Nerve agent decontamination compounds

Novel enzymes with highly tailored capability to degrade toxins

Medical & Biotechnology Military Technology

Photo by Staff Sgt. Brian Barbour, Arizona National Guard Public Affairs

VX ((Ethyl {2-[bis(propan-2-yl)amino]ethyl}sulfanyl) (methyl)phosphinate is one of the most toxic compounds known in humans and is categorized as a weapon of mass destruction. The median lethal dose (LD50) for humans is estimated to be about 10 milligrams when contact is through the skin. The estimated LCt50 for inhalation is estimated to be 30-50 mg·min/m3. VX was the weapon used against Kim Jong-nam, half-brother of North Korean leader Kim Jong-un, in 2017.

No efficient and easily produced catalyst for VX degradation in the environment or in vivo is known. One enzyme, phosphotriesterase (PTE), also known as organophosphorus hydrolase (OPH), has previously been reported to possess VX activity. However, PTE is not easily produced in bacteria at high concentrations necessitating more complex synthesis procedures and increasing the difficulty of obtaining sufficient, active quantities of the enzyme to be useful in an environmental setting.

To combat the threat posed by a VX release, Army researchers have developed a composition for its catalytic degradation.

The scientists discovered that the enzyme organophosphorus acid anhydrolase (OPAA), which in wild-type form is unable to catalyze the degradation of VX, can be mutated to alter its substrate specificity to act on VX causing its degradation. One particular mutation, Y212F, whereby a tyrosine is replaced by a phenylalanine at position 212, catalyzes the degradation of VX with an excellent specific activity. This allows mutant OPAA enzymes to be used for in vivo treatment of VX poisoning or for the catalytic decontamination of VX from surfaces or in the environment.

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