SCIENCE & TECHNOLOGY CONCENTRATES
UBIQUITIN VARIANTS REVEAL NEW INHIBITORS
WORM QUANTUM DOT FACTORIES
STREAMLINED ROUTE TO HYDROXYLATED STEROIDS A strategy to install multiple hydroxyl groups on complex steroid frameworks has allowed chemists to streamline and scale up the synthesis of ouabagenin, a member of the cardenolide class of drugs used for treating congestive heart failure. Hans Renata, Qianghui Zhou, and Phil S. Baran of Scripps Research Institute in California anticipate that their approach will provide chemists with a versatile way to modify natural and synthetic steroid structures to lower toxicity and improve therapeutic properties (Science, DOI: 10.1126/science.1230631). Ouabagenin’s complex array of hydroxyl groups has made it difficult to synthesize: The previous best synthesis took 41 steps and had less than 1% overall yield. Starting with low-cost cortisone acetate, which has one hydroxyl group, Baran’s team used so-called relay reactions to transfer electronic and stereochemical properties from one carbon to another in the steroid framework. This facilitated C–H and C–C bond activation and C–O bond formation, achieving results similar to enzymemediated oxidations. They produced ouabagenin, which has six hydroxyl groups, on a gram scale in 21 steps.—SR
Not only do earthworms fertilize soil and help catch fish, but the wriggly creatures are also capable of manufacturing semiconductor nanoparticles called quantum dots, according to researchers at King’s College London (Nat. Nanotechnol., DOI: 10.1038/nnano.2012.232). Scientists have previously biosynthesized nanoparticles by hijacking the cellular machinery inside bacteria, viruses, and fungi, but “we’re pretty sure this is the first time this has been intentionally achieved in a higher animal,” says Mark Green, who led the research team. To prove the worms capable Earthworms manufacture of the feat, Green, Stephen R. Stürzenbaum, CdTe quantum dots, and coworkers put the animals in soil laced with which can be used to light cadmium chloride and sodium tellurite. When up ovarian cancer cells; they later cut the worms open, they found 2-nmquantum dots are green and cell nuclei are blue. diameter CdTe quantum dots. The researchers think the earthworms sequester the heavy metals as part of a detoxification mechanism. After harvesting the wormmade dots, the team demonstrated their utility as imaging agents: The particles are taken up by ovarian cancer cells and emit green light after being excited at blue wavelengths.—LKW STEPHEN STÜRZENBAUM
Scientists have developed and exploited a set of ubiquitin variants that could lead to a better understanding of the way the peptides help manage cellular functions. Ubiquitins regulate cells by a signaling process that is activated via their attachment to key cellular proteins. Deubiquitinating enzymes later remove these ubiquitin tags from the proteins. The enzymes also play a role in some cancers and neurodegenerative, hematologic, and infectious diseases. Inhibitors can be used to study the enzymes’ roles, but only a few weak inhibitors have been identified. In Science, Sachdev S. Sidhu of the University of Toronto and coworkers report that they have identified potent deubiquitinating enzyme inhibitors by screening a combinatorial library of ubiquitin-like compounds (DOI: 10.1126/science.1230161). They also screened the library to find agents that inhibit enzymes that conjugate ubiquitins to proteins or recognize ubiquitin tags. The ubiquitin variants “will serve as useful genetic probes to assess and modulate ubiquitin system function in vivo,” they write.—SB
PHOTOCHEMISTRY ALTERS POLLUTANT ANALYSIS Scientists have an array of analytical and computational tools to help monitor airborne pollutants such as volatile organic compounds (VOCs). But researchers at Peking University, in China, and the University of Colorado, Boulder, have discovered that photochemistry occurring while a pollutant molecule travels from its source to a monitoring instrument can interfere with the accuracy of a popular data analysis method (J. Geophys. Res.: Atmos., DOI: 10.1029/2012jd018236). Min Shao and colleagues used gas chromatography and mass spectrometry to monitor VOC emissions in Beijing, relying on a data-processing technique known as positive matrix factorization (PMF). Although some methods in the same class as PMF try to take into account atmospheric photochemical reactions, such interferences in the more commonly used PMF method have not been well recognized. For example, with the Beijing data, PMF failed to completely separate human and nonhuman VOC sources. The method also mistakenly identified some VOCs as coming from separate sources, when they were actually from the same source but in different oxidation states. The researchers caution that when using PMF-based results, including those already reported
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in the literature, photochemical influences should be taken into account.—EKW
HOST-GUEST APPROACH TO COMBO CATALYSIS With the use of a supramolecular host-guest framework, researchers at the University of California, Berkeley, have developed a protocol for bringing together organometallic catalysts and enzymes to mediate one-pot tandem reactions (Nat. Chem., DOI: 10.1038/ nchem.1531). The work highlights a strategy for carrying out chemical transformations not possible with either type of catalyst alone while also preventing adverse interactions between the catalysts and extending their lifetimes. Z. Jane Wang, F. Dean Toste, and coworkers previously found that sheltering a gold complex in a Ga4L6 framework, where L is a benzoyl-naphthalene ligand, yields a host-guest species that catalyzes allene alkoxylation more actively than does the free gold complex. The team has now shown that Au(I) or Ru(III) host-guest species can be paired with esterases or lipases to mediate multistep reactions. For example, the researchers used an enzyme to convert an allenic acetate to the corresponding alcohol and subsequently used a sheltered gold catalyst to cyclize the alcohol to form a substituted tetrahydrofuran.—MJ
