Cover image for ChemBioChem

March 3, 2003

Volume 4, Issue 2-3

Pages 125–238

    1. Cover Picture: NMR Structure of the Single QALGGH Zinc Finger Domain from the Arabidopsis thaliana SUPERMAN Protein (ChemBioChem 2-3/2003) (page 125)

      Carla Isernia, Enrico Bucci, Marilisa Leone, Laura Zaccaro, Paola Di Lello, Giuseppe Digilio, Sabrina Esposito, Michele Saviano, Benedetto Di Blasio, Carlo Pedone, Paolo V. Pedone and Roberto Fattorusso

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390021

    2. Graphical Abstract: ChemBioChem 2-3/2003 (pages 127–132)

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390022

    3. Kurt Wüthrich, the ETH Zürich, and the Development of NMR Spectroscopy for the Investigation of Structure, Dynamics, and Folding of Proteins (pages 135–142)

      Harald Schwalbe

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390023

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      Spinning to the top: In 2002, the Nobel prize committee awarded one half of the Nobel prize in Chemistry to Prof. Kurt Wüthrich, of the Eidgenössische Technische Hochschule Zürich, “for his development of nuclear magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in solution.” This Minireview summarizes Wüthrich's scientific contributions to this field and tells the story of the development of NMR spectroscopy for the study of biological macromolecules in general and of proteins (see picture) in particular.

    4. Modulated Nucleoside Kinases as Tools to Improve the Activation of Therapeutic Nucleoside Analogues (pages 143–146)

      Christian Monnerjahn and Manfred Konrad

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390024

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      Improving traditional chemotherapy: Rate-limiting enzymes of the intracellular activation of nucleoside analogue prodrugs, such as the herpes simplex virus thymidine kinase for the antiherpes compound GCV (see picture), can be modified to more active and specific prodrug activators by using structure-derived site-specific mutagenesis. Such prodrug/designed enzyme systems hold enormous promise in gene therapy strategies for the treatment of cancer and viral infections.

    5. Polyglycine II Nanosheets: Supramolecular Antivirals? (pages 147–154)

      Alexander B. Tuzikov, Alexander A. Chinarev, Alexandra S. Gambaryan, Vladimir A. Oleinikov, Dmitry V. Klinov, Nadezhda B. Matsko, Vasily A. Kadykov, Mikhail A. Ermishov, Il'ya V. Demin, Victor V. Demin, Phil D. Rye and Nicolai V. Bovin

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390025

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      Wrapping up against a cold: Self-assembly of tetraantennary peptides [glycinen-NHCH2]4C through intermolecular hydrogen bonding leads to the formation of stable noncovalent polyglycine-II-type structures in water. These submicron-sized structures consist of one-molecule-thick flat sheets (see figure). The attachment of α-N-acetylneuraminic acid to the terminal glycine residues gives rise to water-soluble self-assembled glycopeptide sheets that are able to bind and inhibit the influenza virus at concentrations of 10−7–10−8M.

    6. The Binding Mode of Progesterone to Its Receptor Deduced from Molecular Dynamics Simulations (pages 155–161)

      Tiziana Mordasini, Alessandro Curioni, Roberta Bursi and Wanda Andreoni

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390026

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      Piecing together the puzzle: Molecular dynamics simulations of progesterone in complex with its receptor in solution (see figure) were used in combination with an X-ray crystal structure and site-directed mutagenesis results from the literature to solve the puzzle of how the hormone and receptor bind. This multiple-method approach offers an efficient procedure for unraveling ligand–protein binding whenever simulations based on conventional force fields might misrepresent chemical features of the ligand.

    7. DMACM-Caged Adenosine Nucleotides: Ultrafast Phototriggers for ATP, ADP, and AMP Activated by Long-Wavelength Irradiation (pages 162–170)

      Daniel Geißler, Wolfgang Kresse, Burkhard Wiesner, Jürgen Bendig, Helmut Kettenmann and Volker Hagen

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390027

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      Switching on the bioactivity: [7-(dimethylamino)coumarin-4-yl]methyl-caged (DMACM-caged) compounds of adenosine nucleotides have been developed. They serve as excellent biologically inactive sources of the biomolecules. Their usefulness for physiological studies is demonstrated (see picture; ATP=adenosine triphosphate, IP3=inositol 1,4,5-tris(phosphate)). In cultures of mouse astrocytes, as well as in brain tissue slices from mice, photoreleased ATP produced Ca2+ ion waves, a specific form of glial communication.

    8. NMR Structure of the Single QALGGH Zinc Finger Domain from the Arabidopsis thaliana SUPERMAN Protein (pages 171–180)

      Carla Isernia, Enrico Bucci, Marilisa Leone, Laura Zaccaro, Paola Di Lello, Giuseppe Digilio, Sabrina Esposito, Michele Saviano, Benedetto Di Blasio, Carlo Pedone, Paolo V. Pedone and Roberto Fattorusso

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390028

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      Grasping fingers: The first high-resolution structure of a classical zinc finger domain from a plant protein is presented. The synthesis and UV and NMR structural characterization of a 37 amino acid region of a SUPERMAN protein complexed to a Zn2+ ion (Zn–SUP37; see figure) is reported. The existence of a DNA recognition code peculiar to the QALGGH zinc finger domain that includes all or some of the amino acid residues at positions −1, 2, and 3 (numbered relative to the N terminus of the α helix) and possibly other positions at the C-terminal end of the recognition helix is proposed. This study further confirms that the zinc finger domain, though very simple, is an extremely versatile DNA binding motif.

    9. D-Tyrosine as a Chiral Precusor to Potent Inhibitors of Human Nonpancreatic Secretory Phospholipase A2 (IIa) with Antiinflammatory Activity (pages 181–185)

      Karl A. Hansford, Robert C. Reid, Chris I. Clark, Joel D. A. Tyndall, Michael W. Whitehouse, Tom Guthrie, Ross P. McGeary, Karl Schafer, Jennifer L. Martin and David P. Fairlie

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390029

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      Damping down the inflammation: D-Tyrosine is a simple chiral precursor to a series of potent new inhibitors of hnpsPLA2-IIa (see scheme; R1, R2, R3 and X=varied). Thirteen compounds have IC50 values less than 1 μM. A 2.2-Å resolution crystal structure of one inhibitor–enzyme complex shows the expected active site location, with the inhibitor chelated to a Ca2+ ion through carboxylate and amide oxygen atoms, H bonded through its amide NH group to His48 and with multiple hydrophobic contacts and a T-shaped interaction between an aromatic group and His6. Antiinflammatory activity is demonstrated for two compounds after oral administration to rats at 5 mg kg−1 day−1.

    10. Solid-Phase Synthesis and Biological Activity of a Thioether Analogue of Conotoxin G1 (pages 186–194)

      Jon Bondebjerg, Morten Grunnet, Thomas Jespersen and Morten Meldal

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390030

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      Tying toxic knots: A bicyclic thioether analogue of α-conotoxin G1 (see scheme) was synthesized on the solid phase and the inhibitory activity (IC50 value) at the muscular nicotinic acetylcholine receptor was determined. The synthetic procedure used provides a general tool for introducing conformational constraints into a peptide to mimic the disulfide-knotted motif found in naturally occurring toxins. The IC50 values recorded suggest that it may be possible to produce analogues as active as the parent toxin in the future.

    11. Photocrosslinking in Ruthenium-Labelled Duplex Oligonucleotides (pages 195–202)

      O. Lentzen, J.-F. Constant, E. Defrancq, M. Prévost, S. Schumm, C. Moucheron, P. Dumy and A. Kirsch-De Mesmaeker

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390031

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      Inhibition of gene expression may eventually be achieved by photocrosslinking, as evidenced by a series of oligonucleotide duplexes derivatised by an oxidising RuII complex (see figure). The conditions required to obtain high yields of photoadduct were determined and it was observed that the yield depends greatly on geometrical factors as well as the ionisation potentials of the nucleobases involved. The oligonucleotide photoadducts studied are able to block a type-III exonuclease enzyme, which may open up possibilities for gene expression inhibition and could thus be therapeutically useful.

    12. Behavior Of Silica Aerogel Networks as Highly Porous Solid Solvent Media for Lipases in a Model Transesterification Reaction (pages 203–210)

      H. El Rassy, A. Perrard and A. C. Pierre

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390032

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      Media impact: A new type of solid medium, aerogels, has been used to immobilize lipases (see figure). Aerogels have an extremely high porosity not achievable with other materials. The hydrophobic/hydrophilic chemistry of aerogels can be tailored so that the particles contain a liquid different from that in the main liquid reaction medium. This technique opens the way to the use of solid aerogel particles to monitor enzyme performance in a manner somewhat similar to that of liquid emulsions.

    13. Substrate Specificity of Mutants of the Hydroxynitrile Lyase from Manihot esculenta (pages 211–216)

      Holger Bühler, Franz Effenberger, Siegfried Förster, Jürgen Roos and Harald Wajant

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390033

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      Tryptophan is a bulky doorman: The enantioselective formation of (S)-cyanohydrins from a variety of aldehydes catalyzed by the hydroxynitrile lyase from Manihot esculenta or one of several mutants was investigated (see scheme). Tryptophan128, which blocks the channel entrance to the active site of the wild-type enzyme, was substituted by amino acids with decreasing size. As demonstrated in the preparation of the pyrethroid precursor (S)-3-phenoxybenzaldehyde cyanohydrin, the bulkiness of the amino acids plays an important role as determinant for reactivity and substrate specificity.

    14. In Vitro Selection of N-Peptide-Binding RNA on a Quartz-Crystal Microbalance to Study a Sequence-Specific Interaction between the Peptide and Loop RNA (pages 217–220)

      Hiroyuki Furusawa, Akiko Murakawa, Shinobu Fukusho and Yoshio Okahata

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390034

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      On-the-spot RNA selection: N peptide or mutated N peptide was immobilized on a highly sensitive 27-MHz quartz-crystal microbalance, which was used as a monitoring and evaluation device for in vitro selection of RNA sequences that bind to these peptides (see figure). This method allowed the study of a sequence-specific interaction of the peptide with loop RNA in situ and without the use of labeling techniques and time-consuming separate binding assays.

    15. External Regulation of Hairpin Ribozyme Activity by an Oligonucleotide Effector (pages 220–224)

      Stéphanie Vauléon and Sabine Müller

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390035

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      Outside influence: External regulation of hairpin ribozyme derivatives by oligonucleotide effectors offers the possibility of switching activity in a defined way and opens up attractive methods for structure and function analysis. An oligonucleotide effector was used to reactivate two inactive mutants of the hairpin ribozyme (see figure). The effector replaced the mutated sequence of the ribozyme and restored its catalytically competent conformation. The same technique could be used to interrupt and then reactivate the catalytic cycle at specific steps and thus to study the structure and function of other ribozymes.

    16. Synthesis of Thioether-Linked Analogues of the 2,3-Sialyl-TF and MECA-79 Antigens: Mucin-Type Glycopeptides Associated with Cancer and Inflammation (pages 224–228)

      Lisa A. Marcaurelle, Matthew R. Pratt and Carolyn R. Bertozzi

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390036

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      Sulfur linkages: A strategy for the synthesis of a glycosylated analogue of a 17 amino acid fragment of the P-selectin glycoprotein ligand-1 (PSGL-1) is reported. A 2-azido-3-thiogalctose-Thr analogue was incorporated into the peptide by 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis, and higher-order oligosaccharides corresponding to the 2,3-sialyl-TF (STF) and MECA-79 antigens were generated by alkylation of the corresponding 3-thioGalNAc with N-bromoacetamido sugars (see scheme).

    17. Modelling of Photointermediates Suggests a Mechanism of the Flip of the β-Ionone Moiety of the Retinylidene Chromophore in the Rhodopsin Photocascade (pages 228–231)

      Masaji Ishiguro, Takahiro Hirano and Yoshiaki Oyama

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390037

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      Flip out! A model of the bathorhodopsin chromophore (see scheme) generated by molecular dynamics simulation suggests a twisted conformation of the C11[DOUBLE BOND]C12 bond caused by steric interaction between the 13-methyl group and Cys183. The twisted double bond may be involved in the flip of the β-ionone moiety toward transmembrane segments 3 and 4 in the formation of lumirhodopsin.

    18. DNA with γ-Aminopropyltriethoxysilane Switches between B- and C-Form Structures under Thermal Control (pages 232–234)

      Masanori Yamada, Motoyoshi Nomizu, Shuya Satoh, Kousaku Ohkawa, Hiroyuki Yamamoto and Norio Nishi

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390038

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      A DNA thermostat: Double-stranded DNA complexed with γ-aminopropyltriethoxysilane (APTES) possesses the B-form structure at 35 °C and the C-form structure at 4 °C (see figure). Tris-(1,10-phenanthroline)ruthenium(II) specifically binds to the DNA–APTES complex at 4 °C, which suggests that the DNA structures of the DNA–APTES complex can be switched by thermal control. The DNA–APTES complex could potentially be useful for study of DNA structure as well as in novel materials for optical resolution with thermal control, thermal separation of mutagenic molecules, or thermal sensors.

    19. Preview: ChemBioChem 2-3/2003 (page 238)

      Article first published online: 27 FEB 2003 | DOI: 10.1002/cbic.200390041