HIV FRAMESHIFT SITE RNA LIGAND INTERACTIONS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The HIV-1 frameshift site RNA is an RNA structure that stimulates a programmed -1 ribosomal frameshift during translation. This frameshift is required for expression of the enzymatic proteins reverse transcriptase, integrase and protease. Thus this RNA structure is essential for viral replication. We have performed a high-throughput screen to search for small, drug-like molecules that bind to this RNA structure. From this screen, we have identified 202 positive hits as potential RNA-binding ligands. NMR time is requested to investigate the interaction of these small molelcules with the HIV-1 frameshift site RNA, and in turn how the RNA structure is affected by ligand binding. Experiments to be performed include 1D WATERLOGSY, 2D NOESY, 2D 1H-15N HSQC and 2D 1H-13C HSQC.