Science Concentrates DRUG DISCOVERY
▸ New target for antiinflammatory agents
Computational model of the NSAID fenbufen (green) bound to the active site of caspase-3. 10.1016/j.chembi ol.2017.02.003). NSAIDs such as AdO vil and aspirin are OH primarily cyclooxygenase inhibitors O but hit other targets as well, causing Fenbufen side effects such as stomach pain, heartburn, and bleeding. The addition of caspases to the list of NSAID targets could aid understanding of the drugs’ anti-inflammatory effects and help lead to the design of new agents with reduced side effects. Hang Hubert Yin and coworkers at the University of Colorado, Boulder, studied NSAID targeting in cells exposed to inflammatory stimuli that boost caspase production. Such conditions have not been widely used before in NSAID studies, the researchers say, even though patients with inflammatory conditions often take NSAIDs. Yin’s group shows that under inflammatory conditions, some NSAIDs bind to a common caspase active-site motif and therefore inhibit several types of caspases. “We are currently working on novel, selective caspase inhibitors, hoping to develop the next generation of anti-inflammation drugs,” Yin says.—STU BORMAN
MATERIALS
▸ Chemists create colloidal clathrate crystals As denizens of DNA, Chad A. Mirkin and his group at Northwestern University have
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C&EN | CEN.ACS.ORG | MARCH 6, 2017
Micrographs show the structure of a human tooth (left) and a synthetic enamel made of zinc oxide columns.
NANOMATERIALS
Synthetic tooth enamel has bite Scientists have created a new synthetic material with the properties of tooth enamel, setting the stage for advances in tooth repair or replacement (Nature 2017, DOI: 10.1038/nature21410). Tooth enamel from all species has a similar structure: microsized ceramic columns in a soft protein matrix. An international team led by Nicholas A. Kotov of the University of Michigan, Ann Arbor, prepared arrays of micrometer-scale zinc oxide columns to form “nanowire carpets.” Then the researchers embedded the columns in a polyallylamine matrix. They built up the material by repeating the process, adding more layers of the polymer-impregnated columns on top of each other. The material has a collection of properties—stiffness, density, and vibrational damping—that are similar to or better than those of tooth enamel and that haven’t been combined in one synthetic material before. More work needs to be done to scale up to the size of teeth without defects. But, the authors write, “our replication of columnar nanocomposites opens a new approach to the design of load-bearing, vibration- and aging-resistant, light materials.”—ELIZABETH WILSON
used the biopolymer in combination with metal nanoparticles to assemble hundreds of differently shaped micrometer-scale colloidal crystals. Even so, they have just come up with one that hasn’t been seen before: a colloidal clathrate. The trick in making the clathrates, which are known
for their cavities that can house molecules for storing, delivering, and sensing applications, was tuning the nanoparticle shape and the length and sequence of the DNA connectors. The engineering was guided by simulations carried out by Sharon C. Glotzer and her team at the University of Michigan (Science A colloidal clathrate crystal (shown in a close-up at left) is 2017, DOI: 10.1126/ prepared by programmable assembly of DNA-functionalized science.aal3919). triangular bipyramidal gold nanoparticles, shown without DNA The researchers in a structural model (right). prepared anisotropic, triangular bipyramidal gold nanoparticles that align into tetramers. Attaching a DNA monolayer to the gold leads to assembly of nanoparticle clusters that form the colloidal crystals with patterns that,
CREDIT: NAT U RE (MICROGRAPH); CELL CHEM. BIOL. (RIBBON); SCIENCE (CLATHRATES)
Researchers have discovered that caspases, enzymes that promote inflammation and cell death, are secondary targets for some nonsteroidal anti-inflammatory drugs (NSAIDs) (Cell Chem. Biol. 2017, DOI:
rather than become densely packed, leave polygon-shaped holes. The DNA had to be highly specialized, bearing a thiol on one end to bind to gold, single- and double-stranded segments to optimize the length and flexibility, and a four-base “sticky end” so DNA strands could connect and facilitate clathrate assemblies in solution. Jennifer N. Cha of the University of Colorado, Boulder, says, “This work will likely lead toward fabricating the next generation of unique nanoparticle architectures and expanding the scope of applications for such materials, including hostguest recognition and catalysis.”—STEVE
RITTER
ONCOLOGY
▸ Platinum-containing cancer drugs differ mechanistically Platinum-containing drugs are used to treat many types of cancer. Drugs such as carboplatin and oxaliplatin were developed to avoid some of the side effects and treatment resistance associated with traditional cisplatin. Researchers thought all these drugs kill cells by triggering a DNA-damage response. But oxaliplatin has an unusual side-effect profile and works against cancers for which other drugs, such as cisplatin, are minimally effective.
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A team led by Michael T. Hemann and Stephen J. Lippard of MIT now demonstrates that oxaliplatin works through a different mechanism (Nat. Med. 2017, DOI: 10.1038/ nm.4291). The researchers used RNA interference to target genes with known or suspected roles in cell-death signaling pathways and to see how those pathways responded to various platinum-containing drugs. They found that instead of killing cells through DNA damage, oxaliplatin induces ribosome biogenesis stress, in which cells produce large quantities of the protein-translation machinery, throwing protein production out of whack. In a bit of a vicious cycle, ribosome biogenesis stress may further sensitize cells to oxaliplatin. The findings suggest that platinum drugs don’t necessarily function inter-
ENERGY STORAGE
Tin-phosphorus anodes for potassium-ion batteries The rapidly growing lithium battery industry has spurred a high demand for lithium minerals and a subsequent concern about the limited global supply and high cost of these materials. So scientists are searching for alternatives. In terms of energy storage capacity and other electrochemical properties, potassium-ion batteries (PIBs) look more promising than sodium-ion batteries. But PIB development has been hampered by a lack of suitable anode materials, especially ones that can accommodate potassium ions’ larger size than lithium and sodium. Zhixin Chen, Zaiping Guo, and coworkers at the University of Wollongong may have come up with a solution. The team reports that a PIB anode made of an inexpensive composite of Sn4P3 and carbon exhibits high charge capacity, fast charging rates, and voltage characteristics suitable for industrial battery applications (J. Am. Chem. Soc. 2017, DOI: 10.1021/jacs.6b12185). In addition, the electrochemical profile of the material indicates that Sn4P3-carbon anodes have little risk of forming metal dendrites, which have been implicated in battery failure due to short circuiting.—MITCH
JACOBY
changeably with their derivatives, the researchers note.—CELIA ARNAUD
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ANTIBIOTICS
▸ Muting bacteria to prevent infection Researchers have developed a new infection-blocking material made of peptide-containing nanofibers that works against antibiotic-resistant bacteria and could one day be incorporated into wound dressings (ACS Infect. Dis. 2017, DOI: 10.1021/acsinfec dis.6b00173). The approach targets bacterial quorum sensing—a mode of chemical communication used by bacteria to detect other
Electrospun fibers containing a peptide that blocks bacterial quorum sensing prevent Staphylococcus aureus from activating its infectious pathways.
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O bacteria. When they sense that enough of their This peptide blocks kind are present, quorum sensing in they can mount S. aureus. an infectious attack. Chemist Helen E. Blackwell of the University of Wisconsin, Madison, has developed peptides to block this quorum-sensing pathway, thereby preventing cells from attacking their host. Together with David M. Lynn and other Wisconsin colleagues, Blackwell electrospun one of these peptides into poly(lactide-co-glycolide) nanofibers. The researchers tested nanofiber mats against normal and deadly antibiotic-resistant strains of Staphylococcus aureus. By using a strain of S. aureus engineered to carry fluorescent reporter genes, the scientists found that the fibers with quorum-sensing inhibitors were able to block the bacteria from successful quorum sensing for up to two weeks. Moreover, when cultured in petri dishes with red blood cells, the treated bacterial cells did not rupture the blood cells, whereas untreated cells did. The presence of ruptured cells indicates that bacteria are using quorum sensing to coordinate an infection.—WUDAN YAN, special to C&EN MARCH 6, 2017 | CEN.ACS.ORG | C&EN
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