In this issue - pv

doi:10.1038/nchembio0108-v

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Chemical biology expands its horizons - p1

doi:10.1038/nchembio0108-1

Building on its foundations in chemistry, chemical biology is now extending its reach to understand and manipulate increasingly complex biological systems.

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Searching for a wrench to throw into the splicing machine - pp3 - 6

Melissa S Jurica

doi:10.1038/nchembio0108-3

Many macromolecular complexes function as nanoscale machines performing important cellular jobs. However, their complex and dynamic natures pose challenges for detailed structure-function analysis. Small-molecule inhibitors, which can be identified by high-throughput screening, provide important leverage into the study of macromolecular assemblies by allowing researchers to capture transient intermediate states and probe important functional components.

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Drugs in action - pp7 - 11

Ulrike S Eggert & Giulio Superti-Furga

doi:10.1038/nchembio0108-7

How do drugs work? What molecular changes do they cause in cells and in organisms? Is there a paradigm shift in the way we can predict and appreciate the impact of small molecules on biological systems in the 21^st century? These were some of the questions addressed at a meeting in Vienna in August 2007.

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Engineering ingenuity at iGEM - p13

Catherine Goodman

doi:10.1038/nchembio0108-13

As an international competition that places a premium on creative thinking and the development of a research community of all ages, iGEM is helping synthetic biology grow.

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Small-molecule dissection of BMP signaling - pp15 - 16

Gregory J Anderson & Deepak Darshan

doi:10.1038/nchembio0108-15

Analysis of the multifunctional bone morphogenetic protein (BMP) signaling pathway has been hampered by the lack of specific reagents for discriminating downstream signaling events. A new study uses a novel zebrafish embryo screen to identify dorsomorphin, the first small-molecule inhibitor of BMP signaling, and shows its application in fields as diverse as osteogenesis, developmental patterning and iron homeostasis.

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See also: Article by Yu et al.

IP₇ guards the CDK gate - pp16 - 17

John D York & Daniel J Lew

doi:10.1038/nchembio0108-16

Analyses of mutants affecting the synthesis of inositol phosphates have uncovered a variety of new roles for these small molecules in cells, but identification of their physiological targets has lagged behind. New studies on the yeast phosphate starvation response have brought the inositol pyrophosphate IP₇ and its mechanism of action into sharp focus.

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See also: Article by Lee et al.

SAR by HCS - pp18 - 19

Paul Lang

doi:10.1038/nchembio0108-18

The combination of high-content small-molecule screening information with computational tools offers the opportunity to obtain structure-activity relationships from complex cell-based data.

Full Text - SAR by HCS | PDF (2,892 KB) - SAR by HCS

See also: Article by Young et al.

Chemical "knockout" challenges the amphotericin B channel model - pp19 - 20

Sergey A Kozmin

doi:10.1038/nchembio0108-19

Charge pairing between neighboring amphotericin B molecules inserted into the membrane is believed to significantly stabilize supramolecular channel architecture. Now the synthetic "knockout" of a carboxylic acid in amphotericin B, generated in an exacting ten-step chemical sequence, shows this interaction is not required for function.

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What determines the speed limit on enzyme catalysis? - pp21 - 22

Hans Frauenfelder

doi:10.1038/nchembio0108-21

Though the chemical mechanisms of many enzymes have been elucidated, the mechanisms by which specificity and rate acceleration are achieved remain less explored. A new study suggests that physically controlled processes, such as active site access and organization, are rate limiting for enzymatic catalysis.

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Research Highlights - p23

doi:10.1038/nchembio0108-23

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