Onofrio Annunziata, professor of chemistry and biochemistry at TCU, studies how to strengthen proteins and alter their behavior. His work might lead to new intravenous drug-delivery methods or new sensors to detect biological threats.

Onofrio Annunziata, professor of chemistry and biochemistry at TCU, studies how to strengthen proteins and alter their behavior. Photo by Robert W. Hart

Proteins are organic molecules often described as the building blocks of life. But this simple description, referring to their ability to form the scaffolding of tissues and organs, belies their range of abilities, including use as body-friendly carrying cases for drugs.

Annunziata specializes in dendrimers — synthetic, star-shaped molecules that can bind to and transport proteins. Dendrimers’ symmetrical nature can make the proteins to which they attach tougher and less susceptible to deterioration inside the body.

Dendrimers are engineered on the nanoscale — that’s one-billionth of a meter — and have internal cavities that can be packed with other molecules. They dissolve in water, so they are able to break down in the body and release their cargo. Dendrimers could someday be injected into the bloodstream, where they might release protein-based medicine.

Pharmaceutical companies and research labs are developing stronger proteins that can harbor smaller molecules, such as drugs, and deliver them to specific locations in the body. But to do that, drug designers first need to understand how synthetic proteins work inside the body. Annunziata’s study of dendrimer-enhanced proteins lays the foundation for those lines of inquiry.

Dendrimers come in a variety of sizes, but larger molecules are hard to make because they fall apart more easily, Annunziata said. “Ideally, you want to make a big dendrimer, because you can carry more drug molecules at the same time in the same host particle. … Can we actually assemble small dendrimers to [make] a bigger particle? So instead of having one, we have a small collection of dendrimers that would be attached to each other.”

In a research paper published in 2017 by the American Chemical Society journal Langmuir, Annunziata and Viviana Costa ’15 PhD showed how to create “nanoassemblies” by combining clusters of small dendrimers.

Annunziata’s biochemical research also improves molecular sensors, which can safeguard against poison or biological threats.

A sensor contains proteins that react in the presence of a particular chemical. For instance, a sensor might change color if it detects cholera, a bacterium that causes violent illness.

By adding salt, Annunziata found that sensors could enhance the reaction. The additional salt can help push proteins toward the surface of the sensor, which makes dangerous compounds easier to detect. “We could definitely increase the sensitivity of the instrumentation, thereby detecting chemicals at significantly lower concentrations,” he said.

Annunziata is also learning other methods of changing the behaviors of synthetic proteins by applying heat and electricity. Doing so is a measure of molecular control, he said. “We make [particles] decide which environment they want.”