title: Assay Optimization and Screening of RNA-Protein Interactions by AlphaScreen.
abstract: The lack of lead compounds that specifically recognize and manipulate the function of RNA molecules limits our ability to consider RNA targets valid for drug discovery. Herein is reported a high-throughput biochemical screen for inhibitors of RNA-protein interactions based on AlphaScreen technology that incorporates several layers of specificity measurements into the primary screen. This screen was used to analyze approximately 5500 compounds from a collection of bioactive small molecules to detect inhibitors of the HIV-1 Rev-RRE and BIV Tat-TAR interactions. This proof-of-concept screen validates the assay as one that accurately identifies hit molecules and determines the selectivity of those hits.
authors.affiliation: Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, USA.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Mills
authors.forename: Anang A
authors.initials: AA
authors.lastname: Shelat
authors.forename: R Kiplin
authors.initials: RK
authors.lastname: Guy
mesh_terms: D001483:Base Sequence; D005454:Fluorescence Polarization / Q000379:methods*; D011485:Protein Binding; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA