Cover image for ChemBioChem

February 4, 2005

Volume 6, Issue 2

Pages 209–450

    1. Cover Picture: A New Chemical Probe for Proteomics of Carbohydrate-Binding Proteins (ChemBioChem 2/2005) (page 209)

      Lluis Ballell, Kirstin J. Alink, Monique Slijper, Cees Versluis, Rob M. J. Liskamp and Roland J. Pieters

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200590003

      The cover picture shows how galectins are selected from a mixture of proteins by a novel probe. The probe noncovalently binds the medicinally relevant galectins, and its photoaffinity label covalently captures the protein. The captured protein is visualized by a fluorescent dye that is introduced by chemoselective 1,2,3-triazole formation or "click" chemistry. The methodology represents a step towards comparative quantification of the galectin amounts in proteomes, which is relevant, for example, for prognosis with respect to the malignancy of tissues. Despite the low affinities in protein–carbohydrate interactions, the probe shown is able to select the galectins from a mixture of four proteins. For more information, see the article by R. J. Pieters et al on p. 291 ff.

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      Synthesis and Degradation of Nucleobases and Nucleic Acids by Formamide in the Presence of Montmorillonites (page 218)

      Raffaele Saladino, Claudia Crestini, Umberto Ciambecchini, Fabiana Ciciriello, Giovanna Costanzo and Ernesto Di Mauro

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200590005

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      High-Content Screening and Profiling of Drug Activity in an Automated Centrosome-Duplication Assay (page 218)

      Zachary E. Perlman, Timothy J. Mitchison and Thomas U. Mayer

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200590007

    4. Molecular Machines for Protein Degradation (pages 222–256)

      Michael Groll, Matthias Bochtler, Hans Brandstetter, Tim Clausen and Robert Huber

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200400313

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      How to have a break down. One of the most precisely regulated processes in living cells is intracellular protein degradation. Here, the current state of knowledge about protein-degradation systems is summarised, with the focus on the proteasome (see structure), HslVU, Tricorn protease and its interacting factors and DegP. The structural information about these protein complexes allows the mode of action of natural and synthetic inhibitors to be studied. Some of these compounds may find therapeutic applications in contemporary medicine.

    5. Duplex RNA-Binding Enzymes: Headliners from Neurobiology, Virology, and Development (pages 257–266)

      Peter A. Beal

      Version of Record online: 11 JAN 2005 | DOI: 10.1002/cbic.200400303

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      Duplex RNA-binding proteins are key players in a number of fields, including neurobiology, virology, and development. In this minireview, five human enzymes are discussed that bind duplex RNA through double-stranded RNA-binding motifs, including RNA-editing adenosine deaminases. Also highlighted are opportunities for advancing our understanding of these fascinating enzymes by chemical biology.

    6. The Biosynthesis of Vancomycin-Type Glycopeptide Antibiotics—A Model for Oxidative Side-Chain Cross-Linking by Oxygenases Coupled to the Action of Peptide Synthetases (pages 267–272)

      Daniel Bischoff, Bojan Bister, Marcelo Bertazzo, Volker Pfeifer, Efthimia Stegmann, Graeme J. Nicholson, Simone Keller, Stefan Pelzer, Wolfgang Wohlleben and Roderich D. Süssmuth

      Version of Record online: 13 JAN 2005 | DOI: 10.1002/cbic.200400328

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      Model mutants. The biosynthesis of glycopeptide antibiotics must be understood before it can be reprogrammed to generate altered antibiotics. Based on a detailed HPLC-ESI-MS analysis of linear and cyclic peptide intermediates of balhimycin biosynthesis mutants, a new model for glycopeptide assembly is suggested (see figure). We propose that the three central oxidative cyclizations by P450-dependant monooxygenases occur during peptide assembly before cleavage from the nonribosomal peptide synthetase complex.

    7. Integrin α5β1 Ligands: Biological Evaluation and Conformational Analysis (pages 272–276)

      Dunja Zimmermann, Eckhart W. Guthöhrlein, Miroslav Malešević, Katherina Sewald, Lutz Wobbe, Carolin Heggemann and Norbert Sewald

      Version of Record online: 11 JAN 2005 | DOI: 10.1002/cbic.200400279

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      Breaking up is easy. Integrin α5β1 is a cell-surface receptor involved in many physiological and pathological processes. Small cyclic peptides can influence the interaction between this receptor and its natural ligand, fibronectin. The peptide shown, c-(-Arg-Gly-Asp-D-Phe-Val-β-Ala-), can bind α5β1 with submicromolar affinity. A conformational analysis of the peptide provided information on the structural properties responsible for binding to α5β1.

    8. Total Synthesis and Biological Activity of 13,14-Dehydro-12-Oxo-Phytodienoic Acids (Deoxy-J1-Phytoprostanes) (pages 276–280)

      Mazhar Iqbal, Paul Evans, Agustí Lledó, Xavier Verdaguer, Miquel A. Pericàs, Antoni Riera, Christiane Loeffler, Alok K. Sinha and Martin J. Mueller

      Version of Record online: 28 DEC 2004 | DOI: 10.1002/cbic.200400259

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      Archetype lipid signals in plants. Non-enzymatic oxidation of linolenate yields a series of prostaglandin-like stress metabolites including racemic deoxy-J1-phytoprostanes (1) that are structurally related to 12-oxo-phytodienoic acid (2). Naturally occurring isomers of 1 were prepared by total synthesis and tested in three bioassay systems to reveal potent jasmonate-like activities.

    9. The Conformation of B18 Peptide in the Presence of Fluorinated and Alkylated Nanoparticles (pages 280–283)

      Sandra Rocha, Andreas F. Thünemann, M. Carmo Pereira, Manuel A. N. Coelho, Helmuth Möhwald and Gerald Brezesinski

      Version of Record online: 11 JAN 2005 | DOI: 10.1002/cbic.200400177

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      Refolding the sheets. Fluorinated nanoparticles with a diameter of 4 nm were found to induce α-helix-rich structures in the fibril-forming peptide, B18. In contrast, the alkylated analogues induced aggregation and β-sheet formation (see CD spectra). Fluorinated particles are proposed to be potential candidates for the stabilization of protein monomeric structures.

    10. The Selectivity for Cysteine over Serine in Coenzyme A Biosynthesis (pages 284–286)

      Erick Strauss and Tadhg P. Begley

      Version of Record online: 9 DEC 2004 | DOI: 10.1002/cbic.200400340

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      The cysteine-derived thiol group of coenzyme A (CoA) is the key functional group involved in catalysis by this cofactor. Since CoA analogues are potent antibiotics, it is critical that CoA biosynthetic enzymes show high selectivity for the incorporation of cysteine over closely related amino acids such as serine (see scheme). In this study, we determine that the cysteine/serine selectivity ratio in CoA biosynthesis is >5.0×105, and localize this selectivity to two enzymes in the pathway.

    11. Small-Molecule Inhibitors and Probes for Ubiquitin- and Ubiquitin-Like-Specific Proteases (pages 287–291)

      Anna Borodovsky, Huib Ovaa, Wim J. N. Meester, Emily S. Venanzi, Matthew S. Bogyo, Brian G. Hekking, Hidde L. Ploegh, Benedikt M. Kessler and Herman S. Overkleeft

      Version of Record online: 13 JAN 2005 | DOI: 10.1002/cbic.200400236

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      There's always a catch. The post-translational modification of proteins with ubiquitin (Ub) or ubiquitin-like (Ubl) modifiers is an important signal in the regulation of a variety of biological processes, such as degradation and regulation of gene expression. Here we report the synthesis of a panel of peptide vinyl sulfones (see scheme) harboring various portions of the Ub C terminus by using a safety-catch linker. Depending on their length, such compounds can efficiently target Ubl-specific proteases.

    12. A New Chemical Probe for Proteomics of Carbohydrate-Binding Proteins (pages 291–295)

      Lluis Ballell, Kirstin J. Alink, Monique Slijper, Cees Versluis, Rob M. J. Liskamp and Roland J. Pieters

      Version of Record online: 2 DEC 2004 | DOI: 10.1002/cbic.200400209

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      Selective capture of galectins, while leaving other proteins untouched, was achieved by activating photoaffinity labels that were precisely positioned on noncovalently bound carbohydrate ligands. The labelled proteins were visualised in-gel by “clicking-on” a rhodamine moiety afterwards.

    13. Specific 3′-Terminal Modification of DNA with a Novel Nucleoside Analogue that Allows a Covalent Linkage of a Nuclear Localization Signal and Enhancement of DNA Stability (pages 297–303)

      Yutaka Ikeda, Shun-ichi Kawahara, Koichi Yoshinari, Satoshi Fujita and Kazunari Taira

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200400142

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      More interference. We report a straightforward method for site-specific modification of long double-stranded DNA with bioactive molecules. We added a nuclear localization signal peptide to the 3′-termini of 350 bp-long DNA that encodes short hairpin RNA, and these modifications resulted in enhancement of the suppressive activity of RNA interference.

    14. Asprich: A Novel Aspartic Acid-Rich Protein Family from the Prismatic Shell Matrix of the Bivalve Atrina rigida (pages 304–314)

      Bat-Ami Gotliv, Naama Kessler, Jan L. Sumerel, Daniel E. Morse, Noreen Tuross, Lia Addadi and Steve Weiner

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200400221

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      Acidic macromolecules are key components in biological mineralization. We report the sequences of an Asp-rich protein family located in the calcitic prismatic layer of the shell of the mollusk Atrina rigida (see picture). This novel protein family contains unique sequence domains that shed light on the nature of acidic proteins in mineralized tissues

    15. Selection of an Active Enzyme by Phage Display on the Basis of the Enzyme's Catalytic Activity in vivo (pages 315–321)

      Satoshi Fujita, Takashi Taki and Kazunari Taira

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200400215

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      Caught in the act. The figure shows the schematic representation of the system for in vivo selection of an enzyme on the basis of catalytic activity and the use of phage display. A library containing phagemids is introduced into E. coli host cells. The host cells are then infected with phage. If biotin protein ligase (BPL) is expressed in the E. coli, biotin-tag-peptide (Btag) is biotinylated by BPL. Biotinylated phage particles are then captured on avidin resin.

    16. A Biosynthetic Pathway to Isovaleryl-CoA in Myxobacteria: The Involvement of the Mevalonate Pathway (pages 322–330)

      Taifo Mahmud, Silke C. Wenzel, Eva Wan, Kwun Wah Wen, Helge B. Bode, Nikolaos Gaitatzis and Rolf Müller

      Version of Record online: 27 DEC 2004 | DOI: 10.1002/cbic.200400261

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      Branch line. A biosynthetic pathway (see scheme) branching from the mevalonate pathway and providing starter units for branched-chain fatty acid and secondary metabolite biosynthesis has been identified in strains of the myxobacterium Stigmatella aurantiaca. The shunt pathway most likely also operates reversibly providing an alternative source for the monomers of isoprenoid biosynthesis in myxobacteria. (Picture courtesy of H. Reichenbach.)

    17. Exploring the Active-Site of a Rationally Redesigned Lipase for Catalysis of Michael-Type Additions (pages 331–336)

      Peter Carlqvist, Maria Svedendahl, Cecilia Branneby, Karl Hult, Tore Brinck and Per Berglund

      Version of Record online: 3 DEC 2004 | DOI: 10.1002/cbic.200400213

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      New lipase reactions: Michael-type additions of various thiols to α,β-unsaturated carbonyl compounds were successfully performed in an organic solvent catalyzed by a rationally redesigned mutant of Candida antarctica lipase B with the active-site serine replaced. The catalytic reaction was initially explored by quantum chemical calculations.

    18. Transport Of Surface-Modified Nanoparticles Through Cell Monolayers (pages 337–345)

      Annette M. Koch, Fred Reynolds, Hans P. Merkle, Ralph Weissleder and Lee Josephson

      Version of Record online: 13 JAN 2005 | DOI: 10.1002/cbic.200400174

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      The ability of Tat-like peptides to enhance nanoparticle transport is demonstrated. The figure depicts the transport of a peptide–nanoparticle conjugate (peptide is green rectangle attached to the brown, round nanoparticle) through a cell monolayer.

    19. High-Throughput Mass-Spectrometry Monitoring for Multisubstrate Enzymes: Determining the Kinetic Parameters and Catalytic Activities of Glycosyltransferases (pages 346–357)

      Min Yang, Melissa Brazier, Robert Edwards and Benjamin G. Davis

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200400100

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      Colour screen test. A novel high-throughput ES-TOF mass spectrometry method allows not only broad-ranging screening of the acceptor and donor specificities of glycosyltransferases but also the determination of full multisubstrate kinetic parameters. The green/amber/red screen is based on the mass ion abundance of product (see figure).

    20. Multivalent HSA Conjugates of 3′-Sialyllactose are Potent Inhibitors of Adenoviral Cell Attachment and Infection (pages 358–364)

      Susanne M. C. Johansson, Niklas Arnberg, Mikael Elofsson, Göran Wadell and Jan Kihlberg

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200400227

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      A pinch of sugar helps the swelling go down. The adenovirus of serotype Ad37 causes EKC, a severe ocular infection. Synthetic, multivalent 3′-sialyllactose HSA conjugates, such as 1, effectively prevented viral cell attachment and subsequent infection. These neoglycoconjugates may have potential for combating EKC.

    21. Novel Insights into Siderophore Formation in Myxobacteria (pages 365–374)

      Nikolaos Gaitatzis, Brigitte Kunze and Rolf Müller

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200400206

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      Iron chelator biosynthesis. The myxochelins are catecholate-type siderophores produced by a number of myxobacteria including Stigmatella aurantiaca and Sorangium cellulosum. Both corresponding biosynthetic gene clusters have been identified and, as shown in the scheme, in addition to the myxochelin A biosynthetic complex, the aminotransferase MxcL is required to form myxochelin B.

    22. Structure and Biosynthesis of Myxochromides S1–3 in Stigmatella aurantiaca: Evidence for an Iterative Bacterial Type I Polyketide Synthase and for Module Skipping in Nonribosomal Peptide Biosynthesis (pages 375–385)

      Silke C. Wenzel, Brigitte Kunze, Gerhard Höfle, Barbara Silakowski, Maren Scharfe, Helmut Blöcker and Rolf Müller

      Version of Record online: 13 JAN 2005 | DOI: 10.1002/cbic.200400282

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      Novel microbial metabolites found by genetic screening. New myxochromides, such as the one shown here, have been isolated from the myxobacterium Stigmatella aurantiaca. An earlier mutagenesis approach established that a hybrid polyketide synthase/nonribosomal peptide synthetase was responsible for the production of these formerly unknown metabolites. Structural elucidation in correlation with analysis of the sequenced genes reveals several striking and unusual biosynthetic features.

    23. The Functional Role of Selenocysteine (Sec) in the Catalysis Mechanism of Large Thioredoxin Reductases: Proposition of a Swapping Catalytic Triad Including a Sec-His-Glu State (pages 386–394)

      Wolfgang Brandt and Ludger A. Wessjohann

      Version of Record online: 13 JAN 2005 | DOI: 10.1002/cbic.200400276

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      Just a Sec. What is the importance of a selenocysteine (Sec, U) rather than cysteine in selenoproteins? For the first time, based on modelling, DFT calculations and previous experimental results, an explanation for the role of Sec in large thioredoxin reductases is given.

    24. Kinetics Study of Bungarus fasciatus Venom Acetylcholinesterase Immobilised on a Langmuir–Blodgett Proteo-Glycolipidic Bilayer (pages 395–404)

      Stéphanie Godoy, Sébastien Violot, Paul Boullanger, Marie-Noëlle Bouchu, Béatrice D. Leca-Bouvier, Loïc J. Blum and Agnès P. Girard-Egrot

      Version of Record online: 13 JAN 2005 | DOI: 10.1002/cbic.200400277

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      Directed enzyme immobilisation on the surface of a glycolipidic bilayer. The main goal of this study is to develop a molecular assembly capable of orientating AChE in order to access the intrinsic biocatalytic behaviour of the enzyme in a biomimetic situation

    25. A New Type of Metalloprotein: The Mo Storage Protein from Azotobacter vinelandii Contains a Polynuclear Molybdenum–Oxide Cluster (pages 405–413)

      Dirk Fenske, Manuel Gnida, Klaus Schneider, Wolfram Meyer-Klaucke, Jörg Schemberg, Volker Henschel, Anne-Katrin Meyer, Arndt Knöchel and Achim Müller

      Version of Record online: 13 JAN 2005 | DOI: 10.1002/cbic.200400263

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      Saving up molybdenum: The first comprehensive characterization of the Mo storage protein (see structure), which contains a nanosized molybdenum–oxide-based cluster and shows interdisciplinary aspects ranging from inorganic chemistry to evolutionary problems, reveals that the amino acid sequence is not related to any other known molybdoprotein. The unique binding and release mechanisms of the “molybdenum” open a new chapter in metal storage in biology.

    26. Induction of DNA-Double-Strand Breaks by Auger Electrons from 99mTc Complexes with DNA-Binding Ligands (pages 414–421)

      Pascal Häfliger, Nikos Agorastos, Bernhard Spingler, Oleg Georgiev, Giampietro Viola and Roger Alberto

      Version of Record online: 13 JAN 2005 | DOI: 10.1002/cbic.200400210

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      Therapy with a diagnostic radionuclide?99mTc, which emits low-energy Auger electrons, induces double-strand breaks in DNA only when decaying in its direct vicinity (see structure and eletrophoresis gels). This is the first experimental evidence that this radionuclide might have potential for systemic radiotherapy, in addition to its widely known diagnostic applications.

    27. Oligosaccharide Mimics Containing Galactose and Fucose Specifically Label Tumour Cell Surfaces and Inhibit Cell Adhesion to Fibronectin (pages 422–431)

      Evelyn Y.-L. Kim, Claas Gronewold, Amitava Chatterjee, Claus-Wilhelm von der Lieth, Christian Kliem, Birgit Schmauser, Manfred Wiessler and Eva Frei

      Version of Record online: 13 JAN 2005 | DOI: 10.1002/cbic.200400092

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      Sugar substitute. Saccharide mimetics that contain biotin bind to specific areas on tumour cells (see picture). Branched structures with non-saccharide cores inhibit cell adhesion to extracellular-matrix proteins and the migration of cells through synthetic basal membranes. The most active compounds closely resemble the structure of Lewisy. The ease of their chemical synthesis allows the generation of highly diverse structures for the investigation of cell adhesion and migration.

    28. Nucleoside-Based Phospholipids and Their Liposomes Formed in Water (pages 432–439)

      Seung Kyu Choi, Tran Khac Vu, Jin Mi Jung, Su Jeong Kim, Hun Rok Jung, Taihyun Chang and Byeang Hyean Kim

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200400320

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      Tailoring vesicle properties: Synthesized nucleoside-based phospholipids (in the picture B=uracil, adenine, hypoxanthine) self-assemble into liposome-like structures in aqueous solution. TEM images (see picture background) indicate that the aggregated structures of these phospholipids are different from those of phosphatidyl nucleosides. Confocal microscopy studies indicate that complementary base pairing to oligonucleotide trimers occurs on the surface of these vesicles; this makes them attractive alternatives to glycerol- and carbohydrate-based phospholipid liposomes.

    29. From RNAi to Epigenomes: How RNA Rules The World (pages 441–443)

      Eric Westhof and Witold Filipowicz

      Version of Record online: 13 JAN 2005 | DOI: 10.1002/cbic.200400418

    30. Preview: ChemBioChem 2/2005 (page 450)

      Version of Record online: 28 JAN 2005 | DOI: 10.1002/cbic.200590006