Issue Date: January 5, 2004
Nutlins crack protein interactions
Researchers at Hoffmann-La Roche in Nutley, N.J., have identified a class of antitumor agents that disrupt a protein-protein interaction that can lead to cancer. The tumor suppressor protein p53 protects cells from turning cancerous by triggering a cascade of reactions that leads stressed cells to commit suicide. The protein Mdm2--which is overproduced in many human tumors--binds p53, preventing the tumor suppressor from carrying out its work. By screening a library, molecular oncologist Lyubomir T. Vassilev and his team identified a series of cis-imidazoline analogs--dubbed "nutlins"--that displace p53 from its complex with Mdm2 at nanomolar concentrations [Science, published online Jan. 2, http://www.sciencemag.org/cgi/content/abstract/1092472v1]. One nutlin (nutlin-3, shown) significantly inhibited tumor growth when orally administered to mice. The team used X-ray crystallography to show that nutlins use their two halogenated phenyl groups and an ethyl or isopropyl ether group to block the p53 binding site on Mdm2. The study reinforces the idea that small-molecule inhibitors of protein-protein interactions might make valuable therapeutics.
Light-triggered DNA self-repair
An artificial nucleic acid enzyme fixes thymine dimers with the help of long-wavelength light [Proc. Natl. Acad. Sci. USA, published online, http://www.pnas.org/cgi/doi/10.1073/pnas.0305943101]. From a random sequence DNA library, chemist Dipankar Sen of Simon Fraser University, in British Columbia, selected a 42-nucleotide strand that needs only light of about 305–310 nm to repair lesions caused by shorter wavelength UV light. Such an enzyme is intriguing, Sen says, because it proves for the first time that nucleic acids can repair UV-induced thymine dimers. And it suggests that in an early RNA world, protein enzymes or even protein cofactors may not have been required to maintain nucleic acid integrity. The nucleic acid enzyme also has a few interesting mechanistic similarities to protein photolyase enzymes that perform the same task. Gerald F. Joyce at Scripps Research Institute says this work certainly proves the principle of nucleic acid photo-triggered DNA repair. But he cautions that the laboratory-created enzyme can't be considered a historical remnant of an early RNA world.
The world's smallest platinum, palladium, and silver nanotubes, with inner diameters of 3–4 nm and outer diameters of 6–7 nm, have been made by a group from Miyazaki University, in Japan [Angew. Chem. Int. Ed., 43, 228 (2004)]. Noble-metal nanotubes could be used as electrodes in batteries or in fuel cells and as environmental catalysts. Applied chemistry professor Tsuyoshi Kijima and coworkers use equimolar amounts of two different-sized surfactants to create a hexagonal liquid crystal of rodlike micelles as a template on which to grow the tiny tubes. In aqueous solution, the hydrophobic portions of the surfactants form the interior of a micelle cylinder, defining the inner region of the tubes. Noble-metal salts are confined to the hydrophilic outer layer of the micelle cylinder, where they are reduced with hydrazine to form the metallic tubes. A mixture of medium and large surfactants was essential for nanotube formation because it makes the aqueous portion of the micelle, and therefore the tube, thicker. Attempts to make thinner tubes using just one of the surfactants led to mesoporous or bulk metals. Kijima suggests that the system could be used generally to make nanotubes.
Measuring small organic aerosols
Although organic compounds can make up more than half of the mass of aerosol particles smaller than 2.5 µm in diameter, no good methods have been available to obtain information about individual components in real time. Now, chemistry professor Murray V. Johnston and his coworkers at the University of Delaware, Newark, describe a method called photoionization aerosol mass spectrometry for the real-time analysis of the organic components in particles smaller than 300 nm [Anal. Chem., 76, 253 (2004)]. The particles are collected on a probe, which is irradiated with pulsed infrared radiation to vaporize the organic components. The vaporized organic compounds are ionized with minimal fragmentation using vacuum ultraviolet radiation. The ions are then analyzed using time-of-flight mass spectrometry. Using this method, Johnston and his team can identify and quantify organic compounds in the picogram range in aerosols from atmospherically relevant sources, such as diesel and gasoline engine exhaust. The instrument is currently sensitive enough for smog chamber measurements with less than one-minute time averages, and work is under way to improve sensitivity so that similar measurements can be made with ambient aerosols.
Soot's role in climate change
Soot--a mostly black carbon by-product of burning coal and diesel fuel--has had a larger-than-realized effect on global warming, according to James E. Hansen and Larissa Nazarenko, both of NASA Goddard Institute for Space Studies [Proc. Natl. Acad. Sci. USA, published online, http://www.pnas.org/cgi/doi/10.1073/pnas.2237157100]. The researchers use a computer model to simulate the effects of greenhouse gases and other factors on world climate. The model incorporates data from NASA's Terra and Aqua satellites, which monitor changing snow cover and effects of soot on snow. The results show that warming from soot in snow and ice accounts for 25% of the global warming observed between 1880 and 2000. Hansen and Nazarenko report that soot's effect on snow albedo--solar energy reflected back to space--may contribute to trends toward early springs in the Northern Hemisphere, thinning Arctic sea ice, and melting glaciers and permafrost. Although soot has had a substantial role in altering climate, greenhouse gases have been the primary cause of climate warming during the past century and will be an even larger cause for the rest of this century, Hansen cautions.
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