MOLECULAR MIMICRY OF RECEPTORS FOR ALKALOID DRUGS

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The long term objective is to understand how various biological receptor systems interact with narcotic alkaloid drugs. This research project seeks to gain a preliminary insight into the physiochemical rules governing specific recognition and binding of morphine, nicotine and related drugs of abuse using modern molecular biology, biophysical measurements and supramolecular computational chemistry. The objective will be accomplished using theoretical and experimental molecular modelling studies in which we will use antibody-ligand binding sites as a paradigm of receptor-ligand -interactions. Antibodies which mimic biological receptor sites in terms of their stereospecific recognition and binding of ligands can serve as a model for the study of interactive constituents of both the ligand and receptor. Using quantitative structure-activity ligand binding studies, ligand induced fluorescence quenching, mRNA/cDNA sequencing techniques, computer-aided modelling and dynamics simulations and x-ray crystallography diffraction studies, we will extensively characterize the binding sites of monoclonal antibodies (mAb) which bind the alkaloid drugs morphine and nicotine. Antibody binding sites have been examined in numerous investigations, but this study is the first of its kind to use theoretical and experimental approaches to characterize the binding sites for narcotic drugs. It is imperative that we understand the basis of receptor-drug interactions so that strategies in treating drug abuse and new pharmaceuticals may be developed in a rational and predictive manner.