ChemBioChem

Cover image for Vol. 9 Issue 9

June 16, 2008

Volume 9, Issue 9

Pages 1329–1514

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. Cover Picture: Rational Design of Highly Active and Selective Ligands for the α5β1 Integrin Receptor (ChemBioChem 9/2008) (page 1329)

      Dominik Heckmann, Axel Meyer, Burkhardt Laufer, Grit Zahn, Roland Stragies and Horst Kessler

      Version of Record online: 9 JUN 2008 | DOI: 10.1002/cbic.200890032

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      The cover picture shows the Conolly surface of the X-ray structure of the integrin αvβ3 and the homology model of the related integrin α5β1. The spatial differences between both integrins have been used to develop biased compound libraries that yield high-affinity ligands which bind to α5β1 in the range of 1 nM but have very low affinity for αvβ3. Both integrins are involved in angiogenesis but their individual role is still under debate. The ligands described here allow us to study the biological roles of both integrins and might additionally serve as potential drug candidates to target selectively the α5β1 integrin in the antiangiogenic therapy of cancer and age-related macular degeneration. For further information, see the article by H. Kessler et al. on p. 1397 ff.

  2. Graphical Abstract

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

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

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. Turning Pages (Nobel Lecture) (pages 1342–1359)

      Oliver Smithies

      Version of Record online: 9 JUN 2008 | DOI: 10.1002/cbic.200800205

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      On target: In 2007, Oliver Smithies was one of the scientists awarded the Nobel Prize for Physiology or Medicine for “their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells”. Here he talks about his work on homologous recombination and gene targeting, as well as giving advice about, among other things, home-made lab apparatus.

  5. Highlight

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. Searching Combinatorial Libraries for Native Proteins with Novel Folds (pages 1361–1363)

      Jennifer L. Watkins and John C. Chaput

      Version of Record online: 7 MAY 2008 | DOI: 10.1002/cbic.200800147

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      Shaping up: Discovering native proteins in large combinatorial libraries is a formidable challenge. Focused libraries composed of randomly distributed secondary structural elements can be used to rapidly identify amino acid sequences that adopt cooperatively folded structures. This approach holds great promise for exploring the diversity of protein shapes available to nature's set of structural elements.

  6. Communications

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. Generation of shRNA Pool Library: A Revision of the Biological Technique from the Viewpoint of Chemistry (pages 1365–1367)

      Demin Zhou, Cuiying Wang, Jing Zhang, Josh Bliesath, Qiuchen S. He, Ning Ke, Dehua Yu, Qixiang Li, Li-He Zhang and Flossie Wong-Staal

      Version of Record online: 24 APR 2008 | DOI: 10.1002/cbic.200800049

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      Unbending the hairpin. A method for the generation of a shRNA pool library, which can be used to perform reverse-genetic screens for genome-wide evaluation of human genes is presented. The thermodynamical issues that limit the previously reported biological technique for shRNA library construction is addressed by converting an intermolecular primer extension into an intramolecular extension.

    2. NMR-Guided Fragment-Based Approach for the Design of AAC(6′)-Ib Ligands (pages 1368–1371)

      Thomas Lombès, Guillaume Bégis, Frédérique Maurice, Serge Turcaud, Thomas Lecourt, Frédéric Dardel and Laurent Micouin

      Version of Record online: 7 MAY 2008 | DOI: 10.1002/cbic.200700677

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      Reverse n.O.e. pumping in the detection and optimisation of ligands: Ligand-observed NMR experiments have been used to drive the detection and optimisation of non-aminoglycosidic ligands for AAC(6′)Ib, one of the most clinically important resistance enzymes to aminoglycosides. This fragment-based approach has been conducted without any need for NMR structural assignment of the target, and has been validated by the preparation of a bisubstrate inhibitor.

    3. The Fluorescent Amino Acid p-Cyanophenylalanine Provides an Intrinsic Probe of Amyloid Formation (pages 1372–1374)

      Peter Marek, Ruchi Gupta and Daniel P. Raleigh

      Version of Record online: 13 MAY 2008 | DOI: 10.1002/cbic.200800052

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      Subtle ways: Analogues of amyloid-forming polypeptides have been developed by using p-cyanophenylalanine as a sensitive, noninvasive, intrinsic probe of amyloid formation. p-Cyanophenylalanine (see figure) is a very conservative substitution for phenylalanine or tyrosine, and its fluorescence is incredibly sensitive to the environment; these facets make it a powerful probe of amyloid formation.

    4. Dehydrophenylalanine (ΔPhe) as a β Breaker: Extended Structure Terminated by a ΔPhe-Induced Turn in the Pentapeptide Boc-Phe1-Ala2-Ile3-ΔPhe4-Ala5-OMe (pages 1375–1378)

      Madhvi Gupta, Rudresh Acharya, Aseem Mishra, Suryanarayanarao Ramakumar, Faizan Ahmed and Virander Singh Chauhan

      Version of Record online: 13 MAY 2008 | DOI: 10.1002/cbic.200800053

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      Breaking the sheets: Crystallography studies illustrated the potential of α,β-dehydrophenylalanine (ΔPhe) to interrupt the propagation of an extended structure in the de novo designed pentapeptide 1. To further explore the role of ΔPhe as a β-breaker residue, it was incorporated into the 16–20 segment of the Aβ1–40 sequence. TEM studies suggest that ΔPhe might be useful as a β breaker in peptide-based antifibrillizing drugs.

    5. Contribution of Fluorophores to Protein Kinase C FRET Probe Performance (pages 1379–1384)

      Christiane A. Jost, Gregor Reither, Carsten Hoffmann and Carsten Schultz

      Version of Record online: 29 APR 2008 | DOI: 10.1002/cbic.200700728

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      Pairing probes: Recently, we prepared several probes that monitor protein kinase C activities in living cells based on a pleckstrin fragment sandwiched between two fluorescent proteins, GFP2 and EYFP. Herein, we replaced the fluorescent proteins (FPs) with monomeric variants which resulted in nonfunctional probes. This suggested that fluorophore dimerization actively participated in probe performance.

    6. The Wall Teichoic Acid Polymerase TagF Efficiently Synthesizes Poly(glycerol phosphate) on the TagB Product Lipid III (pages 1385–1390)

      Mark P. Pereira, Jefferey W. Schertzer, Michael A. D'Elia, Kalinka P. Koteva, Donald W. Hughes, Gerard D. Wright and Eric D. Brown

      Version of Record online: 8 MAY 2008 | DOI: 10.1002/cbic.200800026

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      One piece at a time: Glycerol phosphate polymerization by the TagF enzyme is investigated through the use of a synthetic analogue of a teichoic acid intermediate. Analysis of polymerization products and reaction kinetics of the enzyme suggest a distributive assembly of the teichoic acid polymer on the TagB product lipid III.

    7. Covalent Fluorescence Labeling of His-Tagged Proteins on the Surface of Living Cells (pages 1391–1395)

      Martin Hintersteiner, Thomas Weidemann, Thierry Kimmerlin, Nimet Filiz, Christof Buehler and Manfred Auer

      Version of Record online: 6 MAY 2008 | DOI: 10.1002/cbic.200800089

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      Labeling His-tagged proteins on living cells. NTA-based covalent labeling reagents for His-tagged proteins were designed by combining the oligo-His directing effect of Ni-NTA with the irreversible reaction of a photocrosslinker. Using these new probes, a simple five-minute protocol for labeling His-tagged proteins on living cells was derived.

  7. Full Papers

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
    1. Rational Design of Highly Active and Selective Ligands for the α5β1 Integrin Receptor (pages 1397–1407)

      Dominik Heckmann, Axel Meyer, Burkhardt Laufer, Grit Zahn, Roland Stragies and Horst Kessler

      Version of Record online: 15 MAY 2008 | DOI: 10.1002/cbic.200800045

      Thumbnail image of graphical abstract

      Designer ligands: Based on a homology model of the integrin receptor, ligands have been designed and optimised for high affinity for the α5β1 subtype, and high selectivity against the αvβ3 subtype. The identification of hotspot mutations allowed the synthesis of new α5β1 ligands as well as induction of selectivity for formerly nonspecific ligands. The best compounds of the series displayed an IC50 value in the low nanomolar range and selectivities that exceeded 8000-fold.

    2. The Corrin Moiety of Coenzyme B12 is the Determinant for Switching the btuB Riboswitch of E. coli (pages 1408–1414)

      Sofia Gallo, Michael Oberhuber, Roland K. O. Sigel and Bernhard Kräutler

      Version of Record online: 28 MAY 2008 | DOI: 10.1002/cbic.200800099

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      High binding affinity not needed: We report the investigation of the rearrangement of the three-dimensional structure of the btuB riboswitch upon binding to four different B12 derivatives. Surprisingly, only the central portion of coenzyme B12 (shown in red) is required to switch the B12 riboswitch of E. coli, but not the characteristic “base-on” structure of coenzyme B12, the large apical groups of which merely strengthen binding to the RNA.

    3. Extracellular Synthesis of Crystalline Silver Nanoparticles and Molecular Evidence of Silver Resistance from Morganella sp.: Towards Understanding Biochemical Synthesis Mechanism (pages 1415–1422)

      Rasesh Y. Parikh, Sanjay Singh, B. L. V. Prasad, Milind S. Patole, Murali Sastry and Yogesh S. Shouche

      Version of Record online: 19 MAY 2008 | DOI: 10.1002/cbic.200700592

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      Making the microbes work for us: The synthesis of extracellular crystalline silver nanoparticles from silver-resistant Morganella sp. could provide a cost-effective and ecologically friendly preparative protocol. The best exploration of the bacterium for such activity is only possible if the biochemical mechanism of synthesis is understood. The silverresistance machinery and extracellular proteins that are specifically associated with silver nanoparticles could be targeted for such a purpose.

    4. α-Lactosylceramide as a Novel “Sugar-Capped” CD1d Ligand for Natural Killer T Cells: Biased Cytokine Profile and Therapeutic Activities (pages 1423–1430)

      Wenpeng Zhang, Xincheng Zheng, Chengfeng Xia, Ramu Sridhar Perali, Qingjia Yao, Yang Liu, Pan Zheng and Peng George Wang

      Version of Record online: 13 MAY 2008 | DOI: 10.1002/cbic.200700625

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      A sugar capped CD1d ligand: The compound α-lactosylceramide (α-LacCer) was synthesized and demonstrated to be capable of stimulating invariant natural killer T cells to proliferate and release cytokines, both in vitro and in vivo, with a bias towards T helper 2 cytokines. The processing by β-glycosidase was critical for α-LacCer activity; this shows that the capping sugar plays an important role in α-LacCer's cytokine-releasing profile.

    5. Computer-Based De Novo Design, Synthesis, and Evaluation of Boronic Acid-Based Artificial Receptors for Selective Recognition of Dopamine (pages 1431–1438)

      Shan Jin, Minyong Li, Chunyuan Zhu, ViLinh Tran and Binghe Wang

      Version of Record online: 21 MAY 2008 | DOI: 10.1002/cbic.200700663

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      Boronic identity: A series of boronic acid-based receptors for dopamine were designed and synthesized. All sensors showed preferential recognition of dopamine under near physiological conditions, and displayed selectivity that was up to tenfold higher than that of epinephrine. We propose a three-point binding model (highlighted in the scheme), which was supported by NMR spectroscopy studies.

    6. Theoretical and Experimental Evaluation of a CYP106A2 Low Homology Model and Production of Mutants with Changed Activity and Selectivity of Hydroxylation (pages 1439–1449)

      Michael Lisurek, Birgit Simgen, Iris Antes and Rita Bernhardt

      Version of Record online: 15 MAY 2008 | DOI: 10.1002/cbic.200700670

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      Custom CYPs: A homology model of CYP106A2, a bacterial steroid hydroxylase, has been created and was evaluated thoroughly by using a combination of numerous theoretical structure evaluation tools and mutagenesis data. The docked complex of CYP106A2 with the substrate progesterone was used to predict mutants with substantially changed hydroxylation profiles towards progesterone hydroxylation.

    7. Identification of Bacterial Carotenoid Cleavage Dioxygenase Homologues That Cleave the Interphenyl α,β Double Bond of Stilbene Derivatives via a Monooxygenase Reaction (pages 1450–1461)

      Erinn K. Marasco and Claudia Schmidt-Dannert

      Version of Record online: 13 MAY 2008 | DOI: 10.1002/cbic.200700724

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      Cleavage by oxygen: Bacterial homologues of a new class of nonheme-type oxygenases that were first identified in plants and animals as carotenoid cleavage enzymes have been identified and found not to cleave carotenoids, but instead show activity with stilbenes and farnesol. Oxidative cleavage of the α,β-interphenyl double bond of stilbene occurred via a monooxygenase mechanism.

    8. Synthesis and Transfection Activity of New Cationic Phosphoramidate Lipids: High Efficiency of an Imidazolium Derivative (pages 1462–1471)

      Mathieu Mével, Gilles Breuzard, Jean-Jacques Yaouanc, Jean-Claude Clément, Pierre Lehn, Chantal Pichon, Paul-Alain Jaffrès and Patrick Midoux

      Version of Record online: 2 MAY 2008 | DOI: 10.1002/cbic.200700727

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      A potential new class of cationic lipids for gene transfer: A series of cationic phosphoramidate lipids has been synthesised. The phosphoramidate lipid 1, characterised by a polar head in the form of an imidazolium group, in association with DOPE as co-lipid, formed negative complexes with a plasmid DNA. These complexes displayed high transfection efficiency with low cytotoxicity.

    9. Real-Time Amperometric Analysis of Reactive Oxygen and Nitrogen Species Released by Single Immunostimulated Macrophages (pages 1472–1480)

      Christian Amatore, Stéphane Arbault, Cécile Bouton, Jean-Claude Drapier, Hala Ghandour and Alaric C. W. Koh

      Version of Record online: 19 MAY 2008 | DOI: 10.1002/cbic.200700746

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      What's in a deadly cocktail? Activated macrophages are known to release a complicated mix of reactive oxygen/nitrogen species during phagocytosis. This mixture was analyzed, in real time, by amperometry at platinized carbon electrodes. The main “ingredients” of the cocktail released by IFN-γ/LPS-stimulated RAW 264.7 macrophages were detected as: nitric oxide, peroxynitrite, and nitrite.

    10. Electrochemically Protected Copper(I)-Catalyzed Azide–Alkyne Cycloaddition (pages 1481–1486)

      Vu Hong, Andrew K. Udit, Richard A. Evans and M. G. Finn

      Version of Record online: 26 MAY 2008 | DOI: 10.1002/cbic.200700768

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      Convenient regeneration: The title “click” reaction is enabled by the presence of a reducing electrochemical potential and accelerating Cu-binding ligands to provide a convenient method for synthetic and bioconjugation ligations by using a highly active, but air-sensitive, catalyst.

    11. Arginine Dynamics in a Membrane-Bound Cationic Beta-Hairpin Peptide from Solid-State NMR (pages 1487–1492)

      Ming Tang, Alan J. Waring and Mei Hong

      Version of Record online: 29 APR 2008 | DOI: 10.1002/cbic.200800005

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      Dynamics and structure. The motion of the Arg residues in the antimicrobial peptide PG-1 was studied by using magic-angle spinning NMR spectroscopy. The dipolar couplings and chemical shift anisotropies of two Arg residues are averaged by motion to different extents. The β-turn Arg11 has larger motional amplitudes than the β-strand Arg4; this is consistent with the oligomeric structure and lipid interaction of this peptide in the membrane.

    12. Ionic Liquids and Proteases: A Clean Alliance for Semisynthesis (pages 1493–1499)

      Nicole Wehofsky, Christian Wespe, Vaclav Cerovsky, Andreas Pech, Eva Hoess, Rainer Rudolph and Frank Bordusa

      Version of Record online: 28 MAY 2008 | DOI: 10.1002/cbic.200800025

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      The trick is the solvent: Ionic liquids of the type 1,3-dimethyl-imidazolium dimethylphosphate ([MMIM][Me2PO4]) were used as promising additives to promote the irreversible reverse proteolysis of low-water-soluble peptide fragments without competing peptide bond cleavages.

    13. In vivo Mutational Analysis of the Mupirocin Gene Cluster Reveals Labile Points in the Biosynthetic Pathway: the “Leaky Hosepipe” Mechanism (pages 1500–1508)

      Ji'en Wu, Joanne Hothersall, Carlo Mazzetti, Yvonne O'Connell, Jennifer A. Shields, Ayesha S. Rahman, Russell J. Cox, John Crosby, Thomas J. Simpson, Christopher M. Thomas and Christine L. Willis

      Version of Record online: 8 MAY 2008 | DOI: 10.1002/cbic.200800085

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      Metabolic leaks: Blocks in the modular polyketide synthase assembly line induced by mutation of components of the HMG CoA analogue (mupH) containing gene cassette and other tailoring genes result in a common phenotype in which both mupirocin H and the novel metabolite mupiric acid are produced. This has important implications for understanding the dynamics of intermediate flow and interpretation of mutational analysis experiments in the generic AT-less polyketide family of metabolites.

  8. Book Reviews

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

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Review
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Reviews
    10. Preview
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      Preview: ChemBioChem 10/2008 (page 1514)

      Version of Record online: 9 JUN 2008 | DOI: 10.1002/cbic.200890035

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