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Hitting moving RNA drug targets
Date:6/26/2011

these results because one of the biggest challenges in RNA-targeted drug discovery is to be able to identify compounds that bind a specific RNA target without binding other RNAs. The ability of netilmicin to specifically bind TAR provides proof of concept for this new technology," said Stelzer.

Further experiments showed that, for the six potential drug molecules, the method not only successfully predicted that they would bind to TAR, it also showed---with atomic-level accuracywhere on the RNA molecule each drug would bind.

Al-Hashimi then turned the six drug candidates over to David Markovitz, a professor of infectious diseases at the U-M Medical School, who tested them in cultured human T cells infected with HIV. The point of this experiment was to see if the drugs would prevent HIV from making copies of itself, an essential step in the disease process.

"Netilmicin did in fact inhibit HIV replication," Markovitz said. "This result demonstrates that using an NMR spectrometer and some computers we can discover drugs that target RNA and are active in human cells."

In addition to testing compounds in existing molecular libraries, the virtual screening technique can be used to explore the potential of new compounds that have not yet been synthesized, Al-Hashimi said. "This opens up a whole new frontier for exploring RNA as a drug target and finding new compounds that specifically target it."


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Contact: Nancy Ross-Flanigan
rossflan@umich.edu
734-647-1853
University of Michigan
Source:Eurekalert

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