FRET-based biosensor can screen for potential analgesic drugs

A team of researchers from the Neuropharmacology and Pain Research Group of the Bellvitge Biomedical Research Institute (IDIBELL), the University of Barcelona (UB), and ESTEVE (all in Barcelona, Spain) has developed a fluorescence resonance energy transfer (FRET)-based biosensor that can determine drugs' analgesic potential before being tested in animal models. The finding could save time and money in research on new, effective pain treatments.

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In a study led by Francisco Ciruela, senior lecturer of the Department of Pathology and Experimental Therapy at UB and a researcher in the Neuropharmacology and Pain Research Group, the researchers' FRET-based biosensor allowed them to classify—in cells in culture—ligands in sigma-1 receptor into agonists and antagonists.

The experiments established a direct correlation between the biosensor's FRET signal in response to the drugs and their analgesic effect in a pain animal model. Sigma-1 agonists reduce FRET signal and have low analgesic effects, whereas sigma-1 antagonists increase FRET signal and have high analgesic effects in pain animal models.

"Thanks to this well-defined pattern, we can predict the analgesic behavior of a molecule," explains Ciruela. "Therefore, if FRET signal is reduced—that is, if it is an agonist—it won’t have analgesic effects on the pain animal model. However, if FRET signal is increased—in other words, if it is an antagonist—it will have maximum analgesic effects and, therefore, it will be a suitable candidate to be tested in vivo."

Ciruela points out that the new technology has already been patented, with the expectation that it will be soon lead to a high-throughput screening method.

Full details of the work appear in the Journal of Medicinal Chemistry; for more information, please visit http://pubs.acs.org/doi/abs/10.1021/jm401529t.
   
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