Scientists are developing a way to prevent brain damage among people exposed to poisonous chemicals found in pesticides and chemical weapons.
The work, published in the journal ChemBioChem, centers on proteins called phosphotriesterases, which degrade chemicals in a class known as organophosphates.
Organophosphates are found in everything from industrial pesticides to the sarin gas used in chemical warfare. They permanently bond to neurotransmitters in the brain, interfering with their ability to function and causing irreversible damage.
The detoxifying ability of phosphotriesterases has been documented before, but until now their use has been limited by a short half-life and instability at high temperatures.
The new method of re-engineering phosphotriesterases incorporates an artificial fluorinated amino acid. The result is a thermo-stable protein with a longer half-life that retains all the detoxification capabilities.
“Organophosphates pose tremendous danger to people and wildlife, and sadly it’s not unusual for humans to come into contact with these compounds, whether through exposure to pesticide or an intentional chemical warfare attack,” explains Jin Kim Montclare, associate professor of chemical and biological engineering at the New York University School of Engineering.
“We’ve known that phosphotriesterases had the power to detoxify these nerve agents, but they were far too fragile to be used therapeutically,” she says.
NERVE AGENT STOCKPILES
The possibilities for this reengineered protein are considerable. Montclare explains that in addition to therapeutic formulations, which could prevent nerve damage in the event of a gas attack or pesticide exposure and would likely be developed first for military use, these proteins also could be critical when stores of toxic nerve agents need to be decommissioned.
“Oftentimes, chemical agent stockpiles are decommissioned through processes that involve treatment with heat and caustic chemical reagents for neutralization, followed by hazardous materials disposal,” she says.
“These proteins could accomplish that same task enzymatically, without the need for reactors and formation of dangerous byproducts.”
Montclare and Richard Bonneau, an associate professor in NYU’s biology department, have patented the process. Plans are under way to begin developing therapeutic applications.
Michelle Zhang, a coauthor of the paper and, at the time, a high school intern in Bonneau’s lab, first broached the idea. Zhang is now a student at Cornell University.
The US Army Research Office and the National Science Foundation supported the research.
Improved Stability and Half-Life of Fluorinated Phosphotriesterase Using Rosetta, Published on Journal 《ChemBioChem》in Jul 25, 2014.