SCIENCE & TECHNOLOGY CONCENTRATES
Using electron microscopy, researchers have amassed new insights about how the hormone leptin interacts with its receptor (Mol. Cell, DOI: 10.1016/j.molcel.2012.09.003). Signals from leptin, which is secreted by fat tissue, affect metabolism. This biochemical pathwayhasintriguedobesitydrugresearchers for more than a decade. But the arrangement of leptin’s signaling complex is in dispute, with camps proposing either a 2:2 or a 2:4 ratio of leptin to its receptor. Georgios Skiniotis and colleagues at the University of Michigan now provide strong evidence that the ratio is 2:2. They observed two copies of leptin that engaged two copies of the rod-shaped receptor, locking the floppy rods into place. They propose that this locking mechanism is key for signaling. The next step, Skiniotis says, will be to determine a structure of the complex that includes Janus kinase, an enzyme that mediates leptin signaling and is itself a drug target for cancer and immune disorders. Skiniotis adds that the mechanism of leptin signaling parallels that of related proteins, such as interleukin-6, which is implicated in cancer.—CD
LIMITED FLAVORS FOR DNA-LINKED PARTICLES DNA’s ability to selectively bind to complementary sequences can be used to program the formation of materials through the selfassembly of DNA-functionalized particles. Research by physicist Paul M. Chaikin and chemist Nadrian C. Seeman of New York University and coworkers now shows that “multiflavored” particles, where each flavor is a different DNA sequence, can bind with many other particles to make complex materials (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1207356109).Theteamuseda computational approach to find the practical limit of different flavors that can be on a single particle. They determined that a 2-μm colloidal particle can handle up to 40 flavors. The upper limit of DNA flavors on a single particle is dictated both by entropy costs and by the number of unique sequences that avoid nonspecific binding. Any sequences with overlaps of five or more base pairs, which could bind sequences other than their intended partner, can’t be used. For the 11-base-pair sequences that the NYU researchers use, such a rule leaves a maximum of 73 available flavors out of more than 4 million possible sequences.—CHA
A templating process that creates a porous surface layer adds new reactant selectivity to robust metal-oxide catalysts, chemists report (Nat. Chem., DOI: 10.1038/nchem.1477). Supported and bulk oxides catalyze a variety of economically important reactions. Although the oxides may target specific functional groups, they typically can’t discriminate by molecule size, as crystalline microporous materials do. A group led by Northwestern University’s Justin M. Notestein has now developed a way to include size selection by using atomic layer deposition to add a porous film on top of oxide catalyst particles. Notestein and colleagues attached Attached to TiO2 (green), p-tertbulky, poorly packed templating ligands butylcalix[4]arene molecules provide the template to create reactant-limiting to the surface of TiO2 particles. They holes in an added Al2O3 layer (blue). then added a thin, inert Al2O3 layer that adhered to the TiO2 and surrounded the template molecules. Removing the template molecules left cavities 2 nm wide and 2 nm deep. The researchers used the porous-layer-coated particles to selectively photooxidize benzyl alcohol over 2,4,6-trimethylbenzyl alcohol and reduce nitrobenzene over nitroxylene.—JK
INSECT PHEROMONES MADE CATALYTICALLY From the promising new family of Z-selective olefin metathesis catalysts comes a synthetic strategy for preparing insect pheromones (Angew. Chem. Int. Ed., DOI: 10.1002/ anie.201206079). Although highly useful for environmentally friendly insect control, cis-olefin-containing insect pheromones are difficult to synthesize, and their production generates large amounts of waste. Last year, Caltech’s Robert H. Grubbs and colleagues used one of the ruthenium-based Z-selective catalysts pioneered by Grubbs’s group to synthesize a monounsaturated cis-olefin-containing pheromone. Now, Grubbs’s group has expanded the catalyst’s repertoire to include short, simple syntheses of nine lepidopteran pheromones that EPA has approved for use as insecticide alternatives. Starting with oleyl alcohol and 11-eicosenol derived from vegetable oils, the group prepared the pheromones in good yields at mild temperatures, with better than 80% Z-selectivity in most cases. The researchers envision this strategy could be
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generalizedtomanyanalogouspheromones and be practical on an industrial scale.—EKW
LAMPREY ANTIBODIES SNAG SUGARS Lampreys are notorious for sucking blood, but they also produce antibody-like proteins with a taste for sugar that could help detect and deliver drugs to tumors. Dubbed lambodies, these proteins bind polysaccharides, or glycans, more tightly and specifically than most conventional antibodies, researchers have found (ACS Chem. Biol., DOI: 10.1021/ cb300399s). The discovery provides a new source of reagents for detecting glycans linked to disease, such as those that decorate proteins and lipids made by tumor cells. To find lambodies that bind glycan biomarkers, Zeev Pancer of the University of Maryland’s Institute of Marine & Environmental Technology and colleagues screened a library of 100 million yeast clones that each expressed a different lambody on their surface. The researchers identified lambodies with affinities of up to 100 times that of conventional antibodies for glycans, including one linked to HIV and two found on most types of cancer cells. Pancer’s group aims to developalambody-baseddiagnosticbiosensor to detect glycan biomarkers of cancer in patients’ blood, urine, or saliva.—DL
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POROSITY ASSISTS SELECTIVITY
HOW LEPTIN SIGNALS
