A group of Duke chemists are in the process of refining a new diversity-based method to serve as a starting point for drug discovery and research. The researchers, led by Eric Toone, professor of chemistry, hope to establish a facility in the Triangle to house this process.
Toone’s lab has created thousands of small molecules and entered them into a large chemical library, which can later be screened using a specialized robotic system that finds the best molecule or molecules to fit into specific protein receptor sites. This process is similar to the “lock and key” theory, by which complementary shapes on substrates and enzymes interlock.
After certain compounds are found to be a “good fit,” molecule synthesis occurs and factors such as efficacy, lifetime, toxicity and side effects are explored in order to determine the viability of the drug.
Researchers said the applications of this technology are valuable to therapeutic development and translational research, which applies basic research findings to clinical situations to develop and improve upon therapeutic methods.
“You can use it for finding drug targets in cancer, tuberculosis and heart disease, for example,” Toone said. “Basically, if there is a protein target, this methodology is appropriate.”
The benefit of the new system is its accessibility for researchers, who can consult the library to ignite their own work.
So far, this technology has only been available to Duke investigators, who have said they are pleased with its development.
“It adds another dimension to what can be done at Duke,” said Timothy Haystead, associate professor of pharmacology and cancer biology. He used the new technology in his research for designing a drug to treat cardiovascular disease.
Pat Casey, director of the Center for Chemical Biology, has already experienced success with the diversity-based method. It enabled his research team to discover a compound that inhibits the enzyme ICMT, which modifies oncogenes, or cancer-causing genes.
“Duke is great at building upon this translational initiative,” Casey said. Duke University Medical Center is developing the program internally rather than partnering with the biotechnology and pharmaceutical industries in the area.
“We hope to do as much within the University rather than outside,” said Bob Taber, vice chancellor of science and technology. “We are currently one of the largest University recipients of industry dollars, but some things are just better left under academic supervision.”
Researchers hope to expand their resource base by partnering with the University of North Carolina at Chapel Hill and North Carolina State University, but there are no plans in the works to build additional facilities.
“This kind of facility is very expensive to set up and to operate,” Toone said. “There’s no real need for more than one in the area as long as ours is up and running.”
Very few research institutions have developed this type of translational technology. This research at Duke is facilitated by a well-developed translational research initiative, which the University encourages through its research-oriented mission statement.
“Many universities do not have the access to such a key step in developing drugs,” Taber said. Others are still struggling to determine how to fit drug discovery and translational research into their institution’s mission.
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