BIOANALYSIS--DRUG/PROTEIN INTERACTIONS

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The research proposed here involves bioanalytical studies of drug/protein interactions. It is proposed that a new instrumental approach to fluorescence detected dichroism (FDCD) will be used as a probe for drug/protein interactions. The FDCD instrumentation provides rapid acquisition of FDCD data and enhanced capabilities for Interpretation of optically active multicomponent fluorescence mixtures. The use of this instrumentation for selectively monitoring chiral quenching provides a powerful tool for studying protein binding of fluorescence drugs. Specifically, the overall project is divided into three areas: 1) the use of FDCD measurements to aid in understanding the binding of fluorescent drugs to human serum albumin (HSA) and select fragments of HSA; 2) the development of novel algorithms to aid in the analysis and interpretation of the acquired data and 3) the combination of FDCD measurement with other parameters of fluorescence such as quenching, depolarization and lifetimes, as well as other instrumental techniques such as IR and NMR to provide a more useful probe of the drug binding sites in selected proteins.