Advanced bioanalytical mass spectrometry methods for investigating the mechanism of protein binding by reactive metabolites

用于研究反应性代谢物的蛋白质结合机制的先进生物分析质谱方法

• 批准号: 355933-2011
• 负责人: Sleno, Lekha
• 金额: $ 2.55万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=507197
• 关键词: Advanced; bioanalytical; mass; spectrometry; methods

The main role of drug metabolism is to detoxify the body from xenobiotics, rendering them more polar and thus more easily cleared. Some drugs, however, are bioactivated into reactive metabolites with the potential to covalently bind to proteins. These reactive metabolites can bind to proteins in vivo and cause administration of these drugs to be potentially very dangerous. The goal of our research program is to design new innovative methods to study these toxic interactions. Our focus is to devise a strategy to further understand binding of reactive metabolites to proteins using a combination of modern mass spectrometry tools for studying both small molecules and proteins.

药物代谢的主要作用是使身体从外源性物质中解毒，使它们更具极性，从而更容易清除。然而，一些药物被生物活化成具有与蛋白质共价结合的潜力的活性代谢物。这些反应性代谢物可与体内蛋白质结合，并导致这些药物的给药具有潜在的非常危险性。我们研究计划的目标是设计新的创新方法来研究这些毒性相互作用。我们的重点是设计一种策略，以进一步了解结合的反应性代谢产物的蛋白质使用现代质谱工具研究小分子和蛋白质。