Summary:

RNA-protein interactions are vital to the reproduction and growth of bacteria, and many antibiotics treat bacteria by inhibiting these interactions by site-specific binding to RNA. We have developed novel derivatives of a known class of antibiotics that have the capability of inhibiting protein binding to target RNA molecules while also mediating destruction of the target by catalytic hydrolysis. These new derivatives have potential applications as a new class of therapeutic agents.

We have demonstrated that the derivative antibiotics are able to catalytically cleave viral RNA at picomolar concentrations in the presence of an oxidizing agent at physiological pH and temperature. In comparison with currently available antibiotics, these compounds show similar activity against both normal and resistant bacteria and furthermore, have shown in vivo inhibition of a DNA phage virus.

Efforts are underway to develop a method which would assay the in vivo interaction between these antibiotics and RNA in order to monitor binding and inhibition of viral replication elements by these derivatives, such as the rev response element (RRE) of the HIV virus.

Potential Applications:

Treatment of bacterial and viral infections.

Advantages:

• Stopping the growth of new pathogens while killing existing ones.
• Can treat strains that are currently resistant to the particular class of antibiotics