ChemBioChem

Cover image for ChemBioChem

June 6, 2003

Volume 4, Issue 6

Pages 457–550

    1. Cover Picture: Selective Protein Degradation by Ligand-Targeted Enzymes: Towards the Creation of Catalytic Antagonists (ChemBioChem 6/2003) (page 457)

      Benjamin G. Davis, Rafael F. Sala, David R. W. Hodgson, Astrid Ullman, Kanjai Khumtaveeporn, David A. Estell, Karl Sanford, Richard R. Bott and J. Bryan Jones

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200390074

    2. Chemical Neuroimmunology: Health in a Nutshell Bidirectional Communication between Immune and Stress (Limbic-Hypothalamic-Pituitary-Adrenal) Systems (pages 466–484)

      Natalya Lozovaya and Andrew D. Miller

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200200492

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      Don't get stressed! Stress is often linked by anecdote to degeneration and disease. Key molecular, cellular and medical evidence is described in this review that gives firm support for this linkage and suggests that key stress hormones such as cortisol or corticosterone acting in synergy with the action of cytokines (see figure) may trigger and/or promote many diseases.

    3. A Molecular Mechanism of Enantiorecognition of Tertiary Alcohols by Carboxylesterases (pages 485–493)

      Erik Henke, Uwe T. Bornscheuer, Rolf D. Schmid and Jürgen Pleiss

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200200518

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      Picking the right partner: The effects of mutations on the enantioselectivity of acetylcholinesterases and a p-nitrobenzyl esterase were investigated. Experimentally determined enantioselectivities were compared to those predicted by modeling the substrate in the enzyme active site (see figure). The results indicate that there is no general rule for predicting the effects of mutations, but rather each substrate–enzyme pair must be considered separately.

    4. Synthesis, Receptor Binding, Molecular Modeling, and Proliferative Assays of a Series of 17α-Arylestradiols (pages 494–503)

      Nicolas Foy, Elie Stéphan, Anne Vessières, Emmanuel Salomon, Jan-Martin Heldt, Michel Huché and Gérard Jaouen

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200200499

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      Small changes – great potential. A series of 17α-arylestradiols (see Scheme) has been synthesized by using efficient activation methods with tetramethylethylenediamine or BF3⋅OEt2. Biochemical studies show that most of them retain good affinity for the estrogen receptors ERα and ERβ and that they act as estrogens in vitro. The possibility of easily attaching an iodo substituent to the phenyl spacer opens up a route to new radiopharmaceuticals.

    5. Synthesis of Cytidine Ribonucleotides by Stepwise Assembly of the Heterocycle on a Sugar Phosphate (pages 504–507)

      Abdul-Aziz Ingar, Richard W. A. Luke, Barry R. Hayter and John D. Sutherland

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200300554

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      Prebiotically plausible ribonucleotide synthesis: Direct attachment of cytosine to ribose to give cytidine does not occur in water. However, stepwise assembly of the base on arabinose-3-phosphate does give cytidine nucleotides (see scheme). These reactions occur readily in aqueous solutions at near-neutral pH values and it is thus plausible that they contributed to the prebiotic formation of ribonucleotides.

    6. Simplified Synthetic TMC-95A/B Analogues Retain the Potency of Proteasome Inhibitory Activity (pages 508–513)

      Zhi-Qiang Yang, Benjamin H. B. Kwok, Songnian Lin, Michael A. Koldobskiy, Craig M. Crews and Samuel J. Danishefsky

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200300560

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      Easy access: A giant step towards the development of new, more easily accessible potent proteasome inhibitors was achieved. Several simplified analogues of natural cyclic peptides TMC-95A/B were synthesized and found to retain potent proteasome inhibitory activity. The most active analogue (1) has an inhibition constant of 1.9 nM.

    7. One-Pot TiO2-Catalyzed Synthesis of Nucleic Bases and Acyclonucleosides from Formamide: Implications for the Origin of Life (pages 514–521)

      Raffaele Saladino, Umberto Ciambecchini, Claudia Crestini, Giovanna Costanzo, Rodolfo Negri and Ernesto Di Mauro

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200300567

      Where did DNA come from? Thymine, 5hydroxymethyluracil, and acyclonucleosides are synthesized in acceptable yields from formamide in the presence of TiO2. Along with the synthesis of purine, adenine, and cytosine obtained under similar conditions, these findings point to a relevant role of formamide as a precursor of nucleic acids in prebiotic conditions.

    8. Mollusk Shell Acidic Proteins: In Search of Individual Functions (pages 522–529)

      Bat-Ami Gotliv, Lia Addadi and Steve Weiner

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200200548

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      Making Minerals: Mineralized tissues such as the mollusk shell (see picture) contain an assemblage of aspartic acid rich proteins that are able to direct crystal nucleation and growth in vitro. We report a new gel-electrophoresis fixing and staining protocol for use in separating and characterizing these proteins. Our methods will allow structure to be linked to function for individual proteins involved in biomineralization.

    9. In Vivo Chaperone-Assisted Folding of α-1,6-Fucosyltransferase from Rhizobium sp. (pages 531–533)

      Agatha Bastida, Montserrat Latorre and Eduardo García-Junceda

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200200514

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      Three is not a crowd: Coexpression of the chaperonins GroEL/GroES with the α-1,6-fucosyltransferase from Rhizobium sp. allows a 10-fold increase in production of soluble and active fucosyltransferase. The His-tagged fucosyltransferase can be purified and immobilized on Ni2+-IDA-agarose gel in only one step (see Scheme). The immobilization leads to an important stabilization of the recombinant enzyme, which allows the preparation of a robust biocatalyst for the synthesis of oligosaccharides.

    10. Selective Protein Degradation by Ligand-Targeted Enzymes: Towards the Creation of Catalytic Antagonists (pages 533–537)

      Benjamin G. Davis, Rafael F. Sala, David R. W. Hodgson, Astrid Ullman, Kanjai Khumtaveeporn, David A. Estell, Karl Sanford, Richard R. Bott and J. Bryan Jones

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200300591

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      Molecular angler fish: By precisely positioning different binding ligands (L) around the active site “mouth” of a degradative proteinase enzyme, target proteins (TP) can be plucked from solution, locked in position adjacent to the catalytic triad “jaws”, and in this way readily and specifically degraded (see scheme). In this strategy, the appropriate ligand acts as a homing device to confer and enhance selectivity, in the best case by more than 350-fold, in a generic process that exploits the intrinsic, ligand-recognition capabilities of the protein target to trigger its own destruction. The hunting strategy of the deep sea Angler Fish, which uses a lure above its mouth, illustrates this principle.

    11. Binding and Catalysis: A Thermodynamic Study on a Catalytic Antibody System (pages 537–540)

      Herschel Wade and Thomas S. Scanlan

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200300563

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      Binding versus catalysis: Attempts to obtain efficient catalysts by using conventional screening methods raise a question concerning the connection between binding and catalysis. To address this issue, we have determined the thermodynamic parameters for the binding of several phosphonates to the esterolytic antibody 17E8 (see scheme). Our results suggest that there may be thermodynamic differences between a binding site selected from a screen for tight transition-state-analogue binding and one that is designed for efficient catalysis.

    12. Preview: ChemBioChem 6/2003 (page 550)

      Version of Record online: 2 JUN 2003 | DOI: 10.1002/cbic.200390082

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