NEWS OF THE W EEK
IMPROVING DRUG MULTIPLICITY
NAT. COMMUN.
Molecular model of DNA-PNA fragment bound to three integrin receptors (gray). DNA fragment is dark blue; PNA, light blue; and ligands, fuchsia.
MEDICINAL CHEMISTRY: Complexes with densely arrayed bioactive groups show improved anticancer activity
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UCLEIC-ACID-BASED complexes that allow
multiple copies of a bioactive chemical group to act together to potently inhibit biological targets have now been improved and found to be effective in animals. The work could lead to drugs for cancer and other diseases that use the power of multiplicity, or multivalency, to improve on conventional one-at-a-time, or univalent, medications. Several research groups have recently added short peptide nucleic acids (PNAs), each bearing a bioactive ligand, to long single DNA strands to make DNA-PNA complexes that act as multivalent drugs, and they have tested the complexes in live cells. Now, in Nature Communications (DOI: 10.1038/ ncomms1629), synthetic organic chemist Daniel
LANZATECH BUYS RANGE FUELS FACILITY CLEANTECH: New owner will bring
its approach to making biofuels
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EW ZEALAND-BASED biofuels start-up Lanza
LANZATECH
LanzaTech is the new owner of this biofuel plant in Soperton, Ga.
Tech purchased a facility in Soperton, Ga.—previously owned by Range Fuels—at auction on Jan. 3 for $5.1 million. Range built the biomass gasification plant with the intention of making ethanol from wood chips, but the firm was unable to make the biofuel. Range’s lender took control of the facility for nonpayment and held the auction to recoup some of a $38 million loan, which had been guaranteed by the Department of Agriculture. Range was also awarded a $43 million grant from the Department of Energy. LanzaTech will evaluate the equipment at the Soperton site before it decides how it will use the property, says Freya Burton, the firm’s head of external relations. “We are planning to leave up some of the plant’s technolWWW.CEN-ONLIN E .ORG
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H. Appella of NIH’s National Institute of Diabetes & Digestive & Kidney Diseases and coworkers have created revised DNA-PNAs with multiple ligands per PNA. The complexes provide greater control than before over ligand number and density in DNA-PNAs, easing the way to determining which ones improve most on univalent drugs. As ligands, they used analogs of Merck Serono’s univalent drug cilengitide, which is currently in Phase III trials for glioblastoma and Phase II trials for other cancers. Cilengitide helps prevent cancer metastasis by blocking integrin receptors on cancer cells. Appella and coworkers added different numbers of a cilengitide analog to PNAs and then used the ligand-PNAs to create DNA-PNAs having one to 45 total ligands. In living melanoma cells and in mice given melanoma, multivalent DNA-PNAs with three ligands per PNA and 15 total ligands improved most on the antimelanoma activity of cilengitide, by about two orders of magnitude. Oliver Seitz of Humboldt University, in Germany, a DNA-PNA pioneer, comments that Appella and coworkers “have pushed the field a significant step forward to applications. They are, to my best knowledge, the first to show that DNA-programmed multivalent display works in live animals. This is a major breakthrough that can move to the field of medicine.”—STU BORMAN
ogy—potentially the gasifier. If it works, that would be fantastic,” Burton says. If the gasifier does not work, she adds, the plant is still a good buy. “We got the facility for its location and access to cheap feedstocks from local timber operations.” The technologies from both LanzaTech and Range Fuels are geared to produce ethanol from biomassderived synthesis gas. The two privately held firms also share a venture capital investor: famed clean technology backer Vinod Khosla. Range planned to use catalysts to convert the woodderived gas into ethanol. In contrast, LanzaTech’s process uses proprietary microbes to transform the gas to ethanol. In addition to ethanol, LanzaTech’s microbes produce 2,3-butanediol as a coproduct, Burton reports. Both products can be formulated into jet fuel with help from LanzaTech’s partner firms. The bargain price of the facility—and LanzaTech’s unique microbe—makes the move low risk, says Andrew Soare, clean technology analyst for Lux Research. “It could demonstrate that LanzaTech can go from gas to fuel, whereas other firms with gasification are having trouble getting all the way to ethanol.” The Soperton site, already renamed Freedom Pines Biorefinery, will be LanzaTech’s first production facility. The firm is currently working to launch a demonstration facility in Shanghai that will use waste gases from a steel mill operated by China’s Shougang Group to produce biofuels.—MELODY BOMGARDNER
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