The hCEI-trimer that Hemmert and Redinbo developed while answering their question: "What if the enzyme could be changed so that it breaks down chemical warfare nerve agents"
Matt Redinbo, Ph.D., calls his mentoring of doctoral student Andy Hemmert “a really collaborative relationship.”
Hemmert and Redinbo engineered the protein human carboxylesterase 1 (hCE1) into an enzyme capable of hydrolyzing organophosphate nerve agents using x-ray crystallography, bioinformatics, molecular biology and biochemical techniques.
Organophosphate (OP) nerve agents and their chemical structures.
Former post-doctoral fellow Andy Hemmert altered the structure of an enzyme so that it will destroy all known nerve agents used in chemical warfare. Now the U.S. Army is testing it.
Combating chemical warfare with a catch-all antidote
Someday, a bio-scavenger may be a soldier’s best friend.
In chemical warfare, nerve agents inhibit an enzyme that is crucial for muscle control. If the enzyme is poisoned, the diaphragm won’t move, so the victim suffocates.
As a UNC doctoral student, Andy Hemmert set out to alter a similar enzyme into a bio-scavenger that would destroy all known nerve agents before they could do harm.When Hemmert arrived at Carolina five years ago, a previous graduate student had just deciphered the structure of an enzyme in the liver that breaks down toxins.
“What should we do with it?” was the question that Matt Redinbo
, Ph.D., chemistry department chair, posed to the new doctoral candidate.
What if, they asked, that enzyme could be changed so it would break down chemical warfare nerve agents? Hemmert went to work.
“He did the work in the lab and would bring the data to me for feedback and suggestions on what to do next,” says Redinbo. “It became a really collaborative relationship.”
The U.S. military equips soldiers with treatments to neutralize some of the agents. They save lives but cause sickness and long-term side effects. Antidotes for all agents exist, but technologies to distinguish among agents – so that one knows which antidote to take – are too expensive and cumbersome to carry in the field.
Hemmert, a biochemist based in the School of Medicine, set out to find a one-antidote-fits-all – a sort of bioscavenger. Of 560 potential changes to the enzyme, Hemmert found 50 that do the trick. Only nerve agent analogs – not the real thing – are used in UNC labs.
Their lead antidote candidate will be tested at the U.S. Army Medical Research Institute of Chemical Defense. The goal is to find out if an injectable version of the antidote will have few side effects and last several days in the bloodstream.
The ultimate goal? For soldiers and first responders to take the antidote before going into a situation in which they may face a chemical attack.
Meanwhile, Hemmert, Redinbo and graduate student Jonathan Edwards created a company, Identizyme Defense Technologies, to further the work. Funded by a $70,000 grant from the Army, Identizyme is renting space at UNC. Hemmert has been lured away by a job offer, but Redinbo and Edwards will keep Identizyme thriving.
Another Identizyme project could help soldiers before the catch-all antidote is ready: creating a decoder about the size of a credit card that would show color patterns depending on which nerve agents were present. A color key would tell soldiers and first responders which antidotes to take.
“That was one of the best experiences offered at Carolina,” Hemmert says. “I don’t think that anywhere else I would have had the same opportunity.”