Navigation Links
OSU chemist developing solution to nerve agent exposure
Date:4/5/2011

Scientists are working to develop a new drug that will regenerate a critical enzyme in the human body that "ages" after a person is exposed to deadly chemical warfare agents.

Christopher Hadad, Ph.D., professor of chemistry at The Ohio State University (OSU), is leveraging Ohio Supercomputer Center (OSC) resources to help develop a more effective antidote to lethal chemicals called organophosphorus (OP) nerve agents.

"This project is a combination of synthetic and computational organic chemistry conducted through OSC at Ohio State, and biochemical studies conducted by colleagues at the U.S. Army Medical Research Institute of Chemical Defense at Aberdeen Proving Ground in Maryland," said Hadad.

OP nerve agents inhibit the ability of an enzyme called acetylcholinesterase (AChE) to turn off the messages being delivered by acetylcholine (ACh), a neurotransmitter, to activate various muscles, glands and organs throughout the body. After exposure to OP agents, AChE undergoes a series of reactions, culminating in an "aging" process that inhibits AChE from performing its critical biological function. Without the application of an effective antidote, neurosynaptic communication continues unabated, resulting in uncontrolled secretions from the mouth, eyes and nose, as well as severe muscle spasms, which, if untreated, result in death.

Conventional antidotes to OP nerve agents block the activity of the nerve agent by introducing oxime compounds, which have been the focus of a number of studies. These compounds attach to the phosphorus atom of the nerve agent, after the OP is bound to AChE, and then split it away from the AChE enzyme, allowing the AChE to engage with receptors and finally relax the tissues.

However, in some cases, the combined nerve agent/AChE molecule undergo a process called aging, in which groups of single-bonded carbon and hydrogen atoms called alkyl groups are removed from the molecule and a phosphonate residue is left behind in the AChE active site. Relatively unstudied in nerve agents, this process, called dealkylation, makes the nerve agent/AChE molecule unreceptive to oximes an unfortunate situation, considering that certain nerve agents (e.g., soman) can undergo aging within minutes of exposure to AChE.

Hadad's study is focused on the identification of compounds that would return an appropriate alkyl group to the aged nerve agent/AChE molecule, thus allowing treatment with oximes to provide for complete recovery. The project is investigating common OP nerve agents Tabun, VX, VR, Sarin, Soman, Cyclosarin and Paraoxon, all of which take on a similar molecular structure upon aging.

"Computational studies of the interaction of the alkylating compounds with AChE were used to provide insight for the design of selective reagents," Hadad explained. "Ligand-receptor docking, followed by molecular dynamics simulations of the interactions of alkylating compounds with aged OP-AChE, was carried out in conjunction with experimental studies to investigate the binding of alkylating compounds to AChE. These results were then used to suggest interactions that aided in the orientation of alkylating compounds for maximal efficacy."

Throughout the project, Hadad employed computational studies to guide the progress of each objective, as well as to rationalize the observed experimental results.

"Dr. Hadad's work on this project has made use of a range of the tools of electronic structure theory, molecular docking, molecular dynamics and hybrid quantum mechanical/molecular mechanical methods," said Ashok Krishnamurthy, interim co-executive director of OSC. "It was by design that OSC's flagship system, the Glenn IBM 1350 Opteron cluster, was developed to meet the needs of the bioscience research investigators, such as Dr. Hadad."


'/>"/>

Contact: Jamie Abel
jabel@osc.edu
614-292-6495
Ohio Supercomputer Center
Source:Eurekalert  

Related biology news :

1. UC Riverside biochemists devise method for bypassing aluminum toxicity effects in plants
2. Research center to free chemistry from Earths bonds
3. Vitamin D a key player in overall health of several body organs, says UC Riverside biochemist
4. Volcanoes may have provided sparks and chemistry for first life
5. The Camille & Henry Dreyfus Foundation to host important symposium on chemistry and the environment
6. JHU chemists devise self-assembling organic wires
7. Biochemistry of human physiology in health and disease is focus of updated clinical text
8. Chemist to donate potential pharmaceutical royalties to Madagascar
9. Brown chemist finds gray molds killer gene
10. International public-private partnership offers new paradigm for medicinal chemistry
11. Chemistry professor 1 of only 3 at UH to achieve prestigious AAAS status
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
OSU chemist developing solution to nerve agent exposure
(Date:1/20/2016)...   MedNet Solutions , an innovative SaaS-based eClinical ... research, is pleased to announce the attainment of record-setting ... result of the company,s laser focus on (and growing ... it,s comprehensive, easy-to-use and highly affordable cloud-based technology platform. ... MedNet growth achievements in 2015 include: , ...
(Date:1/15/2016)... JUAN, Puerto Rico , Jan. 15, 2016 /PRNewswire/ ... companies big and small to find new ways to ... driven culture. iOS and Android ... device based on biometrics, transforming it into a hardware ... request that users swipe their fingerprint on their KodeKey ...
(Date:1/11/2016)... , Jan. 11, 2016 Synaptics Incorporated ... interface solutions, today announced that its ClearPad ® ... (TDDI) products won two separate categories in the 8 ... Innovator and Best Technology Breakthrough. The Synaptics ® ... a simplified supply chain, thinner devices, brighter displays and ...
Breaking Biology News(10 mins):
(Date:2/9/2016)... ... February 08, 2016 , ... ... services, announced today the launch of its revamped and improved website. In an ... service solutions, the redesigned website will better communicate how the company designs and ...
(Date:2/9/2016)... ... February 09, 2016 , ... The publishing industry has ... publishing is one of the popular publication models that has received wider acknowledgement ... and 3000+ International Conferences across the globe, OMICS International is all ...
(Date:2/9/2016)... LONDON , February 9, 2016 ... replace paper and protect IP   E-WorkBook ... will be rolled out in Germany ... and protect valuable IP. Users will be able to search ... or experiment as part of the application, to boost collaboration ...
(Date:2/8/2016)... , Feb. 8, 2016 /PRNewswire/ - BIOREM Inc. (TSXV: BRM) ... top ten finalists for clean technology companies in the TSX ... top 10 companies listed on the TSX Venture Exchange, in ... gas, clean technology & life sciences, diversified industries ... weighting given to return on investment, market cap growth, trading ...
Breaking Biology Technology: