OrthoSwitch Probes for High Throughput Screening

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DESCRIPTION (provided by applicant): This project aims to develop and test a rapid and sensitive screen for potential anti-nucleocapsid agents. The nucleocapsid (NC) and NC-containing precursor proteins from HIV-1 are targeted for drug discovery. NC is responsible for recognizing and packaging genomic RNA into new virus particles. In addition, the protein participates in other important viral processes, so anti-NC drugs could interfere at several stages of the life cycle of the virus. The screening procedure is a novel application of fluorescence technology, that promises very high sensitivity and selectivity for anti-NC agents. It is capable of being easily scaled for high-throughput screening. The method can also provide an accurate determination of the equilibrium dissociation constants for NC-competitor complexes. In addition, the procedures for developing the fluorescent probes can be simply extended to additional targets in the HIV-1 system, and other pathogens.