Bioorganic chemistry

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The discovery of new pharmaceuticals is an important intellectual and commercial endeavour. In this application, funding is requested to advance the science behind fundamental biological and chemical processes. Objectives of the proposed research include the identification of new bacterial protein targets for antibiotic action, the chemical synthesis of enzyme inhibitors as potential antibiotics, and the characterization of the fundamental reactivity of negative ions in the gas phase. The latter will answer important questions in our understanding of processes used for the analysis of ions by mass spectrometry, the major tool used in drug metabolism studies during drug development. Our studies focus on amino acids, an important group of biomolecules that not only are incorporated into proteins, but also serve as integral components of the bacterial cell wall and act as neurotransmitters in mammals. In addition, amino acids are major sources of carbon, nitrogen and energy for anaerobic bacteria associated with periodontal disease, a disease that leads to degradation of gum tissue and increases the risk of coronary heart disease. The metabolism of amino acids in anaerobic bacteria differs from that in humans; our studies will further define these differences with the goal of developing effective and selective metabolic inhibitors that are potential antibiotics. Overall our research program in Bioorganic Chemistry will provide important insights into bacterial metabolism and mass spectrometry of biologically relevant molecules, yielding new mechanisms for the interpretation and application of fundamental processes.