reconstructed the chemical disequilibria that were present in Earth’s ocean and atmosphere starting about 4 billion years ago and during a more recent era with very different chemistry. They conclude that searching for evidence of methane and carbon dioxide as signs of these disequilibria may give us the best chance of finding extraterrestrial life. The problem with looking for oxygen in exoplanets’ atmospheres, according to Krissansen-Totton, is that it may not be very common. The biochemical processes that make oxygen are complex, and on Earth they have evolved only one time. And even if oxygen-producing organisms do exist, the molecule is so reactive that it can take a long time for a significant amount of oxygen to accumulate in a planet’s atmosphere. “On the other hand,” says Krissansen-Totton, “making methane is relatively easy in terms of biochemistry.” And, he adds, there’s evidence that organisms evolved that ability early in Earth’s history. That means astronomers may be more likely to spot it. As luck would have it, the James Webb telescope is better equipped to observe carbon dioxide and methane than oxygen.—SAM LEMONICK
DRUG DISCOVERY
▸ Anticancer protein
C R E D I T: J . PH YS . CH EM . B
that bites polymer tail is more effective Cyclizing the termini of protein drugs can improve their pharmaceutical properties modestly, and adding polymers to protein drugs can improve their ability to last a long time in the bloodstream. But anticancer protein-polymer conjugates are often too bulky to enter tumors deeply. Researchers now find that cyclization and polymer conjugation work better together than alone. Hua Lu of Peking University and coworkers cyclized a conjugate of the anticancer protein interferon and an amino acid polymer. Compared with noncyclized conjugates, the cyclized agents have longer circulation half-life, remarkably higher retention time in tumors, and deeper tumor penetration in mice (J. Am. Chem. Soc. 2017, DOI: 10.1021/jacs.7b13017). It also inhibits tumor progression and extends survival in mice bearing grafted human tumors, while minimizing liver-damaging side effects. The researchers have not confirmed those findings in people yet, but they believe that their study provides the best evidence so far that cyclizing
MODELING
Insulin falls apart without water Computer modeling suggests that water molecules play a key role in stabilizing insulin for storage in the body, according to a Two zinc cations and ten water molecules stabilize the study (J. Phys. Chem. B. 2018, DOI: 10.1021/ interior cavity of the insulin acs.jpcb.8b00453). Insulin is bioactive as a hexamer. monomer, but it is stored in the pancreas in groups of six, coordinated around two zinc cations. X-ray crystallography analysis by Biman Bagchi and colleagues at the Indian Institute of Science paired with computer simulations revealed that water molecules, about 10 on average, are also present in an interior cavity of the hexamer. So they set out to determine what function, if any, these water molecules play. The group performed atomistic molecular dynamics simulations of the hexamer, zinc cations, and water molecules. They found that three water molecules and three histidine residues coordinate to each of the cations in an octahedral arrangement. Other water molecules enter and leave the cavity, but the simulation showed that these molecules stay fixed nearly in place while inside the hexamer. The study identified an average of 15 hydrogen bond interactions between the 10 water molecules in the cavity, as well as bonds to peptide residues. The group likens the water molecules to a backbone in the hexamer. Next, the researchers simulated the hexamer and zinc cations in the absence of water molecules. That led to new interactions between the cations and peptide residues, and the hexamer cavity collapsed within picoseconds. They did not test the hexamer with other cations, such as calcium, which are seen in nature. Bagchi says this new understanding of water’s role could help explain how the hexamer breaks apart to deliver monomeric insulin. It may also help protect insulin in pharmaceuticals against aggregation, which renders it useless. In the body, the hexamer not only serves as a stable way to store insulin, but it also prevents the monomeric form from aggregating.—SAM LEMONICK
protein-polymer conjugates is a valuable therapeutic approach warranting further preclinical study.—STU BORMAN
DIAGNOSTICS
▸ Detecting Ebola immunity with a paper test To help combat deadly outbreaks of Ebola, health care workers need a simple, portable test to determine immune response to the disease. Now, researchers have developed a colorchanging, paper-based strip that detects antibodies against the virus in blood serum (ACS Nano 2018, DOI: 10.1021/ acsnano.7b07021). Molly M. Stevens of Imperial College London and colleagues
printed lines containing three antigens produced by different subtypes of the Ebola virus on one end of a commercially available paper test strip. To use the paper device, the team delivers a drop of blood serum to the other end of the strip and follows it with a solution of antibodies that label the target Ebola antibodies with gold nanoparticles. As the fluids wick past the test lines, Ebola antibodies in the serum bind to the nanoparticles and then to the antigens, causing the test lines to turn reddish purple within 15 minutes. A smartphone app measures the intensity of the line colors to give a positive or negative result. Compared with results from the gold standard lab-based assay, the test was 100% accurate at detecting individuals who had survived Ebola and gave one false positive with an uninfected sample.—PRACHI PATEL, special to C&EN JANUARY 29, 2018 | CEN.ACS.ORG | C&EN
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