HIV FRAMESHIFT SITE RNA LIGAND INTERACTIONS

University Of Wisconsin-Madison, Madison WI

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.