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Environment

Science Concentrates

February 7, 2005 | A version of this story appeared in Volume 83, Issue 6

Pheromone extends life in worms

A South Korean research group has structurally characterized and chemically synthesized a novel pheromone that postpones aging in worms. The finding could lead to drugs that control parasitic worms in animals and plants as well as to novel insights into aging and obesity in humans [Nature, 433, 541 (2005)]. When Caenorhabditis elegans worms find their environment crowded and inhospitable, they hibernate until food becomes available, effectively extending their life span. A team led by Young-Ki Paik of Yonsei University, in Seoul, has now completed a laborious, large-scale purification process to isolate the pheromone that induces such hibernation. Paik's team used mass spectrometry and NMR spectroscopy to determine the structure (shown) of the pheromone--dubbed daumone--and then designed a stereospecific, 10-step method to synthesize it. Both isolated and synthetic daumone induce the morphological changes that accompany worm hibernation. These results may shed light on the signaling pathway by which daumone induces hibernation, a pathway thought to be similar to those that lead to aging and obesity in humans.

Underreporting of CH3CCl3 use

European emissions of methyl chloroform (CH3CCl3) have declined greatly since the mid-1990s, but they are higher than reported by European companies. This is the conclusion of research conducted by Stefan Reimann of the Swiss Institute of Materials Science & Technology, Dübendorf, and his colleagues [Nature, 433, 506 (2005)]. CH3CCl3 was used widely as a solvent before it was found to be a stratospheric-ozone-depleting substance. Under the Montreal protocol, it is to be phased out globally by 2015. European emissions declined from about 60,000 metric tons per year in the mid-1990s to less than 3,400 metric tons per year in 2000–03, according to measurements Reimann did at atmospheric research stations in Ireland and Switzerland. CH3CCl3 consumption and emission data reported by European producers, however, add up to less than 100 metric tons per year. If Reimann's measurements are correct, European companies are severely underreporting use of CH3CCl3. Unrecorded sources must exist, Reimann says.

Polymer lights up membranes

Chemists at Ben Gurion University, Beersheva, Israel, have developed a way to visualize activity on cell membranes. The technique can be used to better understand membrane processes such as endocytosis and virus infection of cells. In drug discovery, it can help select compounds that exert a strong effect on cell membranes, a requirement for cell penetration. To observe membrane disruption, Raz Jelinek and coworkers attach patches of polydiacetylene to the cell surface [Angew. Chem. Int. Ed., 44, 1092 (2005)]. When the cell membrane is disturbed, the polymer undergoes a conformational change, which in turn brings about a color change. The polymer turns from blue to red and starts to fluoresce. Jelinek and coworkers demonstrate the principle by exposing polydiacetylene-labeled monocytic U937 leukemic cells to various drugs and to membrane perturbation processes and observing the effects by microscopy. They find that different drugs perturb the membranes of these cells differently--uniformly in some cases, as revealed by a uniform red fluorescence around treated cells, or localized, as shown by a single red fluorescent spot in other cases.

Scaffold-based drug design disclosed

Scaffold-based drug design, a rapid route to drug leads, has been used quietly for years, but now Kam Y. J. Zhang of Plexxikon, Berkeley, Calif., and coworkers have described it in the literature for the first time [Nat. Biotechnol., 23, 201 (2005)]. The technique is midway between high-throughput screening (HTS) and fragment-based design. In HTS, fast biochemical assays are used to test large numbers of druglike compounds for activity, and the best "hits" are optimized to create drug leads. In fragment-based design, slower biophysical methods such as NMR and crystallography are used to screen small numbers of very small building blocks for affinity to target sites, and hits are combined and built up to create drug leads. In scaffold-based design, HTS-type assays are used initially to screen intermediate numbers of scaffolds (larger size than fragments but smaller than druglike compounds). The hits are then validated and optimized by high-throughput cocrystallography of ligand-target pairs. Zhang and coworkers demonstrate the technique's robustness by using it to identify novel selective phosphodiesterase inhibitors with only two rounds of synthesis and seven structural analyses.

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Credit: © SCIENCE 2005
Credit: © SCIENCE 2005

Lasers move H2O between H-bonding sites

A laser-initiated method has been used to measure the energy required to move a water molecule from one hydrogen-bonding site on an amide molecule to another one on the same molecule. This experimental information--and subsequent calculations of the water molecule's favored path--will better the understanding of how the amide backbone of proteins interacts with its watery environment and may improve computational simulations of biological processes. Timothy S. Zwier and colleagues at Purdue University first prepared discrete gas-phase clusters containing a single water molecule hydrogen-bound to either the amide NH or the amide carbonyl of trans-formanilide. They then used lasers to selectively excite one of these isomers, causing its water molecule to move to the other site [Science, published online Feb. 3, http://dx.doi.org/10.1126/science.1106977]. By doing so, Zwier's team was able to measure the energy required to move the water molecule in either direction. Kenneth D. Jordan and coworkers at the University of Pittsburgh then used calculations to verify this energy and to locate the path the water molecule takes (time-lapse image shown above).

 

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