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Volume 5 Issue 9, September 2009

DNA-encoded libraries. Clark et al. (p 647) describe a new method for synthesizing DNA-encoded libraries that uses double-stranded DNA coding and a combination of enzymatic and chemical synthesis in a split-and-pool format. With this approach, the authors synthesized two libraries, the larger of which contains just over 800 million molecules, and rapidly selected novel, potent kinase inhibitors. The cover shows a microscopic view of affinity selection for DNA-linked compounds that bind to p38 MAP kinase. Cover art by Erin Dewalt, based on images provided by Kenneth Lind and Matthew Clark.

Volume 5 Issue 9

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  • How do we foster open scientific dialog in the digital age while respecting the integrity of the scientific process?

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  • A small-molecule inhibitor of the obligate dimeric protease of human Kaposi's sarcoma–associated herpesvirus was identified. The agent functions by a 'monomer trap' mechanism in which the compound binds to a partially unfolded monomer and disrupts the formation of the enzymatically active protease dimer.

    • Jean Chmielewski
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  • The functional architecture of dimeric or oligomeric GPCR signaling remains incompletely understood. Using a clever combination of receptor–G protein fusions and various receptor mutations, new research provides a glimpse into how oligomers might be arranged with respect to the G proteins they interact with.

    • Peter Zylbergold
    • Terence E Hébert
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  • Screening a library of expressed cyclic peptides identified clones that reverse the cytotoxicity of α-synuclein in yeast and Caenorhabditis elegans. The results suggest a new approach for intervention in Parkinson's disease, and perhaps a druggable target.

    • Charles P Scott
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  • A cocrystal structure of the enzyme that synthesizes selenocysteine reveals the elegantly simple recognition mechanism for the tRNA molecule for this '21st amino acid'. The structure resolves some mechanistic questions and allows for comparison of the tRNA-dependent synthesis of cysteine and selenocysteine.

    • Eugene G Mueller
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  • One of the primary functions of the Golgi apparatus is the assembly of glycans on macromolecules destined for secretion or the plasma membrane. A recent study describes the first step toward an artificial Golgi, based on a microfluidic chip and magnetic nanoparticles.

    • Ding Xu
    • Jeffrey D Esko
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