An HIV drug dismissed for its side effects will get a second chance to prove its value, thanks in part to research, which Christian Melander and T. Eric Ballard conducted.
Melander, an assistant professor of chemistry, and Ballard, a graduate student studying synthetic and organic chemistry, worked with UNC-Chapel Hill’s microbiology department and the University of Colorado at Boulder’s chemistry departments to develop a new nanoparticle called SDC-1721.
Adapted from a particle known as TAK-779, SDC-1721 has been shown to bind with HIV particles and prevent them from fusing with healthy cells. Unlike TAK-779, SDC-1721 does not contain an ammonium salt found to cause inflammation at the site of injection.
“To synthesize SDC-1721, it was much easier to take out the ammonium salt then to try to retain it,” Ballard said. “It was a risk, since that was an active part of the molecule, but for ease of synthesis, it was deemed necessary.”
Although SDC-1721 has only been tested in a lab setting, Melander and Ballard said they are confident the new particle will not create the same side effect in animal tests. They plan those tests next, along with tests against mutant strains of HIV.
One of the keys to the research was the use of gold to prevent the particle from reacting with the wrong cells in the body.
“We’ve known about [gold] for a few thousand years,” Melander said. “It is nontoxic, and the body completely ignores it.”
Melander and Ballard were cogs in a larger machine, which spread across the three campuses.
“Everybody had a defined role,” Ballard said. “I had to figure out how to make it, the best and most efficient pathway.”
Ballard, who started working on the project in the summer of 2006, said he spent six months reviewing literature and designing the molecule.
“The particles were then attached to gold nanoparticles by Chris Ackerson in [Daniel] Feldheim’s group and tested against HIV by Mary-Catherine Bowman in [David] Margolis’ lab.”
Daniel Feldheim is a former N.C. State chemistry professor who, along with Melander, planned the scope of this project. He is currently a professor at the University of Colorado.
The team published a paper last month in the Journal of the American Chemical Society entitled “Inhibition of HIV Fusion with Multivalent Gold Nanoparticles,” and Melander said the response was positive and “significant.”
The paper is the result of two years of research and design, but Ballard said the particle was simply a “proof of concept.”
“Now that we have proved we can do it, there’s a lot more we can do,” Ballard said.
Melander said this project was the first to synthesize a new particle, but there are more being developed.
“We’re working on small molecules with biological effects,” he said. “Now we’re looking at diseases with no adequate solutions.”