören-Müller, Oliver Müller, Ivan Reis-Corrêa Jr., Athanassios Giannis and Herbert Waldmann

      Version of Record online: 11 JAN 2008 | DOI: 10.1002/cbic.200700558

      Thumbnail image of graphical abstract

      A view to a kill: 11 000 natural-product-derived and -inspired compounds were screened for potential apoptosis inducers in three human tumour cell lines. Seven indoloquinolizidine derivatives, one of which is shown in the figure, were identified. These compounds had IC50 values as low as 2 μmol L−1 for inhibiting cell proliferation. Further analysis indicated that these effects were related to an arrest of cells in the G2M phase of the cell cycle.

    4. Rational Protein Design of ThDP-Dependent Enzymes—Engineering Stereoselectivity (pages 406–412)

      Dörte Gocke, Lydia Walter, Ekaterina Gauchenova, Geraldine Kolter, Michael Knoll, Catrine L. Berthold, Gunter Schneider, Jürgen Pleiss, Michael Müller and Martina Pohl

      Version of Record online: 25 JAN 2008 | DOI: 10.1002/cbic.200700598

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      Switching enantiomers: When thiamin diphosphate-dependent enzymes catalyze C[BOND]C bond formation with aldehydes to form 2-hydroxyketones they are usually strictly R selective. Using a structure-guided approach we have identified the molecular reason for their latent inherent S selectivity, which now opens up access to the in silico design of S-selective biocatalysts (see figure).

    5. Monomer Formation and Function of p-Hydroxybenzoate Hydroxylase in Reverse Micelles and in Dimethylsulfoxide/Water Mixtures (pages 413–419)

      Elena V. Kudryashova, Antonie J. W. G. Visser and Willem J. H. van Berkel

      Version of Record online: 4 JAN 2008 | DOI: 10.1002/cbic.200700267

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      Isolation of the monomeric form of PHBH. p-Hydroxybenzoate hydroxylase is a dimeric prototype flavoprotein monooxygenase, but surprisingly little is known about the function of the dimer. Here it is demonstrated that the monomeric form of PHBH is active—indeed, catalytically more efficient than the PHBH dimer—and can be generated by entrapment in reverse micelles and by addition of DMSO to buffer.

    6. Characterization of the Peroxidase Activity of CYP119, a Thermostable P450 From Sulfolobus acidocaldarius (pages 420–425)

      Kersten S. Rabe, Kathrin Kiko and Christof M. Niemeyer

      Version of Record online: 21 DEC 2007 | DOI: 10.1002/cbic.200700450

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      Wrong extremophile. The thermostable P450 enzyme CYP119, which has potential as a versatile biocatalyst, originates from the thermophilic organism Sulfolobus acidocaldarius, rather than from S. solfataricus as previously assumed. A novel peroxidation reaction of this enzyme was explored, and its biocatalytic activity in the epoxidation of styrene was significantly improved.

    7. Emission under Hypoxia: One-Electron Reduction and Fluorescence Characteristics of an Indolequinone–Coumarin Conjugate (pages 426–432)

      Kazuhito Tanabe, Nao Hirata, Hiroshi Harada, Masahiro Hiraoka and Sei-ichi Nishimoto

      Version of Record online: 25 JAN 2008 | DOI: 10.1002/cbic.200700458

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      Hypoxia-imaging probes: A reactivity characteristic of indolequinone derivatives, substituents of which can be removed by one-electron reduction under anaerobic conditions, was exploited to develop a fluorescent probe for disease-relevant hypoxia. Only under hypoxic conditions does the conjugate IQ-Cou undergo decomposition to release a fluorescent coumarin chromophore upon X irradiation or incubation in the presence of a reduction enzyme (see graph).

    8. The Search for Novel Human Pancreatic α-Amylase Inhibitors: High-Throughput Screening of Terrestrial and Marine Natural Product Extracts (pages 433–438)

      Chris A. Tarling, Kate Woods, Ran Zhang, Harry C. Brastianos, Gary D. Brayer, Raymond J. Andersen and Stephen G. Withers

      Version of Record online: 23 JAN 2008 | DOI: 10.1002/cbic.200700470

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      Nature mining: Most new chemical entities that have been released onto the market recently are based on natural products. The NCI open repository is therefore an ideal library to search for novel inhibitors of human pancreatic α-amylase. Analysis of 30 000 crude biological extracts was undertaken by high-throughput screening (HTS) and montbretin A, a tight-binding highly selective competitive inhibitor, was identified.

    9. An Integrated Device for Monitoring Time-Dependent in vitro Expression From Single Genes in Picolitre Droplets (pages 439–446)

      Fabienne Courtois, Luis F. Olguin, Graeme Whyte, Daniel Bratton, Wilhelm T. S. Huck, Chris Abell and Florian Hollfelder

      Version of Record online: 29 JAN 2008 | DOI: 10.1002/cbic.200700536

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      Monoclonal droplets. An integrated microfluidic device for picolitre droplet formation, incubation and screening of ∼106 experiments has been designed and used for highly efficient in vitro expression of GFP in “monoclonal” droplets. The high efficiency allows protein expression from a single molecule of DNA template, in which genotype and phenotype are combined in one emulsion compartment.

    10. Heterologous Expression And Genetic Engineering of the Phenalinolactone Biosynthetic Gene Cluster by Using Red/ET Recombineering (pages 447–454)

      Tina M. Binz, Silke C. Wenzel, Hans-Jörg Schnell, Andreas Bechthold and Rolf Müller

      Version of Record online: 21 DEC 2007 | DOI: 10.1002/cbic.200700549

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      Mobilizing complex secondary metabolite pathways. By using Red/ET recombineering, the 35 genes of the phenalinolactone biosynthetic pathway were combined into one construct and heterologously expressed in different host strains. After genetic modification of the gene cluster on the expression construct, a new phenalinolatcone derivative was generated.

    11. Biophysical Properties of CDAN/DOPE-Analogue Lipoplexes Account for Enhanced Gene Delivery (pages 455–463)

      Steven Fletcher, Ayesha Ahmad, Wayne S. Price, Michael R. Jorgensen and Andrew D. Miller

      Version of Record online: 8 JAN 2008 | DOI: 10.1002/cbic.200700552

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      Delivering DNA. Cationic liposome-mediated nucleic acid delivery is a prevalent synthetic nonviral vector technology under development for gene therapy, and may become the vector system of choice for many future gene therapy applications if improved in vivo efficacy is achieved. Dialkynoyl DOPE analogues allow for the preparation of transfection-competent, lower charged cationic lipoplexes through elevated Lα/HII phase transition temperatures.

    12. Oligodeoxynucleotides Containing 3-Bromo-3-deazaadenine and 7-Bromo-7-deazaadenine 2′-Deoxynucleosides as Chemical Probes to Investigate DNA–Protein Interactions (pages 464–470)

      Noriaki Minakawa, Yuri Kawano, Shunpei Murata, Naonori Inoue and Akira Matsuda

      Version of Record online: 24 JAN 2008 | DOI: 10.1002/cbic.200700580

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      In the right groove. Brominated oligodeoxynucleotide duplexes make versatile pairs of chemical probes for the investigation of DNA–protein interactions, with NF-κB and RNase H as model proteins. When an ODN containing 7-bromo-7-deaza-2′-deoxyadenosine formed a duplex, the bromo substituent, located in the major groove of the duplex, inhibited interaction with NF-κB. In contrast, a duplex containing 3-bromo-3-deaza-2′-deoxyadenosine, the bromo substituent of which is located in the minor groove, did not interact with RNase H.

  8. Preview

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. Corrigendum
    5. News
    6. Highlight
    7. Communications
    8. Full Papers
    9. Preview
    1. You have free access to this content
      Preview: ChemBioChem 4/2008 (page 474)

      Version of Record online: 8 FEB 2008 | DOI: 10.1002/cbic.200890008

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