Colorado State University professor to develop proteins that could be basis for new cancer and HIV treatments

Brian McNaughton, a professor of chemistry, biochemistry and molecular biology at Colorado State University, has received a $1.5 million grant from the National Institutes of Health to develop synthetic proteins that shut down disease-causing components in cells that do not respond well to traditional drug treatments. This research into novel proteins has the potential of eventually developing new treatments for cancers or HIV.

These proteins are biologics, a relatively new sector of the global pharmaceutical and biotechnology industries. Biologics, such as the designer proteins developed by McNaughton’s lab, are substantially larger and more complex than conventional drugs.

“For decades, the global pharmaceutical industry has relied on small organic molecules as drugs. While these reagents continue to dramatically improve human health, their fundamental limitation is encoded in their name,” McNaughton said. “The molecules are too small to act on the majority of disease-causing components in a cell. Our approach is to literally go bigger and generate synthetic proteins capable of suppressing the disease-causing activity of these components.”

McNaughton and his team will use a technique that relies on a green fluorescent protein originally isolated from a luminescent Pacific jellyfish. The team has recently developed a technique called “split-superpositive green fluorescent protein reassembly”.

Using this technology, researchers in the McNaughton lab will screen a billion different proteins in E. coli to identify the relatively few that recognize a disease-causing agent and bind to it tightly. When binding occurs the two halves of the split-superpositive green fluorescent protein fragments assemble, and that particular E. coli cell turns bright green.

“When an E. coli cell turns fluorescent green, we know there is a potential protein drug lead inside. We isolate that green E. coli from the other cells and identify what the sequence of this new protein is. We then characterize it to see how good of a drug lead it is,” McNaughton said.

Most of the pharmaceutical drugs on the market today are still small molecule drugs.
In recent years, however, biologics, which include protein-based drugs, have emerged as important players in the war on disease. Eight of the top-selling 20 drugs in 2013 were biologics, according to data compiled by Genetic Engineering and Biotechnology News.

McNaughton said there is still much research to be done on protein-based therapeutics, which is why the NIH is funding projects like his.

“Protein-based therapeutics are very promising, but there are still a significant number of hurdles that must be overcome to fully realize their potential,” he said. “It’s too early to tell if protein drug leads developed in our lab will make it to the clinic. However, we’re excited to be involved in exploring the potential of this therapeutic approach.”