ChemBioChem

Cover image for Vol. 9 Issue 10

July 2, 2008

Volume 9, Issue 10

Pages 1517–1674

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
    8. Book Review
    9. Preview
    1. Cover Picture: Calix[n]arene-Based Glycoclusters: Bioactivity of Thiourea-Linked Galactose/Lactose Moieties as Inhibitors of Binding of Medically Relevant Lectins to a Glycoprotein and Cell-Surface Glycoconjugates and Selectivity among Human Adhesion/Growth-Regulatory Galectins (ChemBioChem 10/2008) (page 1517)

      Sabine André, Francesco Sansone, Herbert Kaltner, Alessandro Casnati, Jürgen Kopitz, Hans-Joachim Gabius and Rocco Ungaro

      Article first published online: 23 JUN 2008 | DOI: 10.1002/cbic.200890036

      Thumbnail image of graphical abstract

      The cover picture shows how distinct glycoclusters can interfere with the activity of human adhesion/growth-regulatory proteins. The three human lectins of medical relevance (Gal-1, Gal-3 and Gal-4) selectively bind to multivalent calixarene glycoconjugates, neutralizing lectin activity. Of note is that the sugar ligands are presented with different spatial topology. This diversity is depicted as generated from an ancient Calix, the etymological origin of the name of these macrocycles. The orange ellipses on the cell surface and on the macrocycle scaffolds (in blue) represent sugar units that compete for lectin binding. In vitro bioassays indicate clear intergalectin selectivity of inhibition that depends on the conformational properties of the calix[n]arene scaffold and on the valency of the glycoclusters. The assays also reveal the potent reactivity of the glycoclusters towards a plant toxin from Viscum album L., akin to ricin. Further details can be found in the article by H.-J. Gabius, R. Ungaro, et al. on p. 1649 ff.

  2. Graphical Abstract

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
    8. Book Review
    9. Preview
    1. Graphical Abstract: ChemBioChem 10/2008 (pages 1519–1525)

      Article first published online: 23 JUN 2008 | DOI: 10.1002/cbic.200890037

  3. News

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

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
    8. Book Review
    9. Preview
    1. The Making of a Scientist II (Nobel Lecture) (pages 1530–1543)

      Mario R. Capecchi

      Article first published online: 13 JUN 2008 | DOI: 10.1002/cbic.200800239

      Perturbing genes: The incorporation of >100 HSV-tk plasmid molecules into a single, ordered, concatemer when injected into somatic cells was the first demonstration of homologous recombination between cointroduced DNA molecules in cultured mammalian cells. From this came first the idea that manipulating this efficient machinery would allow any endogenous cellular gene in cultured cells to be mutated in any chosen way, and, eventually, the award of the 2007 Nobel Prize for Physiology or Medicine.

  5. Communications

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
    8. Book Review
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    1. Heparin Dependent Coiled-Coil Formation (pages 1545–1548)

      Mark Nitz, Anthony Rullo and Matias Xiao Yue Ding

      Article first published online: 28 MAY 2008 | DOI: 10.1002/cbic.200800056

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      Coiled-coil complexes: Heparin binding to designed peptides mediates the formation of a defined coil–coil complex through a polyelectrolyte interaction. The interaction occurs at physiological ionic strengths and is coupled to a ratiometric change in fluorescence. The interaction is specific to heparin over other common biological polyanions such as DNA, chondroitin sulfate A, or polyglutamic acid.

    2. Two Functionally Redundant Sfp-Type 4′-Phosphopantetheinyl Transferases Differentially Activate Biosynthetic Pathways in Myxococcus xanthus (pages 1549–1553)

      Peter Meiser and Rolf Müller

      Article first published online: 28 MAY 2008 | DOI: 10.1002/cbic.200800077

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      A liberal alliance. Two Sfp-type 4′-phosphopantetheinyl transferases (PPTases, MxPpt1 and MxPpt2) are encoded in the Myxococcus xanthus DK1622 genome. Disruption or over-expression led to significant changes in secondary metabolism, but production of known compounds was not abolished. Both PPTases thus apparently differ in their specificity for biosynthetic pathways by employing carrier proteins from polyketide synthases and nonribosomal peptide synthetases.

    3. Glycosylation of Acyclic and Cyclic Aglycone Substrates by Macrolide Glycosyltransferase DesVII/DesVIII: Analysis and Implications (pages 1554–1558)

      Svetlana A. Borisova, Hak Joong Kim, Xiaotao Pu and Hung-wen Liu

      Article first published online: 11 JUN 2008 | DOI: 10.1002/cbic.200800155

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      Studies of the macrolide glycosyltransferase, DesVII/DesVIII, showed that when multiple hydroxyl groups are present, no regiospecificity of glycosylation is observed for the linear substrates. In contrast, when cyclic substrates with multiple glycosylation sites were tested, it displayed excellent regiospecificity in most cases. These results clearly indicate that this enzyme pair is a valuable tool for glycodiversification.

    4. Acyl-Carrier Protein–Phosphopantetheinyltransferase Partnerships in Fungal Fatty Acid Synthases (pages 1559–1563)

      Jason M. Crawford, Anna L. Vagstad, Kenneth C. Ehrlich, Daniel W. Udwary  and Craig A. Townsend

      Article first published online: 12 JUN 2008 | DOI: 10.1002/cbic.200700659

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      Fungal fatty acids: The synthesis of fatty acids is an essential primary metabolic process for energy storage and cellular structural integrity. Fungal fatty acid synthases (FASs) are unusual among FASs and self-pantetheinylate to their active holo-form. Dissection of the FAS α-subunit involved in aflatoxin biosynthesis and in vitro assays with purified proteins revealed the activation partnerships in the aflatoxin biosynthetic pathway.

    5. Isomerization of the Asp7 Residue Results in Zinc-Induced Oligomerization of Alzheimer’s Disease Amyloid β(1–16) Peptide (pages 1564–1567)

      Philipp O. Tsvetkov, Igor A. Popov, Eugene N. Nikolaev, Alexander I. Archakov, Alexander A. Makarov and Sergey A. Kozin

      Article first published online: 28 MAY 2008 | DOI: 10.1002/cbic.200700784

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      One small change: Isomerization of Asp7, the most abundant naturally occurring post-translational modification in Alzheimer's disease (AD) amyloid-β peptide (Aβ), causes zinc-induced oligomerization of the Aβ zinc-binding domain and could play a triggering role in pathology onset. Substitution of Asp7 by Asn in Aβ (the Tottori–Japan mutation) might also be significant, since asparagine is known to be much more susceptible than aspartate to spontaneous conversion into isoaspartate.

    6. A Versatile Gold Surface Approach for Fabrication and Interrogation of Glycoarrays (pages 1568–1575)

      Zheng-Liang Zhi, Nicolas Laurent, Andrew K. Powell, Rositsa Karamanska , Margherita Fais , Josef Voglmeir, Adam Wright, Jonathan M. Blackburn, Paul R. Crocker, David A. Russell, Sabine Flitsch, Rob A. Field  and Jeremy E. Turnbull

      Article first published online: 18 JUN 2008 | DOI: 10.1002/cbic.200700788

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      Glycoarrays on gold: A designer gold surface incorporating a self-assembled monolayer with weak protein absorption properties has been optimised for rapid display and interrogation of both native and derivatised glycans in array formats. This rapid, facile approach has diverse applications in glycomics, through exploitation of fluorescence, SPR and MALDI-ToF MS detection methods.

    7. Tetrameric β3-Peptide Bundles (pages 1576–1578)

      Jessica L. Goodman, Matthew A. Molski, Jade Qiu and Alanna Schepartz

      Article first published online: 5 JUN 2008 | DOI: 10.1002/cbic.200800039

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      A question of identity: There is significant interest in the design of discrete, nonproteinaceous quaternary structures. We recently described a series of β3-peptides that assemble into stable octameric bundles. Here we show that bundle stoichiometry is controlled by the bundle core side-chain identity, whereby mutation of leucine to valine supports formation of discrete and stable tetrameric bundles.

    8. Copper Resistance in E. coli: The Multicopper Oxidase PcoA Catalyzes Oxidation of Copper(I) in CuICuII-PcoC (pages 1579–1582)

      Karrera Y. Djoko, Zhiguang Xiao and Anthony G. Wedd

      Article first published online: 6 JUN 2008 | DOI: 10.1002/cbic.200800100

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      Copper export: PcoA and PcoC are soluble proteins expressed to the periplasm as part of the copper-resistance response of E. coli. PcoC binds both CuI and CuII to form air-stable CuICuII-PcoC. The blue multicopper oxidase PcoA has been shown to catalyze oxidation of CuI bound in CuICuII-PcoC to less toxic CuII, which is released into solution. These two proteins may interact with the outer membrane protein PcoB to export excess copper from the periplasm.

    9. A Caged Phosphopeptide-Based Approach for Photochemical Activation of Kinases in Living Cells (pages 1583–1586)

      Takashi Kawakami, Huan Cheng, Shuhei Hashiro, Yasushi Nomura, Shinya Tsukiji, Toshiaki Furuta and Teruyuki Nagamune

      Article first published online: 15 MAY 2008 | DOI: 10.1002/cbic.200800116

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      Kinase photoactivation: We have demonstrated that a caged analogue of SH2 domain-binding phosphotyrosine peptide can be used as a tool for activating an intracellular phosphatidylinositol 3-kinase (PI3K) by light. This approach should be generally applicable to other protein/lipid kinases of which the catalytic activity is regulated by modular phosphopeptide-binding domains.

    10. A Chemical Library Approach to Organic-Modified Peptide Ligands for PDZ Domain Proteins: A Synthetic, Thermodynamic and Structural Investigation (pages 1587–1589)

      D. Gomika Udugamasooriya, Sudhir C. Sharma and Mark R. Spaller

      Article first published online: 28 MAY 2008 | DOI: 10.1002/cbic.200800126

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      Unnatural attachments: While a variety of native peptides can bind PDZ domains, there is a pressing need for small ligands with enhanced affinity, selectivity, and stability to support biological inquiry into this family of signaling proteins. A method, transferable to PDZ domains as a class, has been developed in which a lead peptide template is rapidly modified by nonpeptidic organic acids in a library format to give binding agents of higher affinity.

  6. Full Papers

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
    8. Book Review
    9. Preview
    1. Structural, Functional and Calorimetric Investigation of MosA, a Dihydrodipicolinate Synthase from Sinorhizobium meliloti L5–30, does not Support Involvement in Rhizopine Biosynthesis (pages 1591–1602)

      Christopher P. Phenix, Kurt Nienaber, Pui Hang Tam, Louis T. J. Delbaere and David R. J. Palmer 

      Article first published online: 6 JUN 2008 | DOI: 10.1002/cbic.200700569

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      To be or not to be: MosA is a protein that has been reported to be a dihydrodipicolinate synthase and a methyltransferase. We have solved the crystal structure to 1.95 Å resolution and investigated both functions by HPLC and isothermal titration microcalorimetry. We have measured the thermodynamics of covalent binding of MosA to pyruvate and the competitive inhibitor 2-oxobutyrate. We find no evidence of methyltransferase activity.

    2. Reassembly of Anthramycin Biosynthetic Gene Cluster by Using Recombinogenic Cassettes (pages 1603–1608)

      Yunfeng Hu, Vanessa V. Phelan, Chris M. Farnet, Emmanuel Zazopoulos and Brian O. Bachmann

      Article first published online: 2 JUN 2008 | DOI: 10.1002/cbic.200800029

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      Cosmid mating: We describe a new general technique that can be used to reconstruct large biosynthetic pathways from overlapping cosmids by retrofitting each cosmid with a “recombinogenic cassette” that contains a shared homologous element and orthogonal antibiotic markers. Without enzymatic ligation or PCR of cosmid DNA, the anthramycin gene cluster from Streptomyces refuineus was recapitulated and heterologously expressed in Streptomyces lividans.

    3. Generation of Novel Pikromycin Antibiotic Products Through Mutasynthesis (pages 1609–1616)

      Shuchi Gupta, Venkatraman Lakshmanan, Beom Seok Kim, Robert Fecik and Kevin A. Reynolds

      Article first published online: 2 JUN 2008 | DOI: 10.1002/cbic.200700635

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      Mutasynthesis in pikromycin PKS: The amenability of pikromycin polyketide synthase to mutational biosynthesis has been demonstrated. A natural triketide and its analogues, activated as N-acetylcysteamine thioesters, were synthesized and fed to a pikAI-deleted strain; this led to the production of new antibiotics. A vinyl analogue was found to have better antibacterial activity than pikromycin.

    4. Synthesis of a Stabilized Version of the Imidazolone DNA Lesion (pages 1617–1622)

      Heiko Mueller, Mathias Hopfinger and Thomas Carell

      Article first published online: 28 MAY 2008 | DOI: 10.1002/cbic.200700690

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      Stabilized DNA lesions: Oxidation processes induce the formation of more than 50 known DNA lesions. We report herein, the synthesis of a stabilized version of the highly mutagenic imidazolone DNA lesion. The ability to prepare the cdIz lesion analogue in DNA is a major step forward because it allows cocrystallization studies of cdIz-containing DNA with wild-type repair enzymes such as FPG/MutM.

    5. Selenoglutaredoxin as a Glutathione Peroxidase Mimic (pages 1623–1631)

      Giulio Casi, Gerard Roelfes and Donald Hilvert

      Article first published online: 11 JUN 2008 | DOI: 10.1002/cbic.200700745

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      Total synthesis and characterization of selenoglutaredoxin: A glutaredoxin variant that contains an active-site selenocysteine was prepared by native chemical ligation. The artificial selenoenzyme is a surprisingly poor peroxidase, but it efficiently catalyzes the reduction of mixed glutathionyl disulfides.

    6. A β-1,4-Galactosyltransferase from Helicobacter pylori is an Efficient and Versatile Biocatalyst Displaying a Novel Activity for Thioglycoside Synthesis (pages 1632–1640)

      Darius-Jean Namdjou, Hong-Ming Chen, Evguenii Vinogradov, Denis Brochu, Stephen G. Withers and Warren W. Wakarchuk

      Article first published online: 19 MAY 2008 | DOI: 10.1002/cbic.200700775

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      Widening the scope of biocatalysis: The galactosyltransferase from Helicobacter pylori (HP0826) offers two novel synthetic enzymatic reactions. The thiodisaccharide Gal-β-S-1,4-GlcNAc-pNP [3; as formed from UDP-Galactose (1) and pNP-4S-β-GlcNAc (2)] and the Leishmaniasis-associated structure Gal-β-1,4-Man-pNP were prepared in quantitative yield and characterized by MS and NMR. Possible applications of both compounds are described.

    7. Thermodynamic Analysis of Nylon Nucleic Acids (pages 1641–1648)

      Yu Liu, Risheng Wang, Liang Ding, Ruojie Sha, Philip S. Lukeman, James W. Canary and Nadrian C. Seeman

      Article first published online: 9 JUN 2008 | DOI: 10.1002/cbic.200800032

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      Out of the closet: Oligonucleotides containing nylon nucleic acids were studied and were found to form stable complexes with complementary DNA and RNA. They showed significantly enhanced binding affinity when compared with nonamide-linked precursor strands (see figure). CD spectroscopy studies suggest that stabilization of the duplexes in this system originates from conformational restriction enforced by the amide links.

    8. Calix[n]arene-Based Glycoclusters: Bioactivity of Thiourea-Linked Galactose/Lactose Moieties as Inhibitors of Binding of Medically Relevant Lectins to a Glycoprotein and Cell-Surface Glycoconjugates and Selectivity among Human Adhesion/Growth-Regulatory Galectins (pages 1649–1661)

      Sabine André, Francesco Sansone, Herbert Kaltner, Alessandro Casnati, Jürgen Kopitz, Hans-Joachim Gabius and Rocco Ungaro

      Article first published online: 28 MAY 2008 | DOI: 10.1002/cbic.200800035

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      Glycocalixarenes hit on lectins with medical relevance: A set of 14 calix[n]arenes adorned with variable numbers of galactose or lactose units has been synthesized, and their interactions with lectins of clinical interest (either biohazard or factor in tumor progression) were studied. A preference for lactose over galactose epitopes, glycoside cluster effects, and a dependence of selective lectin inhibition on shape and valency of the glycoclusters are revealed.

    9. Layer-By-Layer Assembly of Viral Nanoparticles and Polyelectrolytes: The Film Architecture is Different for Spheres Versus Rods (pages 1662–1670)

      Nicole F. Steinmetz, Kim C. Findlay, Timothy R. Noel, Roger Parker, George P. Lomonossoff and David J. Evans

      Article first published online: 6 JUN 2008 | DOI: 10.1002/cbic.200800070

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      Taking shape: The assembly mechanisms of spherical versus rod-shaped viral nanoparticles and polyelectrolytes have been studied. We found that the topologies of the self-assembled architectures are markedly influenced by particle shape. Sphere-like particles were incorporated into an alternating array, as illustrated on the left side of the figure. In contrast, rods were found to be excluded and floated on top of the structure (right-hand side).

  7. Book Review

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

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
    8. Book Review
    9. Preview
    1. Preview: ChemBioChem 11/2008 (page 1674)

      Article first published online: 23 JUN 2008 | DOI: 10.1002/cbic.200890039

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