ChemBioChem

Cover image for ChemBioChem

April 4, 2003

Volume 4, Issue 4

Pages 241–354

    1. Cover Picture: A Powerful Combinatorial Screen to Identify High-Affinity Terbium(III)-Binding Peptides (ChemBioChem 4/2003) (page 241)

      Mark Nitz, Katherine J. Franz, Rebecca L. Maglathlin and Barbara Imperiali

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390042

    2. Graphical Abstract: ChemBioChem 4/2003 (pages 243–247)

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390043

    3. Biogenic Silica Patterning: Simple Chemistry or Subtle Biology? (pages 251–259)

      Thibaud Coradin and Pascal Jean Lopez

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390044

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      Silica chemistry in the living world. Some microorganisms, such as diatoms (see figure), have learned to build up finely patterned mineral structures by using the many possibilities of silica chemistry and adapting themselves to its constraints. Association of biomimetic chemical approaches with molecular biology techniques should lead to a better understanding of the strategies used by natural systems and should thus provide novel guidelines for material design.

    4. Chemical Chaperones—A New Concept in Drug Research (pages 260–264)

      Thomas Kolter and Michaela Wendeler

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390045

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      A stabilizing influence:D-Galactose and the nojirimycin derivatives 1 and 2 have been successfully applied as “chemical chaperones” in therapy models of Fabry's disease and Gaucher's disease, respectively. These compounds illustrate the concept of specific low-molecular-weight chemical chaperones for the treatment of metabolic disorders.

    5. Lanthanide-Binding Tags as Versatile Protein Coexpression Probes (pages 265–271)

      Katherine J. Franz, Mark Nitz and Barbara Imperiali

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390046

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      Terrific tags: An integrated approach involving combinatorial synthesis, screening, and peptide design has provided peptide sequences of fewer than 20 amino acids that are optimized as high-affinity lanthanide-binding tags (see figure). These tags provide an alternative approach for generating genetically encoded, luminescent protein fusion partners of minimal dimension and versatile application.

    6. A Powerful Combinatorial Screen to Identify High-Affinity Terbium(III)-Binding Peptides (pages 272–276)

      Mark Nitz, Katherine J. Franz, Rebecca L. Maglathlin and Barbara Imperiali

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390047

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      Searching for sequences: Novel lanthanide-binding tags (LBTs) were readily identified as they diffused away from a solid support into an agarose matrix (seen as a luminescent halo surrounding the bead in the figure). Screens of focused libraries led to the identification of peptides with low-nanomolar affinity for Tb3+ ions. Such high affinities greatly reduce the problem of nonspecific lanthanide binding, which should make the peptide sequences identified by this efficient new screening methodology exceptionally useful for further development for biotechnological applications.

    7. On the Generation of Catalytic Antibodies by Transition State Analogues (pages 277–285)

      Montserrat Barbany, Hugo Gutiérrez-de-Terán, Ferran Sanz, Jordi Villà-Freixa and Arieh Warshel

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390048

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      Analyzing analogues: The picture shows Langevin dipoles oriented towards the charge distribution of the transition state (TS) for the Claisen rearrangement from chorismate to prephenate. This prototypical reaction is used to discuss the ability of TS analogues to mimic TSs in order to elicit catalytic antibodies.

    8. Nuclear Localisation Sequence Templated Nonviral Gene Delivery Vectors: Investigation of Intracellular Trafficking Events of LMD and LD Vector Systems (pages 286–298)

      Michael Keller, Richard P. Harbottle, Eric Perouzel, Morvane Colin, Imran Shah, Ahad Rahim, Laurence Vaysse, Anna Bergau, Sylviane Moritz, Christiane Brahimi-Horn, Charles Coutelle and Andrew D. Miller

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390049

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      Shut out by a wall: Transport of exogenous DNA into the nucleus is a prerequisite for successful gene therapy. In vitro, one of the major barriers turns out to be the nuclear membrane, which effectively shields the nucleus from the uptake of exogenous plasmid DNA, as depicted in the figure. The electrostatic complexation of DNA with mu peptide, which harbours a nuclear localisation sequence, is not sufficient to overcome the nuclear barrier. Therefore, for successful gene therapy protocols, strategies must be found to actively promote the uptake of transgenes into the nucleus.

    9. Direct Observations of the Cleavage Reaction of an L-DPPC Monolayer Catalyzed by Phospholipase A2 and Inhibited by an Indole Inhibitor at the Air/Water Interface (pages 299–305)

      Xiuhong Zhai, Junbai Li, Gerald Brezesinski, Qiang He, Helmuth Möhwald, Luhua Lai, Ying Liu, Liang Liu and Ying Gao

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390050

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      Seeing how things shape up: The dynamic progress of the enzymatic hydrolysis reaction of an L-dipalmitoylphosphatidylcholine (L-DPPC) monolayer catalyzed by phospholipase A2 was observed with Brewster angle microscopy. Addition of an indole derivative inhibitor postponed the formation of “C-” or “O-type” domains (see figure) and correspondingly delayed the cleavage of L-DPPC.

    10. Noncovalent Binding of a Reaction Intermediate by a Designed Helix-Loop-Helix Motif—Implications for Catalyst Design (pages 306–318)

      Malin Allert and Lars Baltzer

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390051

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      Matchmaking: A de novo designed folded polypeptide catalyses the transamination of L-Asp to form oxaloacetate in a reactive site tailored to bind the aldimine intermediate (see structure) within bond-forming distance of catalytically active His residues. Peptide sequences that fold into helix-loop-helix motifs were designed to interact with the intermediate through mainly noncovalent charge–charge interactions. The well-defined catalytic sites provided by two of these peptides represent an important advance in de novo catalyst design.

    11. Synthesis of Novel Acceptor Substrates for the Dolichyl Phosphate Mannose Synthase from Yeast (pages 319–332)

      Ines Sprung, Laurence Carmès, Gregory M. Watt and Sabine L. Flitsch

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390052

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      How tolerant is a synthase? A number of bifunctional analogues of dolichyl phosphate were synthesised and found to be accepted as substrates for the dolichyl phosphate mannose synthase (see scheme; GDP=guanosine diphosphate). The attachment of substrates onto solid phase enabled enzymatic mannosylation on solid support.

    12. Redox Potentials of Methanophenazine and CoB-S-S-CoM, Factors Involved in Electron Transport in Methanogenic Archaea (pages 333–335)

      Mario Tietze, Anja Beuchle, Iris Lamla, Nadine Orth, Michael Dehler, Gerhard Greiner and Uwe Beifuss

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390053

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      Potentially important: The redox potentials of methanophenazine and CoB-S-S-CoM (see scheme), two cofactors from methanogenic archaea, strongly support the view that methanophenazine plays a central role in the electron transport system of methane-producing archaea. These redox potentials were measured with a hanging mercury drop electrode as the working electrode and were compared to those of several phenazine ethers.

    13. Developing a Strategy for Activity-Based Detection of Enzymes in a Protein Microarray (pages 336–339)

      Grace Y. J. Chen, Mahesh Uttamchandani, Qing Zhu, Gang Wang and Shao Q. Yao

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390054

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      Spot search: We have developed a microarray-based strategy for detection of three major classes of proteins on the basis of their enzymatic activities (see figure). This is the first protein array technology that allows detection of proteins not merely by their binding, but rather by their enzymatic activities. This strategy, together with increasing efforts in the field of protein-based microarrays, should provide a valuable tool for screening and identification of new enzymes and their potential inhibitors in a high-throughput fashion.

    14. Patterns of DNA-Labeled and scFv-Antibody-Carrying Lipid Vesicles Directed by Material-Specific Immobilization of DNA and Supported Lipid Bilayer Formation on an Au/SiO2 Template (pages 339–343)

      Sofia Svedhem, Indriati Pfeiffer, Charlotte Larsson, Christer Wingren, Carl Borrebaeck and Fredrik Höök

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390055

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      Spots before the eyes: A material-specific surface modification protocol was developed to allow surface-directed immobilization of DNA-labeled lipid vesicles. The potential of similarly immobilized vesicles to act as carriers for water-soluble or transmembrane proteins in, for example, protein-chip applications was demonstrated. The picture shows how fluorescent vesicles labeled with different DNA strands have been directed to one of two complementary-DNA-modified Au spots surrounded by an inert supported lipid bilayer on SiO2.

    15. Book Review: Transcription Regulation in Prokaryotes. By Rolf Wagner (page 351)

      Gerhard Mittler and Michael Meisterernst

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390059

    16. Preview: ChemBioChem 4/2003 (page 354)

      Article first published online: 26 MAR 2003 | DOI: 10.1002/cbic.200390061

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