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，要求提供资金以促进基础生物和化学过程背后的科学研究。拟议研究的目标包括确定新的抗生素作用的细菌蛋白质靶标，作为潜在抗生素的酶抑制剂的化学合成，以及表征负离子在气相中的基本反应活性。后者将回答我们在理解用于离子分析的过程中的重要问题，质谱分析是药物开发期间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，不仅被结合到蛋白质中，而且作为细菌细胞壁的组成部分，在哺乳动物中起到神经递质的作用。此外，氨基酸是与牙周病相关的厌氧菌的主要碳、氮和能量来源，牙周病会导致牙龈组织降解，并增加患冠心病的风险。厌氧细菌中氨基酸的代谢与人类不同；我们的研究将进一步定义这些差异，目标是开发有效和选择性的代谢抑制剂，这些都是潜在的抗生素。总体而言，我们在生物有机化学方面的研究计划将为细菌新陈代谢和生物相关分子的质谱学提供重要的见解，为解释和应用基本过程产生新的机制。

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.