NYU researchers advance the stability of a protein that neutralizes toxins in common pesticides and chemical weapons
Research at New York University is paving the way for a breakthrough that may prevent brain damage in civilians and military troops exposed to poisonous chemicals—particularly those in pesticides and chemical weapons.
An article in the current issue of the journal ChemBioChem outlines the advancement in detoxifying organophosphates, which are compounds commonly used in pesticides and warfare agents. The patent-pending process was developed by NYU School of Engineering Associate Professor of Chemical and Biological Engineering Jin Kim Montclare, along with Richard Bonneau, an associate professor in NYU's Department of Biology and a member of the computer science faculty at NYU's Courant Institute of Mathematical Sciences.
Their work centers on proteins called phosphotriesterases, which have the unique capability of degrading chemicals in a class known as organophosphates, which are found in everything from industrial pesticides to the sarin gas used in chemical warfare.
Organophosphates permanently bond to neurotransmitters in the brain, interfering with their ability to function and causing irreversible damage. The ability of phosphotriesterases to detoxify organophosphates has been previously documented; however, applications using the protein for this purpose have been limited by its short half-life and instability at high temperatures.
Montclare and her colleagues devised a method of re-engineering phosphotriesterases by incorporating an artificial fluorinated amino acid and computational biology. The result: a thermo-stable protein with a longer half-life that retains all the detoxification capabilities of the original version.
"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," explained Montclare. "We've known that phosphotriesterases had the power to detoxify these nerve agents, but they were far too fragile to be used therapeutically," she said.
In a process that married computational biology and experimentation, the collaborators used Rosetta computational modeling software to identify sequences in the fluorinated phosphotriesterase protein that could be modified to increase its stability and make therapeutic applications a reality.
The possibilities for this reengineered protein are considerable. Montclare explained 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, the proteins 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 said. "These proteins could accomplish that same task enzymatically, without the need for reactors and formation of dangerous byproducts."
Plans are under way to begin developing therapeutic applications for this modified phosphotriesterase, and the research team believes that its methodology—using computational biology to identify potentially beneficial modifications to proteins—could point the way to future breakthroughs in engineered proteins.
The initial idea for this work was broached by Michelle Zhang, a co-author of the paper and, at the time, a high school intern in Bonneau's lab. Zhang is now a student at Cornell University. Other collaborators include NYU School of Engineering doctoral students Andrew J. Olsen, Ching-Yao Yang, and Carlo Yuvienco; and P. Douglas Renfrew, a postdoctoral scholar in the Bonneau Laboratory at NYU.
Research was supported by a grant from the U.S. Army Research Office and the National Science Foundation. The full paper, Improved Stability and Half-life of Fluorinated Phosphotriesterase Using Rosetta, is available at http://onlinelibrary.wiley.com/doi/10.1002/cbic.201402062/full.
The NYU Polytechnic School of Engineering dates to 1854, when the NYU School of Civil Engineering and Architecture as well as the Brooklyn Collegiate and Polytechnic Institute (widely known as Brooklyn Poly) were founded. Their successor institutions merged in January 2014 to create a comprehensive school of education and research in engineering and applied sciences, rooted in a tradition of invention, innovation and entrepreneurship. In addition to programs at its main campus in downtown Brooklyn, it is closely connected to engineering programs in NYU Abu Dhabi and NYU Shanghai, and it operates business incubators in downtown Manhattan and Brooklyn. For more information, visit http://engineering.nyu.edu.
Kathleen Hamilton | Eurek Alert!
New switch decides between genome repair and death of cells
27.09.2016 | University of Cologne - Universität zu Köln
A blue stoplight to prevent runaway photosynthesis
27.09.2016 | National Institute for Basic Biology
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...
Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.
Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...
The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...
With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.
Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...
For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.
Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...
28.09.2016 | Event News
27.09.2016 | Event News
23.09.2016 | Event News
28.09.2016 | Medical Engineering
28.09.2016 | Materials Sciences
28.09.2016 | Business and Finance