ChemBioChem

Cover image for Vol. 9 Issue 18

December 15, 2008

Volume 9, Issue 18

Pages 2897–3093

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
    1. Cover Picture: Extremely Tight Binding of a Ruthenium Complex to Glycogen Synthase Kinase 3 (ChemBioChem 18/2008) (page 2897)

      G. Ekin Atilla-Gokcumen, Nicholas Pagano, Craig Streu, Jasna Maksimoska, Panagis Filippakopoulos, Stefan Knapp and Eric Meggers

      Version of Record online: 9 DEC 2008 | DOI: 10.1002/cbic.200890070

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      The cover picture shows the binding of a ruthenium half-sandwich complex to the ATP binding site of glycogen synthase kinase 3 (GSK-3) and how its structure and potency evolved from a brief structure–activity relationship. With a binding constant (Ki) of, at most, 5 pM, this organometallic compound is several orders of magnitude more potent than the natural product staurosporine, which itself served as an inspiration for the design. The crystal structure of the organoruthenium inhibitor with GSK-3 demonstrates that the metal itself is not involved in any direct interactions with the active site of GSK-3, but solely serves as a structural center. Further details can be found in the article by E. Meggers, et al. on p. 2933 ff.

  2. Graphical Abstract

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
  3. News

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
  4. Minireviews

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
    1. Chemical Biology Approaches to Probe the Proteome (pages 2913–2919)

      Huib Ovaa and Fred van Leeuwen

      Version of Record online: 29 OCT 2008 | DOI: 10.1002/cbic.200800454

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      Dissecting the proteome. Platforms are available to investigate the events that occur from gene to protein. These, combined with our ability to manipulate the genome and proteome by RNAi and chemical probes alike, are transforming the biomedical field. The opportunities arising to investigate disease, develop therapies and to explore the proteome with chemistry-based approaches are rapidly increasing in number and will be discussed here.

    2. Allosteric Regulation of Proteases (pages 2920–2928)

      Patrick Hauske, Christian Ottmann, Michael Meltzer, Michael Ehrmann and Markus Kaiser

      Version of Record online: 19 NOV 2008 | DOI: 10.1002/cbic.200800528

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      An alternative grip on proteases: Allosteric small-molecule regulation of proteases opens up new opportunities for specific control of cellular proteolytic activities and complements existing active-site-directed approaches. This review discusses natural proteinaceous and designed small molecules that act as allosteric protease regulators, highlighting a general mechanism that accounts for allostery in proteases.

  5. Highlight

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
    1. Taking a Closer Look at Fatty Acid Biosynthesis (pages 2929–2931)

      Kira J. Weissman

      Version of Record online: 17 NOV 2008 | DOI: 10.1002/cbic.200800671

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      Crystal structure of a multienzyme: Ban et al. recently reported a breakthrough in understanding fatty acid synthesis in animals. Determination of a 3.2 Å crystal structure of porcine fatty acid synthase (FAS) reveals a multienzyme of startling architectural complexity.

  6. Communications

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
    1. Extremely Tight Binding of a Ruthenium Complex to Glycogen Synthase Kinase 3 (pages 2933–2936)

      G. Ekin Atilla-Gokcumen, Nicholas Pagano, Craig Streu, Jasna Maksimoska, Panagis Filippakopoulos, Stefan Knapp and Eric Meggers

      Version of Record online: 26 NOV 2008 | DOI: 10.1002/cbic.200800489

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      Perfect match: An organoruthenium complex with at most a low picomolar binding constant for glycogen synthase kinases 3 is reported, whose binding to the ATP-binding site has been analyzed by X-ray crystallography. The complex, (RRu)-NP549, is one of the most potent protein kinase inhibitors reported to date, almost four orders of magnitude more potent than the related natural product staurosporine.

      Corrected by:

      Corrigendum: Extremely Tight Binding of a Ruthenium Complex to Glycogen Synthase Kinase 3

      Vol. 10, Issue 2, 198, Version of Record online: 15 JAN 2009

    2. Gene Silencing in Mammalian Cells with Light-Activated Antisense Agents (pages 2937–2940)

      Douglas D. Young, Hrvoje Lusic, Mark O. Lively, Jeffrey A. Yoder and Alexander Deiters

      Version of Record online: 19 NOV 2008 | DOI: 10.1002/cbic.200800627

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      On and off the spot: The spatio-temporal light-activation of gene silencing was achieved through the complete inactivation of phosphorothioate antisense agents by installing light-removable (caged) groups at specific sites, as illustrated here. Full antisense activity was restored through a brief irradiation with UV light at 365 nm.

    3. Consistent Bioactive Conformation of the Neu5Acα(2[RIGHTWARDS ARROW]3)Gal Epitope Upon Lectin Binding (pages 2941–2945)

      Anirban Bhunia, Oliver Schwardt, Heiko Gäthje, Gan-Pan Gao, Soerge Kelm, Andrew J. Benie, Milos Hricovini, Thomas Peters and Beat Ernst

      Version of Record online: 10 OCT 2008 | DOI: 10.1002/cbic.200800458

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      Get to NOE MAG: Partial structures of GQ1bα, the natural ligand of the myelin-associated glycoprotein (MAG), have been synthesized and subjected to NOE experiments to determine their bioactive conformations. The experiments show that the flexible α(2[RIGHTWARDS ARROW]3)-glycosidic linkage between N-acetylneuraminic acid and galactose present in all ligands adopts a “sialyl Lewisx-type” binding mode. This information is valuable for the future design of conformationally preorganized MAG inhibitors.

    4. Binding Epitopes of Gangliosides to their Neuronal Receptor, Myelin-Associated Glycoprotein, from Saturation Transfer Difference NMR (pages 2946–2949)

      So-Young Shin, Heiko Gäthje, Oliver Schwardt, Gan-Pan Gao, Beat Ernst, Soerge Kelm and Bernd Meyer

      Version of Record online: 28 NOV 2008 | DOI: 10.1002/cbic.200800485

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      MAGnificent analysis to remove ambiguity: The binding epitopes of tri- and tetrasaccharide ligands in their interactions with the myelin-associated glycoprotein (MAG) have been studied by using saturation transfer difference NMR, in which the signal intensities can help to resolve overlapped HSQC signals. In the figure, the signals of the protons with the closest proximity to the protein are shown in red (30–60 %) or blue (61–100 %).

    5. Nanomolar Heparin Detection with an Artificial Enzyme (pages 2950–2953)

      Laurent Vial and Pascal Dumy

      Version of Record online: 14 NOV 2008 | DOI: 10.1002/cbic.200800420

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      Detecting heparin: We report a new fluorescent approach to the detection and quantification of the biologically relevant molecule heparin. We designed and prepared a cyclic peptide that is able to catalyse the hydrolysis of a fluorogenic anionic ester (green) under low-concentration conditions. Then we demonstrated that the inhibition of this artificial enzyme (grey) by heparin (red) allows its fluorescent sensing with a remarkable sensitivity of 13 nM.

    6. Engineering of Thermus thermophilus Cytochrome c552: Thermally Tolerant Artificial Peroxidase* (pages 2954–2957)

      Hiroshi Nakajima, Yusuke Ichikawa, Yuh Satake, Nobuyuki Takatani, Soumen Kanti Manna, Jitumani Rajbongshi, Shyamalava Mazumdar and Yoshihito Watanabe

      Version of Record online: 12 NOV 2008 | DOI: 10.1002/cbic.200800599

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      Customizing enzymes: We demonstrate that cytochrome c552 (Cyt c552) from Thermus thermophilus HB8 can be transformed into a thermally tolerant peroxidase by a design process modeled on the catalytic mechanism of peroxidases. At temperatures above 50 °C, the enzymatic activity of the engineered Cyt c552 surpasses that of a myoglobin variant that is known to exhibit the highest activity among artificial peroxidases.

    7. Segmental Isotopic Labelling of a Multidomain Protein by Protein Ligation by Protein Trans-Splicing (pages 2958–2961)

      Mikko Muona, A. Sesilja Aranko and Hideo Iwai

      Version of Record online: 21 NOV 2008 | DOI: 10.1002/cbic.200800604

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      Structure–function relationships of intact multidomain proteins: Segmental isotopic labelling of multidomain proteins could open a new avenue for studying particular domains in intact proteins, because it could simplify the NMR spectra through the incorporation of stable isotopes in a region-specific manner. We have demonstrated that the necessary protein ligation can be easily achieved both in vivo and in vitro by protein trans-splicing.

    8. Improved Catalytic Activity of a Purified Multienzyme from a Modular Polyketide Synthase after Coexpression with Streptomyces Chaperonins in Escherichia coli. (pages 2962–2966)

      Lorena Betancor, María-José Fernández , Kira J. Weissman  and Peter F. Leadlay

      Version of Record online: 19 NOV 2008 | DOI: 10.1002/cbic.200800475

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      Folding helpers: Coexpression of Streptomyces coelicolor chaperonins GroEL1, GroEL2 and GroES with an actinomycete-derived polyketide synthase multienzyme in Escherichia coli has beneficial effects on yield, folding and specific activity of the purified enzyme. The results strongly suggest the utility of chaperones derived from polyketide-producing actinomycete bacteria in optimising the recombinant production of PKS proteins in E. coli for detailed studies of structure and function.

  7. Full Papers

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
    1. Analysis of Specific Mutants in the Lasalocid Gene Cluster: Evidence for Enzymatic Catalysis of a Disfavoured Polyether Ring Closure (pages 2967–2975)

      Luke Smith, Hui Hong, Jonathan B. Spencer  and Peter F. Leadlay

      Version of Record online: 24 NOV 2008 | DOI: 10.1002/cbic.200800585

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      Baldwin's rules bent: The biosynthesis of the polyether ionophore lasalocid in Streptomyces lasaliensis involves a kinetically disfavoured ring closure to form a six-membered tetrahydropyran. In a mutant lacking the novel epoxide hydrolase LasB, the intermediate instead forms the five-membered ring product predicted by Baldwin's rules; this shows the key role of LasB in stereocontrol.

    2. Polymerase Amplification, Cloning, and Gene Expression of Benzo-Homologous “yDNA” Base Pairs (pages 2976–2980)

      Jijumon Chelliserrykattil, Haige Lu, Alex H. F. Lee and Eric T. Kool

      Version of Record online: 3 DEC 2008 | DOI: 10.1002/cbic.200800339

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      Large bases encoding information: Here, we study whether DNA base pairs widened by addition of benzene can correctly store and transfer genetic information. Although the efficiency and selectivity in replication are low, the bases yT and yC were correctly amplified by PCR a substantial fraction of the time. Moreover, they correctly encoded amino acids in green fluorescent protein in bacterial cells.

    3. 7-Azidomethoxy-Coumarins as Profluorophores for Templated Nucleic Acid Detection (pages 2981–2988)

      Raphael M. Franzini and Eric T. Kool

      Version of Record online: 26 NOV 2008 | DOI: 10.1002/cbic.200800507

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      Lighten up! 7-Azidomethoxycoumarins constitute phosphine-sensitive profluorophores. A DNA-templated Staudinger reduction removes the azidomethyl substituent and activates coumarin fluorescence. This method detects nucleic acid sequences with significant single mismatch discrimination and amplification of the fluorescence signal.

    4. Total Synthesis of desB30 Insulin Analogues by Biomimetic Folding of Single-Chain Precursors (pages 2989–2996)

      A. Pernille Tofteng, Knud J. Jensen, Lauge Schäffer and Thomas Hoeg-Jensen

      Version of Record online: 26 NOV 2008 | DOI: 10.1002/cbic.200800430

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      Chain reaction: The total chemical synthesis of desB30 insulin analogues by Fmoc-based, solid-phase synthesis of single-chain precursors that folded to give yields of up to 25 % (11 % after purification) and that were transformed into two-chain insulin by a protease from Achromobacter lyticus is reported. The overall insulin yield was as much as 6 %, and the method was not labour intensive. An example of insulin with the unnatural amino acid α-aminoisobutyric acid (Aib) is shown.

    5. Phenylnannolones A–C: Biosynthesis of New Secondary Metabolites from the Myxobacterium Nannocystis exedens (pages 2997–3003)

      Birgit Ohlendorf, Stefan Leyers, Anja Krick, Stefan Kehraus, Michael Wiese and Gabriele M. König

      Version of Record online: 28 NOV 2008 | DOI: 10.1002/cbic.200800434

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      Outsiders giving insights: Myxobacteria are talented producers of bioactive secondary metabolites. However, Nannocystis spp. have hardly been investigated. Phenylnannolones from Nannocystis exedens, as illustrated here, represent a unique type of polyketide and reverse the multidrug resistance of cancer cells. The biosynthesis of the phenylnannolones comprises novel biochemical reactions.

    6. Cooperative Biosynthesis of Trisporoids by the (+) and (−) Mating Types of the Zygomycete Blakeslea trispora (pages 3004–3012)

      Doreen Schachtschabel, Anja David, Klaus-Dieter Menzel, Christine Schimek, Johannes Wöstemeyer and Wilhelm Boland

      Version of Record online: 26 NOV 2008 | DOI: 10.1002/cbic.200800477

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      A chemical romance: Trisporic acids (TSAs) control the sexual reproduction of opposite mating types of many zygomycetes fungi. Cultures of Blakeslea trispora were supplemented with a series of deuterium-labeled apocarotenoid precursors. The isolated metabolites allowed for the reconstruction of the biosynthetic sequence between β-carotene and the different series of TSAs.

    7. Investigation of Biosynthetic Pathways to Hydroxycoumarins During Post-Harvest Physiological Deterioration in Cassava Roots by Using Stable Isotope Labelling (pages 3013–3022)

      Soad A. L. Bayoumi, Michael G. Rowan, John R. Beeching and Ian S. Blagbrough

      Version of Record online: 26 NOV 2008 | DOI: 10.1002/cbic.200800515

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      Rooting out the right pathway: Isotopic labelling studies show that cinnamate goes via ferulate to scopoletin, whereas esculetin is biosynthesised from umbelliferone in cassava roots during post-harvest physiological deterioration. The lactonisation step proceeds by ortho-hydroxylation and not via a proposed spirolactone-dienone.

    8. Importance of Translation–Replication Balance for Efficient Replication by the Self-Encoded Replicase (pages 3023–3028)

      Norikazu Ichihashi, Tomoaki Matsuura, Hiroshi Kita, Kazufumi Hosoda, Takeshi Sunami, Koji Tsukada and Tetsuya Yomo

      Version of Record online: 19 NOV 2008 | DOI: 10.1002/cbic.200800518

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      Express yourself: We have devised a self-encoding system in which RNA was replicated by the self-encoded RNA replicase (Rep) produced by the translation reaction, and the ribosome (Rib) and replicase competed for the RNA. We evaluated the competition effect for RNA replication by constructing a kinetic model, as illustrated. The results indicated that the balance between translation and replication was critical for an efficient self-encoded system.

    9. Orientation of the Monomeric Porin OmpG in Planar Lipid Bilayers (pages 3029–3036)

      Min Chen, Qiu-Hong Li and Hagan Bayley

      Version of Record online: 14 NOV 2008 | DOI: 10.1002/cbic.200800444

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      The orientations of single OmpG pores in planar lipid bilayers were determined from the sidedness of the response of an extracellular disulfide bond to dithiothreitol (DTT). With this knowledge, the binding of a cyclodextrin adapter presented to OmpG from the extracellular or periplasmic side was investigated. The information on the interaction between the cyclodextrin and OmpG serves to advance the use of OmpG as a biosensor.

    10. Differential Inhibitory Activities and Stabilisation of DNA Aptamers against the SARS Coronavirus Helicase (pages 3037–3045)

      Ka To Shum and Julian A. Tanner

      Version of Record online: 21 NOV 2008 | DOI: 10.1002/cbic.200800491

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      Non-Hoogsteen or Hoogsteen? DNA aptamers evolved against the SCV helicase were split into two classes: non-G-quadruplex and G-quadruplex. The non-G-quadruplex aptamers inhibited the helicase activities but the G-quadruplex aptamers did not. Understanding this structure-based inhibition will be critical for further aptamer development against helicases.

    11. Photocontrollable Peptide-Based Switches Target the Anti-Apoptotic Protein Bcl-xL (pages 3046–3054)

      Sabine Kneissl, E. Joel Loveridge, Christopher Williams, Matthew P. Crump and Rudolf K. Allemann

      Version of Record online: 14 NOV 2008 | DOI: 10.1002/cbic.200800502

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      Photocontrol of Bcl-xLbinding affinity has been achieved with short peptides alkylated with azobenzene crosslinkers. Helix-stabilized peptides exhibited up to 20-fold enhancements in affinity relative to their helix-destabilized forms, and more than 200-fold selectivity for binding to Bcl-xL over Hdm2. Such photocontrollable peptide-based switches may be used to interfere specifically with biomacromolecular interactions.

    12. Controlled Production of Amyloid β Peptide from a Photo-Triggered, Water-Soluble Precursor “Click Peptide“ (pages 3055–3065)

      Atsuhiko Taniguchi, Mariusz Skwarczynski, Youhei Sohma, Takuma Okada, Keisuke Ikeda, Halan Prakash, Hidehito Mukai, Yoshio Hayashi , Tooru Kimura, Shun Hirota, Katsumi Matsuzaki and Yoshiaki Kiso

      Version of Record online: 24 NOV 2008 | DOI: 10.1002/cbic.200800503

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      In situ production of amyloid β (Aβ) 142: A novel photo-“click peptide” has nearly 100-fold higher water solubility than Aβ1–42 and no self-assembling tendencies. The click peptide is able to produce intact Aβ1–42 quickly under physiological conditions (pH 7.4, 37 °C) upon photoirradiation followed by an O–N intramolecular acyl migration.

    13. Post-translational Modification in Microviridin Biosynthesis (pages 3066–3073)

      Benjamin Philmus, Guntram Christiansen, Wesley Y. Yoshida and Thomas K. Hemscheidt

      Version of Record online: 26 NOV 2008 | DOI: 10.1002/cbic.200800560

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      Tales of the unexpected: Microviridin K (1) is a potent elastase inhibitor. It is biosynthesized from a linear prepeptide that is triply cross-linked by ester and amide bonds between the ω-functional groups of glutamic acid residues and serine, threonine and lysine. This unprecedented post-translational modification process and the N-terminal acetylation have been reconstituted in vitro.

    14. Tubulin Photoaffinity Labeling with Biotin-Tagged Derivatives of Potent Diketopiperazine Antimicrotubule Agents (pages 3074–3081)

      Yuri Yamazaki , Kyoko Kohno, Hiroyuki Yasui, Yoshiaki Kiso, Miki Akamatsu, Benjamin Nicholson, Gordafaried Deyanat-Yazdi, Saskia Neuteboom, Barbara Potts, G. Kenneth Lloyd and Yoshio Hayashi

      Version of Record online: 14 NOV 2008 | DOI: 10.1002/cbic.200800317

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      DKP photoaffinity probes: Based on a new vascular-disrupting agent, NPI-2358, biotin-tagged photoaffinity probes with antimicrotubule activity were designed and synthesized. A tubulin photoaffinity labeling study revealed that the synthesized compounds are useful chemical probes for NPI-2358.

  8. Conference Report

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
    1. EMBL Conference on Chemical Biology 2008 (pages 3083–3086)

      Felix Hausch and Christian F. W. Becker

      Version of Record online: 12 NOV 2008 | DOI: 10.1002/cbic.200800711

  9. Book Reviews

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
    1. Therapeutic Oligonucleotides. Edited by Jens Kurreck. (pages 3087–3088)

      Carine Giovannangeli and Tula Saison-Behmoaras

      Version of Record online: 9 DEC 2008 | DOI: 10.1002/cbic.200800738

  10. Preview

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
    1. You have free access to this content
      Preview: ChemBioChem 1/2009 (page 3092)

      Version of Record online: 9 DEC 2008 | DOI: 10.1002/cbic.200890073

  11. Index

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireviews
    6. Highlight
    7. Communications
    8. Full Papers
    9. Conference Report
    10. Book Reviews
    11. Preview
    12. Index
    1. Index: 2008 (page 3093)

      Version of Record online: 9 DEC 2008 | DOI: 10.1002/cbic.200812345

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