NEWS OF THE WEEK
TOM CAMPBELL/PURDUE UNIVERSITY
GROUP BLAMES PESTICIDE FOR MICROCEPHALY
Mosquito larvae develop in water before emerging as adults.
But Brazil’s Ministry of Health says that “no epidemiological studies show the association between use of pyriproxyfen and microcephaly.” On the other hand, tests of blood, tissue, and amniotic fluid from affected infants suggest a relationship between Zika and microcephaly, according to the ministry. Some localities that do not use pyriproxyfen also have reported microZIKA VIRUS: Experts dismiss cephaly cases, the ministry adds. connection between pyriproxyfen Sumitomo asserts that the chemical, which it disand epidemic among newborns covered in 1984, is safe and that “concerns related to microcephaly are totally unfounded.” The product is approved in 40 countries and recommended by the N ARGENTINIAN physicians group claims that World Health Organization as safe for use in drinking a larvicide, not Zika virus, is responsible for an water, Sumitomo says. outbreak of infants born with small heads in Pyriproxyfen works by interfering with mosquitoes’ Brazil. While some local governments in Brazil have growth hormones “from hatching, to N stopped using the larvicide, pyriproxyfen, government larvae, to pupae,” explains Ian Musauthorities and scientific experts contend that it is safe. grave, a pharmacology lecturer at the O Pyriproxyfen is used to treat drinkUniversity of Adelaide. The hormonal O ing water, where it kills off the larvae pathway of the growth regulator, so effecof mosquitoes, including those retive against mosquitoes, “does not exist in O sponsible for transmitting Zika virus. organisms with backbones, such as humans,” Over the past year, Brazilian authorities he says. “Pyriproxyfen has very low toxicity in Pyriproxyfen have counted more than 4,000 cases of micromammals as a result.” cephaly, as the affliction in newborns is known, in areas Some scientists wonder whether an unknown agent where Zika virus is now widespread. is responsible for the microcephaly. “Perhaps they A report from Physicians in the Crop-Sprayed Vilare getting a new chemical that forms on reaction of lages insists that marketing efforts by the chemical’s pyriproxyfen with whatever reagent they use for water maker, Sumitomo Chemical, and government indifferpurification,” suggests Susan Kegley, CEO of the conence to the mostly poor population affected by microsulting firm Pesticide Research Institute. “There is cercephaly are responsible for the tragedy. tainly more than one possibility.”—MARC REISCH
A
DNA ENZYMES SNIP AMIDE BONDS
H2O DNA
O N H
⨉
O ⨉ = HN
O
⨉
OH N
⨉ ⨉ ⨉ ⨉
⨉
BIOCATALYSIS: Amide hydrolysis
is first step on the way to DNAbased protein cleavage
C
HEMISTS AT THE University of Illinois, Urba-
na-Champaign, have identified a deoxyribozyme that catalyzes amide hydrolysis, the first step toward making a DNA-based enzyme that can cleave proteins in specific places. Such a DNA enzyme could help researchers process proteins for proteomic studies. Scott K. Silverman and his team have been trying unsuccessfully to find an amide-hydrolyzing deoxyribozyme for years. Their first attempt yielded DNA 3´ a DNA that performed phosphodiester 5´ cleavage instead. “There’s something about an amide bond that is difficult to cleave—at least by a nucleic acid catalyst,” Silverman says. Now, Silverman’s team has managed to produce DNA sequences that cleave amide bonds by incorporating modified nucleotides with amine, hydroxyl, or CEN.ACS.ORG
6
ADAPTED FROM J. AM. CHEM. SOC.
By replacing all thymidines in a DNA molecule with modified bases, researchers found catalysts that can hydrolyze amides. Shown here is one of the modifications: a base with a hydroxyl attached to the 5-methyl group of thymidine.
carboxyl groups (J. Am. Chem. Soc. 2016, DOI: 10.1021/ jacs.5b12647). The modifications mimic the side chains on amino acids that are involved in peptide bond cleavage by natural proteases. “There’s a mechanistic basis for expecting some benefit from including these side chains on the nucleobases,” Silverman says. But because these modified bases are still DNA, the researchers could use tools to amplify the nucleic acids, as well as methods developed for selecting and evolving DNAs for specific functions. Through these selection methods, Silverman’s team screened a library of catalysts consisting of 40-nucleotide-long random sequences flanked by regions with fixed sequences that could bind a model substrate. The substrate comprised an amide bond inserted between DNA sequences. They found multiple catalysts that enhanced the rate of amide hydrolysis by about 1,000-fold. “It’s not a blazing catalyst,” says Gerald F. Joyce, whose group studies functional nucleic acids at Scripps Research Institute, California. “But it has a nice acceleration compared to the uncatalyzed reaction.” In addition, one of the catalysts with hydroxyl-modified bases retained some activity even when resynthesized with unmodified DNA. “So the story comes full circle, and it seems that unmodified DNA can do this reaction after all,” Joyce says.—CELIA ARNAUD
FEBRUARY 22, 2016
