George W. Gokel, Ph.D., professor of molecular biology and pharmacology and director of the Bioorganic Chemistry Program at Washington University, has received a four-year $1.1 million grant from the National Institute of General Medical Sciences. The funding will allow Gokel to study the properties of synthetic ion channels.
Ion channels occur in all living organisms, serving as selective gateways through the outer membrane of cells. For example, some channels allow potassium ions to flow through the barrier between a cell's surroundings and its interior to maintain the balance between sodium and potassium. But such channels are difficult to study because they are large and assembled from protein building blocks. Therefore, little is known about how they attract ions at one face of a membrane and release them at the other.
Gokel has received international recognition for his work on macrocyclic compounds -- ring-shaped molecules made of nine or more carbon atoms. By attaching side chains to such compounds, he has produced molecules that insert themselves into membranes and interact with small positively charged ions. These molecules therefore can serve as models of ion channels. "We have developed a system that is shorn of biological complexity but functions well enough to throw light on the chemical interactions that must occur when ions pass through protein channels," Gokel said.
His long-term goal is to synthesize more complex ion channels for therapeutic use. "One idea is to develop a channel that could selectively insert itself into the outer membrane of disease-causing fungi," he said. "By disturbing the ion balance of the cells, the channel could serve as a new type of anti-fungal agent."
