Cover image for ChemBioChem

December 5, 2003

Volume 4, Issue 12

Pages 1257–1360

    1. Cover Picture: DNA Mismatch-Specific Base Flipping by a Bisacridine Macrocycle (ChemBioChem 12/2003) (page 1257)

      Arnaud David, Nathalie Bleimling, Christine Beuck, Jean-Marie Lehn, Elmar Weinhold and Marie-Paule Teulade-Fichou

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200390121

      The cover picture shows how the conformational equilibrium of a nucleobase in DNA can be changed from the predominant intrahelical position to the extrahelical position (center). This process of base (nucleotide) flipping is achieved naturally by DNA glycosylases and DNA methyltransferases like M.TaqI, which binds the target base in its extrahelical conformation and fills the resulting hole in the DNA (left). Base flipping can also be induced by a small synthetic bisacridine macrocycle that specifically inserts at thermodynamically weakened sites (e.g. base mismatches) in DNA and hence stabilizes the extrahelical conformation of a nucleobase (right). Further details on binding of the bisacridine macrocycle to DNA can be found in the article by E. Weinhold, M.-P. Teulade-Fichou et al. on p. 1326 ff.

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      On Secondary Structure Rearrangements and Equilibria of Small RNAs (page 1263)

      Ronald Micura and Claudia Höbartner

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200390123

    3. Prion Diseases: From Molecular Biology to Intervention Strategies (pages 1268–1284)

      Max Nunziante, Sabine Gilch and Hermann M. Schätzl

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300704

      Of people, prions, and possibilities: Prion diseases are fatal neurodegenerative infectious disorders for which no therapeutic or prophylactic regimens exist. Understanding the molecular biology behind the formation of the pathological isoform of the prion protein is necessary to devise effective antiprion strategies. A variety of chemical antiprion substances have been reported and new findings in the fields of peripheral prion pathogenesis and immune system involvement have fuelled the search for antiprion strategies formerly considered to be entirely impossible. Therapeutic or prophylactic intervention in human prion diseases now seems to be a realistic goal.

    4. Structural Aspects of Adhesion to and Invasion of Host Cells by the Human Pathogen Listeria monocytogenes (pages 1285–1291)

      Wolf-Dieter Schubert and Dirk W. Heinz

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300624

      Thumbnail image of graphical abstract

      Molecular Infection.Listeria monocytogenes, a widespread contaminant of processed food, infects both humans and other mammals by the oral route. The first dedicated step of the infection process is the recognition of human E-cadherin (purple) by the listerial protein internalin (InlA, yellow-green). The bacterium thereby adheres to the epithelial lining of the intestine. It then induces its own uptake into the host cells, where it finds ideal conditions to multiply and spread to neighboring cells. The affinity of InlA for E-cadherin, controlled by Ca2+ (orange sphere), is fine-tuned to allow complex formation in the intestinal lumen and dissociation when uptake has occurred to release the bacterium into the epithelial cell.

    5. Looking at Molecules—An Essay on Art and Science (pages 1293–1297)

      David S. Goodsell

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300747

      Thumbnail image of graphical abstract

      Picture this: Molecular imagery plays an indispensable role in the study of biomolecular structure and function, and the dissemination of these results to colleagues, educators, and the general public. An interdisciplinary combination of structural science, computer graphics, art, and illustration has provided a diverse collection of methods that may be used to explore and present biomolecular subjects, such as the impression of the DNA inside an E. coli cell shown here. Some highlights of the current field of molecular graphics are presented in this essay.

    6. A “Holey” Supramolecular Approach to the Detection of Enzyme Activity (pages 1299–1302)

      Philip A. Gale

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300716

      Thumbnail image of graphical abstract

      Roll out the barrel: Transmembrane channels can be made to act as a component of a sensor if control of transport across a membrane can be linked to a separate chemical process occurring in the system. A new high-throughput fluorometric method for monitoring enzyme activity that employs selective blocking (see figure) and unblocking of synthetic peptidic channels has been developed. The channels consist of β-barrels constructed from a rigid octiphenyl stave to which short peptide chains are attached. By changing their amino acid residues, it is possible to tune the barrel's solubility and transport ability.

    7. Sticky Proteins for Stem Cells (pages 1303–1305)

      Thomas Kolter

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300733

      Thumbnail image of graphical abstract

      Growing the next generation: Functionally active Wnt proteins are palmitoylated (see scheme). This posttranslational modification explains the ability of Wnt proteins to associate tightly with membranes and is required for the induction of self-renewal and proliferation of haematopoietic stem cells.

    8. Chemoenzymatic Synthesis of Branched Oligo- and Polysaccharides as Potential Substrates for Starch Active Enzymes (pages 1307–1311)

      Lionel Greffe, Morten T. Jensen, Claude Bosso, Birte Svensson and Hugues Driguez

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300692

      Thumbnail image of graphical abstract

      Branching out: Branched oligo- and polysaccharides with the amylopectin structure were obtained by an efficient chemoenzymatic synthesis involving CGTase-catalysed condensations of 4II-O-THP-maltosyl fluoride onto panose or pullulan (see scheme; THP tetrahydropyranyl). The two compounds produced are substrates for barley limit dextrinase.

    9. Intracellular Delivery of Bioactive Peptides to RBL-2H3 Cells Induces β-Hexosaminidase Secretion and Phospholipase D Activation (pages 1312–1316)

      John Howl, Sarah Jones and Michelle Farquhar

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300694

      Molecular probes of secretion: Transportan-10 (TP-10), a chimeric cell-penetrating peptide, can effectively deliver peptide cargoes to the intracellular compartment of eukaryotic cells. By using the TP-10 system as an inert vector, a range of mimetic peptides were translocated into RBL-2H3 mast cells. Peptides derived from protein kinase C and the CB1 cannabinoid receptor increased both the secretion of β-hexosaminidase and activated phospholipase D; this indicates that they interact with proteins that regulate signal transduction and membrane fusion.

    10. Adhesion Inhibition of F1C-Fimbriated Escherichia coli and Pseudomonas aeruginosa PAK and PAO by Multivalent Carbohydrate Ligands (pages 1317–1325)

      Reshma Autar, A. Salam Khan, Matthias Schad, Jörg Hacker, Rob M. J. Liskamp and Roland J. Pieters

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300719

      Thumbnail image of graphical abstract

      Alternatives to antibiotics are needed in the battle against resistant bacterial pathogens. One possible alternative, the antiadhesion approach, has been investigated by using mono- and multivalent carbohydrates, such as the one shown here, that were used against Pseudomonas aeruginosa and uropathogenic Escherichia coli.

    11. DNA Mismatch-Specific Base Flipping by a Bisacridine Macrocycle (pages 1326–1331)

      Arnaud David, Nathalie Bleimling, Christine Beuck, Jean-Marie Lehn, Elmar Weinhold and Marie-Paule Teulade-Fichou

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300693

      Thumbnail image of graphical abstract

      A synthetic base flipper: The macrocylic bisacridine BisA (blue) specifically inserts itself into DNA at the site of mismatched base pairs (red) and it is likely to flip one of them out from the DNA helix. This behavior is reminiscent of DNA glycosylases, which recognize lesions in DNA and stabilize the extrahelical conformation of a base for glycosidic bond cleavage. BisA could be used on the one hand as DNA-glycosylase inhibitor and on the other to detect base mismatches in DNA.

    12. Functionalizing Nanocrystalline Metal Oxide Electrodes With Robust Synthetic Redox Proteins (pages 1332–1339)

      Emmanuel Topoglidis, Bohdana M. Discher, Christopher C. Moser, P. Leslie Dutton and James R. Durrant

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300707

      Thumbnail image of graphical abstract

      Caught in the spotlight of a spectrometer, a synthetic cytochrome b protein maquette immobilized on a nanocrystalline SnO2 film with a protein loading of 8 nmol cm−2 was closely examined. A combination of spectroscopic, electrochemical, and ligand binding studies showed that the cyt b/SnO2 electrodes (see figure) exhibit a wide range of functionality, including reversible heme electrochemistry and photochemistry, and carbon monoxide binding.

    13. Metal-Chelating Amino Acids As Building Blocks For Synthetic Receptors Sensing Metal Ions And Histidine-Tagged Proteins (pages 1340–1344)

      Silke Hutschenreiter, Lars Neumann, Ulf Rädler, Lutz Schmitt and Robert Tampé

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200200455

      Thumbnail image of graphical abstract

      Plucking out protein pairs: The synthesis and potential applications of a metal-chelating amino acid within a polypeptide (see scheme) are described. This building block binds its target selectively and can be used in biochemical tweezers to control protein–protein interactions and in the design of new peptide-based interaction pairs and sensors.

    14. Antibiotic and Hemolytic Activity of a β23 Peptide Capable of Folding into a 12/10-Helical Secondary Structure (pages 1345–1347)

      Per I. Arvidsson, Neil S. Ryder, H. Markus Weiss, Gerhard Gross, Olivier Kretz, Ralph Woessner and Dieter Seebach

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300698

      Active peptide helices: The β-nonapeptide H-β3HPhe-β2HVal-β3HPhe-β2HLeu-β3HLys-β2HLeu-β3HLys-β2HLeu-β3HPhe-OH with alternating β2- and β3-amino-acid residues has been tested for antibiotic and hemolytic activities. This represents the first case of biomimetic activity of a “mixed” β32-peptide.

    15. Icosahedral Virus Particles as Polyvalent Carbohydrate Display Platforms (pages 1348–1351)

      Krishnaswami S. Raja, Qian Wang and M. G. Finn

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300759

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      Sugar-coated viruses behave as large dendrimeric poly(carbohydrates). Readily prepared from the icosahedral cowpea mosaic virus (one-twelfth of the structure of this scaffold is shown here, with attachment points in yellow) and electrophilic sugar derivatives, the resulting particles bind strongly to the lectin concanavalin-A, forming cross-linked networks. Measurements of binding strength demonstrate effective polyvalencies comparable to the most potent dendrimer- and polymer-based systems reported to date, with the added advantage of near atomic-resolution control over structure.

    16. Cyclopropane Fatty Acid Synthase from Escherichia coli: Enzyme Purification and Inhibition by Vinylfluorine and Epoxide-Containing Substrate Analogues (pages 1352–1356)

      Erich J. Molitor, Beth M. Paschal and Hung-wen Liu

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200300767

      Thumbnail image of graphical abstract

      Biosynthesis of cyclopropane fatty acid (CFA) found in the lipids of many eubacteria is catalyzed by CFA synthase as per the scheme. An efficient method has been developed that allows significant quantities of phospholipid-free CFA synthase to be purified with high purity and good activity. Two phospholipid derivatives were synthesized as mechanistic probes for CFA synthase. The fact that both compounds are inhibitors rather than substrates for this enzyme is consistent with a mechanism involving carbocation intermediate/transition state.

    17. Preview: ChemBioChem 12/2003 (page 1360)

      Version of Record online: 24 NOV 2003 | DOI: 10.1002/cbic.200390126