ChemBioChem

Cover image for Vol. 13 Issue 17

November 26, 2012

Volume 13, Issue 17

Pages 2461–2621

  1. Cover Pictures

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
    1. You have free access to this content
      Cover Picture: Identification of the Verruculogen Prenyltransferase FtmPT3 by a Combination of Chemical, Bioinformatic and Biochemical Approaches (ChemBioChem 17/2012) (page 2461)

      Kathrin Mundt, Beate Wollinsky, Prof. Dr. Han-Li Ruan, Assoc. Prof. Dr. Tianjiao Zhu and Prof. Dr. Shu-Ming Li

      Version of Record online: 17 NOV 2012 | DOI: 10.1002/cbic.201290070

      Thumbnail image of graphical abstract

      The cover picture shows a successful strategy to identify secondary-metabolite biosynthetic genes by a combination of chemical, bioinformatics, and biochemical approaches. After isolation and identification of several metabolites of the fumitremorgin-type alkaloids, especially of fumitremorgin A, from cultures of the ascomycetous fungus Neosartorya fischeri NRRL181, S.-M. Li et al. identified a putative prenyltransferase gene ftmPT3 in its genome sequence. Biochemical investigation of the recombinant FtmPT3 proved its role in the conversion of verruculogen to fumitremorgin A. Comparison of the genome sequence of N. fischeri with that of its close relative Aspergillus fumigatus revealed that both fungi contain genes for the biosynthesis of verruculogen and that ftmPT3 is located on a different fragment in N. fischeri than in the identified verruculogen cluster. No homologue gene was identified in the genome sequences of A. fumigatus strains, thus providing evidence for the accumulation of verruculogen as the end product of the biosynthetic pathway of fumitremorgin-type alkaloids in A. fumigatus. See p. 2583 ff. for more details.

    2. You have free access to this content
      Inside Cover: A Peptide Photoaffinity Probe Specific for the Active Conformation of the Abl Tyrosine Kinase (ChemBioChem 17/2012) (page 2462)

      Dr. Yang Deng, Dr. Brian A. Couch, Prof. Anthony J. Koleske and Prof. Benjamin E. Turk

      Version of Record online: 17 NOV 2012 | DOI: 10.1002/cbic.201290071

      Thumbnail image of graphical abstract

      The inside cover picture shows a peptide photoaffinity label modeled into the active site of the Abl tyrosine kinase. On p. 2510 ff., B. E. Turk et al. show that probes based on Abl substrates label only the active conformation of the kinase. These probes can be used to monitor Abl in complex mixtures and to decipher the mechanisms of action of small-molecule Abl inhibitors.

  2. Graphical Abstract

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
  3. News

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
  4. Review

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
    1. Synthesis of Glycopolymers by Controlled Radical Polymerization Techniques and Their Applications (pages 2478–2487)

      Dr. Vimary Vázquez-Dorbatt, Juneyoung Lee, En-Wei Lin and Prof. Heather D. Maynard

      Version of Record online: 6 NOV 2012 | DOI: 10.1002/cbic.201200480

      Thumbnail image of graphical abstract

      Sugar mimics: Glycopolymers, polymers with pendent saccharide groups, are studied as potential natural saccharide mimics. Controlled radical polymerization techniques have facilitated the synthesis, characterization, and conjugation of glycopolymers. This review discusses the synthesis of and several applications of the glycopolymers made by these techniques.

  5. Communications

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
    1. A Bioorthogonal Chemoenzymatic Strategy for Defined Protein Dendrimer Assembly (pages 2489–2494)

      Kanchan Gupta, Shikha Singh, Kallol Gupta, Naeem Khan, Dr. Devinder Sehgal, Dr. V. Haridas and Dr. Rajendra P. Roy

      Version of Record online: 5 OCT 2012 | DOI: 10.1002/cbic.201200559

      Thumbnail image of graphical abstract

      Protein dendrimers made easy: We present a chemoenzymatic strategy for the synthesis of well-defined protein dendrimers in which proteins orthogonally labelled by sortase-mediated ligation are conjugated to a dendritic scaffold by azide–alkyne cycloaddition. This “sortase-click” strategy uses readily accessible His6-tagged proteins and can serve as a powerful method for the covalent assembly of multivalent proteins.

    2. Coupling Reaction of Indolepyruvic Acid by StaD and Its Product: Implications for Biosynthesis of Indolocarbazole and Violacein (pages 2495–2500)

      Dr. Shumpei Asamizu, Dr. Satoshi Hirano, Prof. Hiroyasu Onaka, Dr. Hiroyuki Koshino, Dr. Yoshitsugu Shiro and Prof. Shingo Nagano

      Version of Record online: 18 OCT 2012 | DOI: 10.1002/cbic.201200535

      Thumbnail image of graphical abstract

      Central C[BOND]C coupling: It has been proposed that the heme-containing enzyme StaD and its homologues catalyze a coupling reaction that yields an indolepyruvic acid (IPA) imine in indolocarbazole biosynthesis. We show that StaD uses IPA enol as an analogue of natural substrate to produce an IPA dimer, in the first direct evidence of the C[BOND]C coupling dimerization reaction catalyzed by StaD.

    3. A Single-Cell NMR Membrane Transport Assay (pages 2501–2504)

      Prof. Dr. Werner Kremer, Prof. Dr. Hans Robert Kalbitzer, Dr. Christina Schreier, Dr. Fritz Huber, Christine Schulze, Prof. Dr. Hannelore Daniel and Dr. Jürgen Stolz

      Version of Record online: 23 OCT 2012 | DOI: 10.1002/cbic.201200514

      Thumbnail image of graphical abstract

      Peptide transport: We describe a generally applicable NMR-based assay that can detect transport processes across the plasma membrane on a single-cell level. Single-cell 1D 1H NMR spectroscopy clearly demonstrated the presence of transported substrates inside the cells. NMR-based measurements involving single cRNA-injected oocytes might provide an ab initio method for searching for transported substrates.

    4. Investigating the Binding Mode of an Inhibitor of the MBNL1⋅RNA Complex in Myotonic Dystrophy Type 1 (DM1) Leads to the Unexpected Discovery of a DNA-Selective Binder (pages 2505–2509)

      Chun-Ho Wong, Dr. Stacie L. Richardson, Yen-Jun Ho, Alex M. H. Lucas, Prof. Dr. Tiziano Tuccinardi, Prof. Dr. Anne M. Baranger and Prof. Dr. Steven C. Zimmerman

      Version of Record online: 24 OCT 2012 | DOI: 10.1002/cbic.201200602

      Thumbnail image of graphical abstract

      Recognition made easy: The selectivity of a small-molecule inhibitor that binds CTG and CUG sites with similar affinity can be shifted toward exclusive CTG recognition by a single N-methylation. Biophysical studies and MD simulations provide insights into the DNA and RNA recognition.

    5. A Peptide Photoaffinity Probe Specific for the Active Conformation of the Abl Tyrosine Kinase (pages 2510–2512)

      Dr. Yang Deng, Dr. Brian A. Couch, Prof. Anthony J. Koleske and Prof. Benjamin E. Turk

      Version of Record online: 18 OCT 2012 | DOI: 10.1002/cbic.201200560

      Thumbnail image of graphical abstract

      An Abl label: The design of sensors to monitor the activity state of specific protein kinases is challenging due to the complexity of eukaryotic kinomes. Here we describe a peptide-based photoaffinity probe that specifically labels the active conformation of the Abl tyrosine kinase.

    6. Amido-Bridged Nucleic Acids (AmNAs): Synthesis, Duplex Stability, Nuclease Resistance, and in Vitro Antisense Potency (pages 2513–2516)

      Aiko Yahara, Dr. Ajaya Ram Shrestha, Dr. Tsuyoshi Yamamoto, Dr. Yoshiyuki Hari, Takashi Osawa, Masaki Yamaguchi, Dr. Masaru Nishida, Dr. Tetsuya Kodama and Prof. Dr. Satoshi Obika

      Version of Record online: 18 OCT 2012 | DOI: 10.1002/cbic.201200506

      Thumbnail image of graphical abstract

      Towards the next generation: New LNA analogues based on a cyclic amide structure, termed amido-bridged nucleic acids (AmNAs), have been synthesized. Oligonucleotides modified with these residues showed high nuclease resistance along with high binding affinities towards complementary strands.

    7. Inhibition of Guanosine Monophosphate Synthetase by the Substrate Enantiomer L-XMP (pages 2517–2520)

      Nicholas B. Struntz, Dr. Tianshun Hu, Dr. Brian R. White, Margaret E. Olson and Prof. Dr. Daniel A. Harki

      Version of Record online: 23 OCT 2012 | DOI: 10.1002/cbic.201200503

      Thumbnail image of graphical abstract

      Mirror, mirror…? The enantioselectivity of guanosine monophosphate synthetase (GMPS), a key enzyme in GMP biosynthesis, was characterized by using D- and L-xanthosine 5′-monophosphate (XMP) as substrates. L-XMP was found to be converted to L-GMP by E. coli GMPS and to inhibit enzymatic activity. These results provide insight into GMPS–ligand interactions that might be useful in future inhibitor design.

  6. Full Papers

    1. Top of page
    2. Cover Pictures
    3. Graphical Abstract
    4. News
    5. Review
    6. Communications
    7. Full Papers
    1. A Backup Plan for Self-Protection: S-Methylation of Holomycin Biosynthetic Intermediates in Streptomyces clavuligerus (pages 2521–2526)

      Dr. Bo Li, Ry R. Forseth, Prof. Dr. Albert A. Bowers, Prof. Dr. Frank C. Schroeder and Prof. Dr. Christopher T. Walsh

      Version of Record online: 24 OCT 2012 | DOI: 10.1002/cbic.201200536

      Thumbnail image of graphical abstract

      A good host looks after itself! The redox accessibility of the cyclic disulfide in holomycin is likely essential to its biological activity. We used metabolite profiling of genetic deletion mutants (ΔhlmI) incapable of disulfide formation to identify a number of shunt products. In these newly identified compounds, the enethiol warheads have been incapacitated by a combination of S-methylation and dimerization as a host strategy for self-protection.

    2. Type II Ligands as Chemical Auxiliaries To Favor Enzymatic Transformations by P450 2E1 (pages 2527–2536)

      Amélie Ménard, Camilo Fabra, Yue Huang and Prof. Karine Auclair

      Version of Record online: 5 NOV 2012 | DOI: 10.1002/cbic.201200524

      Thumbnail image of graphical abstract

      Controlling P450 transformations: Type II ligands contain an aromatic nitrogen that coordinates to the heme iron in the active site of cytochrome P450 enzymes. The type II ligand nicotinate can serve as a useful chemical auxiliary for biocatalysis with P450 2E1 by promoting the predictable oxidation of small hydrocarbon substrates.

    3. Total Synthesis of (−)-Doliculide, Structure–Activity Relationship Studies and Its Binding to F-Actin (pages 2537–2548)

      Dr. Kiran Matcha, Dr. Ashoka V. R. Madduri, Dr. Sayantani Roy, Dr. Slava Ziegler, Prof. Dr. Herbert Waldmann, Dr. Anna K. H. Hirsch and Prof. Dr. Adriaan J. Minnaard

      Version of Record online: 5 NOV 2012 | DOI: 10.1002/cbic.201200512

      Thumbnail image of graphical abstract

      Actin' on cancers: An efficient catalytic, asymmetric synthesis of (−)-doliculide (shown in yellow) is reported. Its effect, and that of its analogues, was tested with two cancer cell lines. Its binding mode to F-actin was modeled and shown to be similar to that of jasplakinolide and chondramide C (gray).

    4. Two Synthetic Antibodies that Recognize and Neutralize Distinct Proteolytic Forms of the Ebola Virus Envelope Glycoprotein (pages 2549–2557)

      Jayne F. Koellhoffer, Dr. Gang Chen, Rohini G. Sandesara, Dr. Shridhar Bale, Prof. Dr. Erica Ollmann Saphire, Prof. Dr. Kartik Chandran, Prof. Dr. Sachdev S. Sidhu and Prof. Dr. Jonathan R. Lai

      Version of Record online: 30 OCT 2012 | DOI: 10.1002/cbic.201200493

      Thumbnail image of graphical abstract

      A tale of two antibodies: Ebola virus (EBOV) causes severe hemorrhagic fever associated with high mortality rates. Here we report the identification of two synthetic antibody fragments that have orthogonal binding and neutralization profiles against two prefusion forms of the EBOV glycoprotein. These antibodies provide new tools for dissecting intermediates of viral membrane fusion and entry. (56 words)

    5. Residue 75 of Interleukin-8 is Crucial for its Interactions with Glycosaminoglycans (pages 2558–2566)

      Karoline Nordsieck, Annelie Pichert, Dr. Sergey A. Samsonov, Dr. Lars Thomas, Dr. Christian Berger, Dr. M. Teresa Pisabarro, Prof. Dr. Daniel Huster and Prof. Dr. Annette G. Beck-Sickinger

      Version of Record online: 15 OCT 2012 | DOI: 10.1002/cbic.201200467

      Thumbnail image of graphical abstract

      Protein–GAG interactions: Residue 75 of interleukin-8 (IL-8) plays a major role in the interactions between IL-8 and glycosaminoglycans (GAGs). Here, investigation of a selectively 15N-labeled E75K IL-8 variant by spectroscopic techniques and molecular docking has shown the importance of amino acids 34 to 36 for the interaction with GAGs for the first time.

    6. Tailoring Encodable Lanthanide-Binding Tags as MRI Contrast Agents (pages 2567–2574)

      Dr. Kelly D. Daughtry, Dr. Langdon J. Martin, Ashish Sarraju, Prof. Barbara Imperiali and Prof. Karen N. Allen

      Version of Record online: 13 NOV 2012 | DOI: 10.1002/cbic.201200448

      Thumbnail image of graphical abstract

      The ins and outs of water: Seventeen-residue lanthanide-binding tags (LBTs) have been used as a template for developing gadolinium-binding tags that exhibit enhanced contrast for MRI. The MRI-LBT sequence was further optimized as a coexpression tag on a model protein, ultimately affording a prototype peptide-based MRI agent.

    7. Structure-Based Mutational Study of an Archaeal DNA Ligase towards Improvement of Ligation Activity (pages 2575–2582)

      Maiko Tanabe, Dr. Sonoko Ishino, Prof. Masafumi Yohda, Prof. Kosuke Morikawa, Prof. Yoshizumi Ishino and Dr. Hirokazu Nishida

      Version of Record online: 6 NOV 2012 | DOI: 10.1002/cbic.201200336

      Thumbnail image of graphical abstract

      Super mutant: We report a series of mutations in the domain boundary of Pyrococcus furiosus DNA ligase, and demonstrate that the replacement of Asp540 with a positively charged residue improved the ligation activity. The increased activity of the Asp540 mutant is attributed to efficient adenylylation and DNA binding.

    8. Identification of the Verruculogen Prenyltransferase FtmPT3 by a Combination of Chemical, Bioinformatic and Biochemical Approaches (pages 2583–2592)

      Kathrin Mundt, Beate Wollinsky, Prof. Dr. Han-Li Ruan, Assoc. Prof. Dr. Tianjiao Zhu and Prof. Dr. Shu-Ming Li

      Version of Record online: 26 OCT 2012 | DOI: 10.1002/cbic.201200523

      Thumbnail image of graphical abstract

      Spectacular identification: Conversion of verruculogen to fumitremorgin A was demonstrated biochemically with a recombinant O-prenyltransferase, FtmPT3. The responsible gene was not located within the previously identified fumitremorgin gene cluster in N. fischeri NRRL181.

    9. Flavin Conjugates for Delivery of Peptide Nucleic Acids (pages 2593–2598)

      Dr. Fanny Marlin, Dr. Philippe Simon, Dr. Stéphanie Bonneau, Dr. Patrizia Alberti, Céline Cordier, Charlotte Boix, Loïc Perrouault, Aurélie Fossey, Prof. Tula Saison-Behmoaras, Prof. Marc Fontecave and Dr. Carine Giovannangeli

      Version of Record online: 5 NOV 2012 | DOI: 10.1002/cbic.201200505

      Thumbnail image of graphical abstract

      Travel pass: PNAs are promising molecules for artificial regulation of gene expression and we report here that the conjugation of flavins to PNAs is a novel way to obtain functional antisense PNAs.

    10. Dimethylarginine-Dimethylaminohydrolase-2 (DDAH-2) Does Not Metabolize Methylarginines (pages 2599–2604)

      Karin S. Altmann, Dr. Antje Havemeyer, Prof. Dr. Eric Beitz and Prof. Dr. Bernd Clement

      Version of Record online: 4 NOV 2012 | DOI: 10.1002/cbic.201200499

      Thumbnail image of graphical abstract

      Physiological regulation of NO metabolism: Investigations into the methylarginine metabolism of DDAH-2 should yield evidence of isoform selectivity for DDAH-1 inhibitors. In contrast to DDAH-1, no metabolism of the postulated substrates L-NMMA or ADMA was observed for DDAH-2. Therefore, this reaction is not suitable to detect the influence of DDAH-1 inhibitors on DDAH-2 activity.

    11. Chemical Synthesis and Enzymatic Testing of CMP-Sialic Acid Derivatives (pages 2605–2615)

      Dr. Saskia Wolf, Dr. Svenja Warnecke, Jörg Ehrit, Dr. Friedrich Freiberger, Prof. Dr. Rita Gerardy-Schahn and Prof. Dr. Chris Meier

      Version of Record online: 5 NOV 2012 | DOI: 10.1002/cbic.201200471

      Thumbnail image of graphical abstract

      Sialic acid modification: CycloSal-nucleotides were used to prepare monophosphate-linked sugar nucleotides, such as TMP-β-Gal and CMP–N-acetyl-neuraminic acids and four sialic acid derivatives with different modifications at their amino functions. The CMP–sialic acid derivatives were studied in a polymerisation catalysed by a bacterial polysialyltransferase.

    12. A Novel Photoaffinity-Based Probe for Selective Detection of Cathepsin L Active Form (pages 2616–2621)

      Ana Torkar, Dr. Sarah Bregant, Dr. Laurent Devel, Dr. Marko Novinec, Dr. Brigita Lenarčič, Dr. Tamara Lah and Dr. Vincent Dive

      Version of Record online: 4 NOV 2012 | DOI: 10.1002/cbic.201200389

      Thumbnail image of graphical abstract

      CatL catcher: A photoaffinity probe incorporating a photoactivatable benzophenone group was shown to label the active form of cathepsin L selectively in the presence of a set of recombinant cathepsins and cell-extracted proteins. This probe should be of value for detecting the secreted active form of cathepsin L from in vitro or ex vivo samples.

SEARCH

SEARCH BY CITATION