Civilians and military troops alike are exposed to toxic agents in the forms of pesticides and chemical weapons – chemicals that can cause brain damage. Now, researchers are advancing the stability of a protein that can counteract these poisonous chemicals, potentially preventing brain damage.
The research was led by Prof. Jin Kim Montclare and Richard Bonneau, of New York University, and is published in the journal ChemBioChem. The study focuses on detoxifying organophosphates – compounds frequently used in pesticides and the sarin gas used in warfare devices.
The team looked at proteins known as phosphotriesterases, which are able to degrade the toxic chemicals used in industry and war. They explain that organophosphates bond to neurotransmitters in the brain, which interferes with their ability to work properly, causing permanent damage.
Previous studies have shown that even low-level exposure to organophosphates damages the brain and nervous system. In a 2012 study, Dr. Mackenzie Ross, of the University College London in the UK, noted that the majority of studies from the past 20 years show a significant link between even low-level exposure to the chemicals and impaired cognitive function.
“Organophosphates pose tremendous danger to people and wildlife,” says Prof. Montclare in this latest study, “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.”
She adds that they have known phosphotriesterases are able to detoxify these compounds, but until now, “they were far too fragile to be used therapeutically.”
Specifically, these proteins were limited by their short half-lives and their instability at high temperatures. But the team created a method to re-engineer them by assimilating an artificial fluorinated amino acid and computational biology.
To do this, Prof. Montclare and her team used Rosetta computational modeling software to find sequences in the fluorinated phosphotriesterase protein that could be altered to increase the proteins and make them therapeutically viable.
Their new method produced a thermo-stable protein with a longer half-life. What this means is that they have created a more stable version of the protein with the same detoxification abilities of the original, unstable version.
As such, Prof. Montclare says this re-engineered protein could be used to prevent nerve damage in the wake of a gas attack or exposure to pesticides, adding:
”Oftentimes, chemical agent stockpiles are decommissioned through processes that involve treatment with heat and caustic chemical reagents for neutralization, followed by hazardous materials disposal. These proteins could accomplish that same task enzymatically, without the need for reactors and formation of dangerous byproducts.”
The team, whose process is patent-pending, plans to begin development of therapeutic uses for this modified protein.