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Fluorescent assay can find potential anti-HIV drugs

Apr 2007
Current antiretroviral drugs can slow the onset of AIDS, but no cure exists for the disease, so new drugs must be developed. Researchers at the University of California, San Diego, in La Jolla have developed a fluorescent assay that can screen for potential drugs that act on the dimerization initiation site, a portion of the HIV genome that has not been thoroughly explored for antiviral treatments.

As its name implies, the dimerization initiation site brings HIV’s two RNA strands together, or dimerizes them, critical for viral replication. During the process, the nucleotides that comprise the site form a “kissing loop” complex resembling pursed lips. RNA constructs that mimic the kissing loop serve as the basis of the fluorescent assay because any drug that binds the constructs may interfere with viral replication. For the fluorophore, the researchers used 2-amino-purine because it has the molecular recognition properties of a natural nucleotide, owing to its similar structure.

They tested the assay with the few drugs known to bind to the dimerization initiation site, as well as the analogs of those drugs. For those eight compounds, the assay showed quantitative, real-time and dose-dependent fluorescence intensity increases that ranged from 75 to 300 percent. The researchers demonstrated that the assay works and used it to quantify the binding affinities of the known binders for the first time, providing a measure of their effectiveness. They reported their findings in the March 21 issue of the Journal of the American Chemical Society.

Besides testing known binders, they examined the ability of previously untested but structurally related drugs to bind to the dimerization initiation site. They discovered that apramycin binds to the site, indicating that the drug could be a potential HIV treatment. In the future, they plan to develop new antiretroviral drugs as well as new fluorophores to improve the assay, said senior author Yitzhak Tor.

antiretroviral drugsAs We Go To PressBiophotonicsBreaking Newsfluorescent assayPresstime BulletinRNA strands

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