ChemBioChem

Cover image for ChemBioChem

September 22, 2008

Volume 9, Issue 14

Pages 2169–2338

  1. Cover Picture

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireview
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Review
    10. Preview
    1. Cover Picture: Studies of the Structure of the N-Terminal Domain from the Y4 Receptor—a G Protein-Coupled Receptor—and its Interaction with Hormones from the NPY Family (ChemBioChem 14/2008) (page 2169)

      Chao Zou, Sowmini Kumaran, Stefan Markovic , Reto Walser and Oliver Zerbe

      Version of Record online: 23 SEP 2008 | DOI: 10.1002/cbic.200890053

      Thumbnail image of graphical abstract

      The cover picture shows the conformation of a structured region of the N-terminal domain of the Y4 receptor, a mammalian GPCR, as determined in this issue. The remainder of the receptor and its ligand, the pancreatic polypeptide, is drawn schematically. Signaling through the Y4 receptor influences important physiological functions such as gastrointestinal regulation. The extracellular domain of the Y4 receptor was expressed, and NMR techniques revealed it to be mostly flexible with the exception of a membrane-associated helix. The pancreatic polypeptide (PP) binds to the N-terminal domain with a dissociation constant of ∼50 mM as measured by surface-plasmon resonance; while site-directed mutagenesis revealed that electrostatic interactions dominate. In contrast, neuropeptide Y (NPY) and the peptide YY (PPY), which target this receptor subtype with lower affinity, also bind significantly less strongly to the N-terminal domain of Y4. For further details see the article by O. Zerbe et al. on p. 2276 ff.

  2. Graphical Abstract

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

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

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireview
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Review
    10. Preview
    1. Achieving Turnover in DNA-Templated Reactions (pages 2185–2192)

      Tom N. Grossmann, Anne Strohbach and Oliver Seitz

      Version of Record online: 27 AUG 2008 | DOI: 10.1002/cbic.200800290

      Thumbnail image of graphical abstract

      Quasi-intramolecular: Templates bind reactants and increase the effective molarity of their reactive groups. This results in the acceleration of the templated reactions. Programmable self-recognition properties make nucleic acids particularly well adapted to templated synthesis, and have resulted in applications in DNA and RNA detection, prodrug activation and asymmetric catalysis. This minireview aims to summarise the current state of templated reactions catalysed by DNA and RNA.

  5. Highlight

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireview
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Review
    10. Preview
    1. Putting the Pieces Together: Histone H2B Ubiquitylation Directly Stimulates Histone H3K79 Methylation (pages 2193–2195)

      Albert Jeltsch and Philipp Rathert

      Version of Record online: 19 AUG 2008 | DOI: 10.1002/cbic.200800414

      Thumbnail image of graphical abstract

      Cause and effect: McGinty et al. (2008) have semisynthetically prepared a nucleosome ubiquitylated at H2K120 to show that the Dot1 histone methyltransferase is directly stimulated by H2B ubiquitylation.

  6. Communications

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireview
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Review
    10. Preview
    1. Glycomimetic Inhibitors of Mycobacterial Glycosyltransferases: Targeting the TB Cell Wall (pages 2197–2199)

      Ricardo Lucas, Patricia Balbuena, James C. Errey, Marie A. Squire, Sudagar S. Gurcha, Michael McNeil, Gurdyal S. Besra and Benjamin G. Davis

      Version of Record online: 9 SEP 2008 | DOI: 10.1002/cbic.200800189

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      Tear down the wall: Ready methods for the construction of libraries of both α- and β-aza-C-rhamnomimetics with high levels of diastereoselectivity have allowed the identification of inhibitors of rhamnosyl-processing enzymes. These include the first examples of analogues of the Mycobacterium tuberculosis sugar L-rhamnose that are inhibitors of mycobacterial biosynthetic pathways.

    2. N-Methyl Scanning Mutagenesis Generates Protease-Resistant G Protein Ligands with Improved Affinity and Selectivity (pages 2200–2203)

      Stephen V. Fiacco and Richard W. Roberts

      Version of Record online: 9 SEP 2008 | DOI: 10.1002/cbic.200800208

      Scanning for bioavailability: N-methyl incorporation does not have to be at the scissile bond to dramatically enhance protease resistance. N-methyl scanning around the scissile bond has yielded compounds that are also more selective and bind with higher affinity.

    3. A Novel Label-Free Biosensor Using an Aptazyme–Suppressor-tRNA Conjugate and an Amber Mutated Reporter Gene (pages 2204–2208)

      Atsushi Ogawa and Mizuo Maeda

      Version of Record online: 29 AUG 2008 | DOI: 10.1002/cbic.200800294

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      Freedom of expression: A theophylline-dependent aptazyme was tethered to the 5′ terminus of the anticodon-adjusted suppressor tRNASerUCUA (aptazyme–suppressor-tRNA conjugates; AST) and the AST was combined with an amber-mutated luciferase gene in a prokaryotic cell-free translation system to construct AST biosensors (see scheme).

    4. Investigation into the Mechanism of Phenolic Couplings during the Biosynthesis of Glycopeptide Antibiotics (pages 2209–2214)

      Andrew N. Holding and Jonathan B. Spencer 

      Version of Record online: 1 AUG 2008 | DOI: 10.1002/cbic.200800303

      Thumbnail image of graphical abstract

      Three haem-containing P450 enzymes catalyse the phenolic cross links that occur during the biosynthesis of vancomycin-like glycopeptides. By isotopically labelling amino acids within the peptide backbone, the mechanism of all three of these enzymes can be probed.

    5. S-Adenosyl-L-Methionine Hydrolase (Adenosine-Forming), a Conserved Bacterial and Archeal Protein Related to SAM-Dependent Halogenases (pages 2215–2219)

      Alessandra S. Eustáquio, Johannes Härle, Joseph P. Noel and Bradley S. Moore

      Version of Record online: 21 AUG 2008 | DOI: 10.1002/cbic.200800341

      Thumbnail image of graphical abstract

      Halogenase versus hydrolase: The newly discovered SAM-dependent halogenases belong to a family of over 100 proteins from bacteria and archaea. Biochemical and in silico analyses reported here suggest, however, that most of these relatives act as previously unknown SAM adenosylhydrolases rather than halogenases.

    6. Live-Cell Fluorescence Microscopy of Directed Cell Migration on Partially Etched Electroactive SAM Gold Surfaces (pages 2220–2224)

      Brian M. Lamb, Nathan P. Westcott and Muhammad N. Yousaf

      Version of Record online: 27 AUG 2008 | DOI: 10.1002/cbic.200800400

      Thumbnail image of graphical abstract

      We combine three new straightforward technologies (summarized in the figure) to obtain complete spatial and visual control of directed cell polarity and migration. We also use a chemoselective, electroactive immobilization strategy to pattern ligands onto partially etched gold surfaces, which are compatible with live cell fluorescence microscopy, and demonstrate the utility of this technique for tracking directed cell migration.

    7. Saturation Transfer Difference (STD) NMR Spectroscopy Characterization of Dual Binding Mode of a Mannose Disaccharide to DC-SIGN (pages 2225–2227)

      Jesús Angulo, Irene Díaz, José J. Reina, Georges Tabarani, Franck Fieschi, Javier Rojo and Pedro M. Nieto

      Version of Record online: 21 AUG 2008 | DOI: 10.1002/cbic.200800361

      Thumbnail image of graphical abstract

      Concurrent multiple binding modes of a single ligand can be detected and quantified by saturation transfer difference (STD) NMR spectroscopy. Analysis of experimental and predicted STD initial growing rates has allowed us to determine the precise orientation of Man α(1[RIGHTWARDS ARROW]2)Man in the minor complex with the carbohydrate recognition domain of DC-SIGN.

  7. Full Papers

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireview
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Review
    10. Preview
    1. Chemical Genetic Analysis of FOXO Nuclear–Cytoplasmic Shuttling by Using Image-Based Cell Screening (pages 2229–2237)

      Fabian Zanella, Aranzazú Rosado, Beatriz García, Amancio Carnero and Wolfgang Link

      Version of Record online: 29 AUG 2008 | DOI: 10.1002/cbic.200800255

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      Localizing FOXO: The subcellular localization of FOXO proteins plays a major role in the regulation of their activity. In cancer research, the regulation of FOXO factors is receiving increasing attention as their activation has been linked to cell-cycle arrest and apoptosis. Hence, FOXO proteins have been proposed to act as tumor suppressors. Heren, we report a chemical biology approach to studying the mechanisms that influence their intracellular localization.

    2. Molecular Evolution of a Defined DNA Sequence with Accumulation of Mutations in a Single Round by a Dual Approach to Random Chemical Mutagenesis (DuARCheM) (pages 2238–2243)

      Utpal Mohan and Uttam Chand Banerjee

      Version of Record online: 29 AUG 2008 | DOI: 10.1002/cbic.200800259

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      Dual Approach to Random Chemical Mutagenesis (DuARCheM) could help to change the face of random chemical mutagenesis because the combination of both in vivo and in vitro approaches mimics the amplification and mutation that is carried out by a PCR-based mutagenesis system, and at the same time the mutations are confined to the desired gene.

    3. Screening the Structural and Functional Properties of Bicyclo-DNA: bcox-DNA (pages 2244–2253)

      Samuel Luisier and Christian J. Leumann

      Version of Record online: 29 AUG 2008 | DOI: 10.1002/cbic.200800322

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      Adjusting nucleic acid conformations: A novel carbohydrate-modified bicyclo-DNA nucleoside carrying a lipophilic benzyloxime substituent on the carbocyclic ring was synthesized and incorporated into DNA. It destabilizes DNA but can stabilize RNA duplexes. While no cellular uptake of the modified oligonucleotides into HeLa cells occurred in the absence of transfecting agents, improved cellular uptake properties were observed when they were complexed to lipofectamine.

    4. Comparison of Design Strategies for Promotion of β-Peptide 14-Helix Stability in Water (pages 2254–2259)

      Esther Vaz, William C. Pomerantz, Matthias Geyer, Samuel H. Gellman and Luc Brunsveld

      Version of Record online: 29 AUG 2008 | DOI: 10.1002/cbic.200800355

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      Stable foldamer conformations: Direct comparison of three distinct strategies designed to stabilize the 14-helix secondary structure in short β-peptides showed that either a covalent bridge or the incorporation of cyclic ACHC residues generated a stable helix in water. The ACHC residues generate a highly ordered backbone, whereas cyclization results in high order in the side chains.

    5. Constructing and Analyzing the Fitness Landscape of an Experimental Evolutionary Process (pages 2260–2267)

      Manfred T. Reetz and Joaquin Sanchis

      Version of Record online: 19 AUG 2008 | DOI: 10.1002/cbic.200800371

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      An inside view: Iterative saturation mutagenesis, which was used to enhance the enantioselectivity of an enzyme in five steps, has been illuminated by constructing the 5!=120 pathways leading from the wild-type to the final mutant. This type of analysis can be used to assess mutagenesis methods in directed evolution.

    6. But-3-ene-1,2-diol: A Mechanism-Based Active Site Inhibitor for Coenzyme B12-Dependent Glycerol Dehydratase (pages 2268–2275)

      Antonio J. Pierik, Torsten Graf, Louise Pemberton, Bernard T. Golding and János Rétey

      Version of Record online: 2 SEP 2008 | DOI: 10.1002/cbic.200800213

      Thumbnail image of graphical abstract

      Coenzyme B12-dependent glycerol dehydratase is a radical enzyme that catalyses the conversion of glycerol into 3-hydroxypropanal and propane-1,2-diol into propanal. The glycerol dehydratases are of industrial interest because they offer a biotechnological route to propane-1,3-diol, a building block for polymers. In this paper we present a study of the behaviour of but-3-ene-1,2-diol and specifically labelled (2H, 14C) analogues with a recombinant glycerol dehydratase.

    7. Studies of the Structure of the N-Terminal Domain from the Y4 Receptor—a G Protein-Coupled Receptor—and its Interaction with Hormones from the NPY Family (pages 2276–2284)

      Chao Zou, Sowmini Kumaran, Stefan Markovic , Reto Walser and Oliver Zerbe

      Version of Record online: 2 SEP 2008 | DOI: 10.1002/cbic.200800221

      Thumbnail image of graphical abstract

      Helices and membranes: The N-terminal domain from the human Y4 receptor, a GPCR mainly targeted by the pancreatic polypeptide, was synthesized in a recombinant fashion. The solution structure was determined by NMR in the presence of phospholipid micelles, and its interactions with peptides from the NPY family were tested by NMR and SPR techniques.

    8. Eyes Absent Proteins: Characterization of Substrate Specificity and Phosphatase Activity of Mutants Associated with Branchial, Otic and Renal Anomalies (pages 2285–2294)

      Amna Musharraf, Nicole Markschies, Kathleen Teichmann, Susann Pankratz, Kathrin Landgraf, Christoph Englert and Diana Imhof

      Version of Record online: 29 AUG 2008 | DOI: 10.1002/cbic.200800224

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      Eyes absent (Eya) proteins that function as transcriptional coactivators with an intrinsic phosphatase activity were previously recognised as being phosphotyrosine specific. Here, we demonstrate that both aryl and acyl phosphates are efficient substrates of plant and human Eya proteins. Thus, in addition to pY proteins, small physiologically relevant molecules might be substrates of Eya proteins in vivo.

    9. Generation of New Derivatives of the Antitumor Antibiotic Mithramycin by Altering the Glycosylation Pattern through Combinatorial Biosynthesis (pages 2295–2304)

      María Pérez, Irfan Baig, Alfredo F. Braña, José A. Salas, Jürgen Rohr and Carmen Méndez

      Version of Record online: 29 AUG 2008 | DOI: 10.1002/cbic.200800299

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      Sugar profile modification: By using a combinatorial biosynthesis approach, nine mithramycin derivatives were generated with alterations in the glycosylation pattern. The wild-type S. argillaceus strain and the S. argillaceus M7U1 strain were used as hosts to express various “sugar plasmids” each directing the biosynthesis of a different deoxyhexose. All compounds showed antitumor activity against different tumor cell lines.

    10. DNA with Branched Internal Side Chains: Synthesis of 5-Tripropargylamine-dU and Conjugation by an Azide-Alkyne Double Click Reaction (pages 2305–2316)

      Venkata Ramana Sirivolu, Padmaja Chittepu and Frank Seela

      Version of Record online: 9 SEP 2008 | DOI: 10.1002/cbic.200800313

      Thumbnail image of graphical abstract

      Branching in: 5-Tripropargylamine-2′-deoxyuridine was synthesized and incorporated into oligonucleotides. The two terminal triple bonds were functionalized with different azido reporter groups (AZT, 3-azido-7-hydroxycoumarin) by means of copper(I)-mediated 1,3-dipolar cycloadditions. Such methodology allows the simultaneous post-modification of DNA by two reporter molecules and can be applied to almost any azido derivatives (proteins, carbohydrates, lipids etc.) including those capable of forming dendrimeric structures.

    11. Site-Specific Chemical Modification of Proteins with a Prelabelled Cysteine Tag Using the Artificially Split Mxe GyrA Intein (pages 2317–2325)

      Thomas Kurpiers and Henning D. Mootz

      Version of Record online: 29 AUG 2008 | DOI: 10.1002/cbic.200800319

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      It takes two (pieces): The selective chemical modification of a protein can be achieved through assembly of the protein from two parts by using protein trans-splicing. We report the generation of the artificially split Mxe GyrA intein and show its superior performance in attaching a prelabelled cysteine tag to a protein of interest.

    12. Synthesis and Biological Characterisation of Targeted Pro-Apoptotic Peptide (pages 2326–2332)

      Stéphanie Foillard, Zhao-hui Jin, Elisabeth Garanger, Didier Boturyn, Marie-Christine Favrot, Jean-Luc Coll and Pascal Dumy

      Version of Record online: 19 AUG 2008 | DOI: 10.1002/cbic.200800327

      Thumbnail image of graphical abstract

      Drug-delivery system: A sophisticated compound comprised of two functional domains, one a tumour “homing” motif and the other an apoptosis-inducing peptide, was prepared through a combination of solid- and solution-phase techniques. Biological studies showed that a multivalent RGD-containing compound bearing the pro-apoptotic KLA moiety triggers apoptosis and cell death in a αVβ3 integrin-expressing cell line. This offers an interesting outlook for tumour-targeted drug delivery.

  8. Book Review

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

    1. Top of page
    2. Cover Picture
    3. Graphical Abstract
    4. News
    5. Minireview
    6. Highlight
    7. Communications
    8. Full Papers
    9. Book Review
    10. Preview
    1. Preview: ChemBioChem 15/2008 (page 2338)

      Version of Record online: 23 SEP 2008 | DOI: 10.1002/cbic.200890056

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