USU Chemist Awarded Patent Toward Connexin Hemichannel Inhibitor Development

Gap-junction, what’s your function?

At northern Utah’s Golden Spike National Historical Park, about 50 miles west of Utah State University’s Logan campus, people recently gathered to celebrate the 156th anniversary of the United States’ first transcontinental railroad. The event commemorated the joining of the Union Pacific and Central Pacific railroads in 1869, achieved after six years of manual labor and secured with a ceremonial golden spike, that allowed uninterrupted rail connection of the nation’s east and west coasts.

The physical connection between the two railroads, to enable the passage of trains with passengers, news and freight, is a concept not unlike connexin hemichannels (HCs) from adjacent cells in the human body. These passages form gap-junction channels to enable cell-to-cell communication and transfer of biomolecules.

“Connexin hemichannels, a family of proteins located at the plasma membrane, along with the gap-junction channels they form, are essential for healthy cell growth, healing and organ function throughout the body,” says Utah State University chemist Cheng-Wei “Tom” Chang.

But the tube-like channels can go awry.

“Much like a tube in a bicycle tire can spring a leak, abnormal connexin hemichannels, undocked at the plasma membrane, become over-active, causing excessive leakage of biomolecules, which promotes cell damage,” says Chang, professor in USU’s Department of Chemistry and Biochemistry.

Cell damage caused by connexin hemichannels dysfunction, he says, contributes to cardiovascular disease, including heart attacks and strokes, as well as hearing loss, kidney disease, neurodegenerative diseases and other ailments.

Chang and colleague Guillermo Altenberg of Texas Tech University were awarded a patent April 29, 2025, for a method to advance development of a therapeutic agent to minimize damage from abnormal connexin hemichannel activity.

“We developed a method of synthesizing and characterizing novel molecules to inhibit connexin hemichannel dysfunction, that addresses problems experienced with previously developed inhibitors,” Chang says.

The idea of developing inhibitors to quell unchecked HC activity is relatively new – initiated within the past 10-12 years.

“A variety of inhibitors have been investigated, but they pose obstacles,” Chang says.

For example, aminoglycosides have been identified as HC inhibitors, but their antibiotic properties render them toxic to mammalian cells.

Chang and Altenberg have synthesized and tested several amphiphilic aminoglycosides, from their parent compound kanamycin A, without antibiotic effects.

“These synthesized aminoglycosides show great promise as effective hemichannel inhibitors,” Chang says. “The next step is to test these inhibitors in animal models.”