Science Concentrates ANALYTICAL CHEMISTRY
▸ Possible new way to attack tuberculosis The bacterium Mycobacterium tuberculosis claimed 1.8 million lives worldwide in 2015, according to the World Health Organization, making tuberculosis the deadliest infectious disease on Earth. Scientists led by Deborah T. Hung of Broad Institute report a small molecule, called BRD4592, that inhibits one of the bacterium’s key metabolic enzymes—tryptophan synthase (Nat. Chem. Biol. 2017, DOI: 10.1038/ N nchembio.2420). BRD4592 shuts down this enzyme, NH not by binding to its active sites, F OH but by binding in the channel between the enzyme’s BRD4592 subunits. This allosteric binding prevents the enzyme from completing the cycle it uses to make tryptophan. It also blocks indole, an important intermediate en route to tryptophan, from shuttling between the enzyme’s two active sites. Hung’s team believes this is one of the most complicated allosteric inhibitors reported to date. The scientists found that mice metabolized BRD4592 too quickly to evaluate the compound’s efficacy in infected animals, but the team did determine that M. tuberculosis engineered without a tryptophan synthase enzyme were unable to establish an infection in mice. This, Hung’s team believes, makes allosteric inhibition of this enzyme an attractive strategy for fighting tuberculosis.—BETHANY HALFORD
NEUROSCIENCE
▸ Antibody disrupts blood-brain barrier Cells along the blood vessels in the brain form tight junctions to prevent toxic molecules—and often drug molecules—from entering the brain. Researchers have found an antibody that disrupts this blood-brain barrier in some people with an autoimmune disease (Sci. Transl. Med. 2017, DOI: 10.1126/scitranslmed.aai9111). The findings could lead to strategies to deliver drugs to the brain, the researchers say. Neuromyelitis optica is an autoimmune disease in which the immune system attacks a
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C&EN | CEN.ACS.ORG | JULY 10, 2017
Boltzmann and Planck constants remeasured NIST has announced more accurate measurements of the Boltzmann and Planck constants. The new values will contribute to an international effort to move away from defining basic units using physical objects and instead, starting in 2019, derive them from seven fundamental constants of nature. The kelvin, for example, is currently defined by measuring the triple point of water in a sealed glass cell. Going forward, metrologists want to define the kelvin in terms of the Boltzmann constant, which NIST researchers determined to be 1.3806410 × 10–23 J/K by meaNIST used this Kibble balance, shown suring the degree of random with two 1-kg platinum-iridium motion of electrons in a restandards (center), to measure the sistor (Metrologia 2017, DOI: Planck constant. 10.1088/1681-7575/aa7b3f ). Meanwhile, the kilogram is currently defined as the mass of a plum-sized cylinder of platinum-iridium alloy. Instead, metrologists want to define the kilogram in terms of the Planck constant. NIST scientists have now measured that constant’s value as 6.626069934 × 10–34 kg·m2/second by using a Kibble balance, formerly known as a watt balance, which balances the weight of a test object by passing a current through a coil suspended in a magnetic field (Metrologia 2017, DOI: 10.1088/1681-7575/aa7bf2).—JYLLIAN KEMSLEY
certain protein in brain cells, often leading to inflammation and damage to the optic nerve and spinal cord. Antibodies targeting this protein can get past the blood-brain barrier, so scientists wondered how they performed the feat. A team led by Richard M. Ransohoff of Biogen and Jeffrey L. Bennett of the University of Colorado School of Medicine found that another antibody in patients’ blood can bind to and activate the endothelial cells responsible for forming the barrier. The team determined that this antibody targeted glucose-regulated protein 78 (GRP78) on the cells’ surfaces. Injecting the GRP78 antibody into mice daily for seven days increased the permeability of the animals’ blood-brain barriers, allowing proteins of different sizes to leak into the brain from the blood. Disrupting the blood-brain barrier for drug delivery
is fraught with neurotoxicity issues, says William A. Banks of the University of Washington and VA Puget Sound Health Care System. But, he says, this study’s findings give scientists a new player to study to better understand the regulation of this important interface between the blood and brain.—MICHAEL TORRICE
NEUROSCIENCE
▸ Elevated serotonin linked to infant death syndrome It’s new parents’ worst nightmare: Their child dies suddenly in his or her sleep,
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