Science Concentrates CHEMICAL SENSING TOXICOLOGY
Detecting food allergens on the go
▸ How poison dart frogs avoid poisoning themselves
A single amino acid swap keeps golden poison dart frogs safe from their own toxin. 2 mg in adults—to kill more than 20,000 mice, yet their voltage-gated sodium channel membrane protein is immune to its paralytic effects. Sho-Ya Wang and Ging Kuo Wang of the University at Albany now report that a single amino acid swap can render sodium channels almost completely resistant to batrachotoxin. The researchers built off a study published last year by another research team that identified five amino acid substitutions differentiating poison dart frog and rat sodium channels. In the new study, scientists tested whether creating the five frog substitutions in the rat sodium channel, individually and in combination, conferred batrachotoxin resistance. Monitoring cells engineered to produce either normal or modified sodium channels revealed that replacing just one amino acid—asparagine with threonine at HO3SO
HO3SO
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HO HO
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position 1,584—conferred “exceptional” batrachotoxin resistance (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/pnas.1707873114). Sodium channels with substitutions at the other four locations remained sensitive to the toxin. Sho-Ya Wang says gaining a better understanding of how batrachotoxin interacts with sodium channels may help improve the design of therapeutic drugs that target the same region of the protein.—EMMA HIOLSKI
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C&EN | CEN.ACS.ORG | SEPTEMBER 11, 2017
killed people. A synthetic heparin called fondaparinux is safer and homogeneous. But people taking heparin sometimes experience uncontrolled bleeding, and although a drug called protamine can reverse the anticoagulant activity of unfractionated heparin, it does so incompletely with low-molecular-weight heparin and doesn’t reverse fondaparinux activity at all. Robert J. Linhardt of Rensselaer Polytechnic Institute, Jian Liu of the University of North Carolina, Chapel Hill, and coworkers re-
▸ Synthetic heparin could improve bloodthinning treatments A new synthetic version of the sulfated polysaccharide heparin that could be safer or have more-reversible activity than currently approved versions of the
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DRUG DEVELOPMENT
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anticoagulant has been produced in quantities that begin to approach those needed for commercialization. Three types of heparins are currently approved as blood thinners to treat clotting disorders and prevent clotting in people undergoing kidney dialysis and surgery. Unfractionated heparin and low-molecular-weight heparin, derived from pig intestines, are mixtures with batch-to-batch inconsistencies, and contaminated batches have at times
cently used chemoenzymatic synthesis to make a synthetic heparin that is less prone to contamination, more consistent, and more amenable to protamine reversal than other heparins are. But they could produce only milligram amounts. Now, a group led by Linhardt, Liu, and UNC’s Rafal Pawlinski has added a sulfate that makes the heparin easier to synthesize, boosted the activity of two key enzymes, and found a way to produce cofactors in higher yield. The
C R E D I T: ACS N A NO ( D E T ECTO R ) ; M IC H A L . R I ES E R / WI KI MED I A CO MMO N S (F RO GS )
Doctors estimate that each year more than 200,000 people in the U.S. visit hospital iEAT consists of a portable antigen extraction kit and a emergency rooms because of food allergies. key-chain detector. This number includes an estimated 90,000 cases of life-threatening anaphylaxis. The main approach doctors recommend when it comes to food allergies is simply to avoid those foods. But that can be difficult when eating at restaurants or when traveling to countries that have less-stringent food allergen labeling laws. Researchers led by Massachusetts General Hospital’s Hakho Lee and Ralph Weissleder have now developed a prototype point-of-use allergen detection system that picks up traces of peanuts, hazelnuts, wheat, milk, and egg whites in less than 10 minutes (ACS Nano 2017, DOI: 10.1021/acsnano.7b04318). The system, dubbed iEAT, requires two steps: antigen extraction followed by detection. Antigens in the food are captured with antibody-containing magnetic beads, which are subsequently labeled with other antibodies conjugated to the oxidizing agent horseradish peroxidase. A sheathed magnet collects the magnetic beads, which are then placed on the detector, where they undergo an electrochemical reaction. The major innovation, Lee notes, is the detector that fits on a key chain, which can differentiate up to eight allergens, connect to smartphones via Bluetooth, and charge wirelessly. Each disposable antigen extraction system costs about $4.00, and the detector costs $40.—BETHANY HALFORD
Scientists have wondered how golden poison dart frogs resist succumbing to the high doses of toxin they store in their skin. Certain species of Phyllobates frogs are loaded with enough batrachotoxin—up to
