The use of Solid-State NMR spectroscopy to investigate the structure and function of membrane proteins represents an important new opportunity in the research and development of drugs to treat influenza and tuberculosis.
In a recent interview, NMR expert Dr Tim Cross explained how his research team have been using the technique to investigate membrane proteins as potential targets in preventing the diseases. Dr Cross is Director of the NMR and MRI programs at the National High Magnetic Field Laboratory, Florida State University, where his team have made exciting new discoveries about the role tuberculosis and influenza membrane proteins play in disease processes. The researchers also found that inhibition of these proteins may offer a lead in the development of more effective pharmaceuticals.
One example of a protein Dr Cross and colleagues have been studying is the M2 proton channel, which is present in the influenza viral coat and allows protons to flow into the virus. The researchers found that interrupting this proton flow can prevent or stall infection and the team is currently in the process of developing new agents that will inhibit the M2 proton channel. This represents a particularly exciting opportunity for the pharmaceutical industry, considering that during the swine flu epidemic, a mutation in this virus rendered two of the four currently available treatments ineffective. An urgent need therefore exists for the development of new drugs to treat the illness.
Another project the team are working on focuses on the mechanism by which cell division occurs in mycobacterium tuberculosis infection. By understanding the proteins present in the bacterial divisome (the group of proteins involved in cell division), the researchers hope to find ways to prevent bacterial cell division and therefore halt disease progression. Recently, the researchers have characterized the 3-D structure of a key protein called CRGA, which recruits other divisome proteins to the site of cell division. They have also started investigating several of the proteins that bind to CRGA, as well as how to inhibit the activity of these proteins as they form a cluster.
Tuberculosis currently kills 1.3 million people a year and the agents people need to take for drug-resistant tuberculosis are particularly toxic, causing side effects that kill a large proportion of those infected. The development of molecular inhibitors that will block divisome proteins therefore represents another extremely exciting opportunity in the development of pharmaceuticals that may be able to combat the infection.
Dr Cross explains how high quality, state-of-the-art technology is at the heart of the team’s success. Without the use of sophisticated instrumentation, it would not have been possible to get the electric fields out of the sample and to open up this whole new field of study. Now, the scientists are hoping to push their research even further by using technology that involves higher magnetic fields and enables the characterization of larger molecular weight proteins.