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Warfarin chiral switch in one efficient catalytic step

An atom-economical synthesis of single enantiomers of the anticoagulant warfarin has been achieved with organic catalysts. The route was developed by chemists Nis Halland, Tore Hansen, and Karl Anker Jørgensen at Aarhus University, in Denmark [Angew. Chem. Int. Ed., 42, 4955 (2003)]. The work lays the ground for a facile chiral switch for the widely used anticoagulant. The S enantiomer is more active than the R enantiomer. And because of the difference in the metabolism of the enantiomers, dosing with the racemic drug can be problematic. The Danish group prepares single-enantiomer warfarin by mixing at room temperature 4-hydroxycoumarin and benzylideneacetone in dichloromethane in the presence of an imidazolidine catalyst (10 mol %). Yields of up to 96% are achieved, with enantiomeric excesses of up to 82%, which may be raised to greater than 99.9% by a recrystallization in acetone/water.

 

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Carbon under pressure characterized

The form that graphite takes when compressed at ambient temperatures has long puzzled researchers. The substance's physical properties suggest something akin to diamond, but unlike various forms of diamond, when the so-called cold-compressed graphite returns to ambient pressure, it reverts to conventional graphite. A team led by University of Chicago graduate student Wendy L. Mao now has identified the material's elusive structure using inelastic X-ray scattering spectroscopy [Science, 302, 425 (2003)]. The researchers report that at 17 gigapascals of pressure, half of the C2C -bonds in graphite break and form -bonds with carbon atoms that are directly above or below one another in adjacent layers of graphite. The transient material is superhard and able to scratch diamond, as evidenced by cracks the material left in the diamond anvils of Mao's sample gasket. The researchers speculate that this reversible change in hardness could have intriguing applications as a pressure-dependent structural component.

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Prediction better than experiment

Genomewide analyses of protein interactions can magnify the inaccuracies of interaction data sets because the protein pairs that don't interact vastly outnumber those that do. A team led by Mark Gerstein, associate professor of molecular biophysics and biochemistry and computer science at Yale University, uses a statistical approach to improve genomewide predictions of yeast protein interactions [Science, 302, 449 (2003)]. They use two different networks of protein interactions, one predicted and one experimental. The predicted network includes data that are only weakly associated with protein interactions, such as mRNA expression. The experimental network includes experimentally derived protein interactions gleaned from the literature. More protein interactions were identified using the predictions than the experimental data. These predictions were then tested experimentally using tandem affinity purification tagging, in which a bait protein is employed to fish out interacting proteins. The team identified previously unknown protein interactions involving the nucleosome, the replication complex, and Nsr1, a protein complex involved with RNA processing. Go to the full story.

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Bacteria light up to arsenic

Well water contaminated with arsenic leaching from mineral deposits is a public health threat, particularly in Southeast Asia where millions of wells must be repeatedly tested for the toxic element. Chemical field tests involve simple colorimetric paper strips, but they are generally accurate to about 70 µg per L of arsenic, while drinking water standards are 50 µg per L or less. Bacterial biosensors with better sensitivity exist, but they have been limited to detecting arsenic in lab-based methods. Jan Roelof van der Meer of the Swiss Federal Institute for Environmental Science & Technology, Dübendorf, and coworkers have now modified strains of Escherichia coli to detect arsenic at 4 µg per L and developed field tests [Environ. Sci. Technol., 37, 4743 (2003)]. The researchers inserted genes for color-producing proteins--bacterial luciferase, -galactosidase, and green fluorescent protein--in E. coli and placed their production under control of the arsenite sensor protein. Field-testing is ongoing in Vietnam using the bacterial luciferase sensor.

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PLoS Biology launched

San Francisco-based Public Library of Science launched its first peer-reviewed, open-access scientific journal last week. At the same time, the journal made a splash with pre-issue publication of a paper reporting that monkeys can control a robotic arm with their thoughts. PLoS Biology users will be able to download, print, distribute, and reuse articles for free (http://www.plosbiology.org). Initially, traffic on the site was so heavy that its servers were overwhelmed. Users can also purchase the monthly print journal at cost. To cover publishing costs, authors of PLoS Biology articles will be charged a fee of $1,500 per article. Howard Hughes Medical Institute has agreed to give its investigators the money to pay these fees, and PLOS hopes that NIH and other funding organizations will do the same. PLOS intends to roll out PLoS Medicine in 2004. "Our aim is to catalyze a revolution in scientific publishing by providing a compelling demonstration of the value and feasibility of open-access publication," PLOS cofounders Patrick O. Brown of Stanford University School of Medicine; Michael B. Eisen of the University of California, Berkeley; and Harold E. Varmus of Memorial Sloan-Kettering Cancer Center write in the inaugural issue of PLoS Biology.

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