Bioorganic chemistry

新药的发现是一项重要的智力和商业努力。在这项申请中，资金被要求推进基础生物和化学过程背后的科学。拟开展的研究目标包括鉴定抗生素作用的新细菌蛋白靶点，化学合成酶抑制剂作为潜在抗生素，以及表征负离子在气相中的基本反应性。后者将回答我们对质谱分析离子过程的理解中的重要问题，质谱是药物开发过程中药物代谢研究中使用的主要工具。我们的研究重点是氨基酸，这是一组重要的生物分子，不仅是蛋白质的组成部分，也是细菌细胞壁的组成部分，也是哺乳动物的神经递质。此外，氨基酸是与牙周病相关的厌氧细菌的碳、氮和能量的主要来源，牙周病会导致牙龈组织降解并增加患冠心病的风险。厌氧菌的氨基酸代谢与人类不同；我们的研究将进一步确定这些差异，以开发有效和选择性的代谢抑制剂作为潜在的抗生素。总的来说，我们在生物有机化学方面的研究项目将为细菌代谢和生物相关分子的质谱分析提供重要的见解，为基本过程的解释和应用提供新的机制。

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.