Science Concentrates

Vitamin C turns away from the dark side

A new study endeavors to rescue the reputation of vitamin C (ascorbate) from earlier findings that suggested it could cause toxic compounds to be produced. Three years ago, Ian A. Blair and coworkers at the Center for Cancer Pharmacology of the University of Pennsylvania reported in vitro experiments showing that vitamin C (center in figure) can degrade oxidized lipids, forming lipid peroxidation products like 4-hydroxy-2-nonenal (top) [Science, 292, 2083 (2001)]. Such compounds can damage DNA and genes. Now, Jan F. Stevens and coworkers at Linus Pauling Institute at Oregon State University find that the process doesn't stop there--that vitamin C continues to react with the peroxidation products to form apparently harmless conjugates (bottom) [Proc. Natl. Acad. Sci. USA, published online, http://dx.doi.org/10.1073/pnas.0408433102]. In human studies, they found high levels of such conjugates in blood plasma. The findings suggest vitamin C may prevent genetic damage by removing such peroxidized lipids--and that may explain in part how the vitamin helps prevent diseases like cancer and heart disease.

Metal-free Suzuki reaction retracted

Last year, chemists reported that a popular carbon-carbon bond-forming reaction could be run in the absence of its expensive palladium catalyst. They've now shown that trace palladium contaminants in a commercial reagent were responsible for the reportedly metal-free Suzuki reaction. The Suzuki reaction--the palladium-catalyzed coupling of aryl halides and arylboronic acids--is widely used to synthesize pharmaceutical and agrochemical active ingredients because of its versatility. Palladium is expensive and residual metal in the product may pose environmental concerns, so it seemed almost too good to be true when Nicholas E. Leadbeater of the University of Connecticut, Storrs, reported microwave-assisted Suzuki-type couplings in the absence of palladium [Angew. Chem. Int. Ed., 42, 1407 (2003)]. At the time, Leadbeater's team took great care to check for low levels of palladium and other transition-metal contaminants, excluding metal contamination above 0.1 ppm. Now, however, they've discovered that palladium contaminants at a concentration as low as 50 ppb found in commercially available sodium carbonate are responsible for the "metal-free" Suzuki reaction [J. Org. Chem., published online Dec. 8, http://dx.doi.org/10.1021/jo48531j].

Nanotube glucose sensors

Carbon nanotubes form the basis of a new near-infrared optical sensor for glucose, in which changes in the nanotube's electronic properties lead to changes in its fluorescence. Michael S. Strano and his coworkers at the University of Illinois, Urbana-Champaign, assemble a monolayer of the enzyme glucose oxidase on nanotubes [Nat. Mater., published online Dec. 12, http://dx.doi.org/10.1038/nmat1276]. Potassium ferricyanide is then adsorbed to the surface. When glucose binds to the glucose oxidase, hydrogen peroxide is produced, which can form a complex with the ferricyanide. The interaction modulates the electronic properties of the nanotubes such that it changes their fluorescence in a way that depends on the glucose concentration. The researchers load the nanotube sensors into a dialysis capillary that traps the nanotubes but allows glucose to enter freely. The capillary can be inserted in tissue and imaged through the skin. Such a device could potentially be useful as a glucose monitor. The researchers predict that the same sensing strategy could be used for a wide range of biomolecules.

Sweet route to cyclic peptides

A new chemoenzymatic approach for creating libraries of cyclic glycosylated peptides, a promising class of druglike compounds, has been devised by Chi-Huey Wong of Scripps Research Institute, Christopher T. Walsh of Harvard Medical School, and coworkers [Chem. Biol., 11, 1635 (2004)]. Cyclic peptides are considered useful for drug discovery, but without glycosylation, they don't enter cells easily, and cyclizing linear peptide substrates is synthetically difficult. Cyclic glycosylated peptides enter cells more easily, but the process of cyclizing peptides first and adding sugars later also has serious synthetic drawbacks, whether done chemically or enzymatically. In the new technique, linear glycosylated peptides are first created by solid-phase peptide synthesis of glycosylated amino acid building blocks. The linear glycosylated peptides are then macrocyclized enzymatically (using the thioesterase domain from tyrocidine synthetase) to form a range of cyclic glycosylated peptides in high yield. This versatile chemoenzymatic approach should make it easier to create large libraries of natural-product-like cyclic glycosylated peptides.

Fat hormone mimics insulin

Visceral fat--the especially unhealthy fat surrounding organs--secretes a molecule that mimics insulin. The protein, PBEF, has been observed previously in the immune system. Iichiro Shimomura at Osaka University and coworkers rediscovered it, however, while looking for hormones secreted by visceral fat, the type of fat most often associated with metabolic syndrome [Science, published online Dec. 16, http://dx.doi.org/10.1126/science.1097243]. The Japanese group renamed the molecule visfatin and found that it has an insulin-like ability to lower blood sugar levels. In fact, at similar concentrations, visfatin and insulin have a comparable ability to stimulate glucose uptake. (Visfatin normally circulates at concentrations 3 to 10% of that of insulin.) Intriguingly, the authors say, visfatin mimics insulin by binding to the insulin receptor without interfering with the binding of insulin itself. The discovery, they say, may lead to creation of a visfatin-like drug for diabetes that magnifies insulin's effects without dampening insulin's own effects.

RETRACTION

The paper described in this article has since been retracted (Science, DOI: http://www.sciencemag.org/cgi/content/full/307/5708/426).

Retraction notice published in Science October 26, 2007: http://www.sciencemag.org/cgi/content/full/sci;318/5850/565b