A Chemical Proteomic Workflow for Rapid Identification of Proteins Responsible for Metabolic Insecticide Resistance

代谢抗性通常是解毒酶(如细胞色素P450)表达增加或底物专一性改变导致杀虫剂解毒能力增强的结果(S)。由于昆虫编码&gt；100解毒酶，因此往往不能快速确定负责的酶(S)。我们假设化学蛋白质组学方法可以加速候选基因/蛋白质的鉴定。本项目旨在通过比较光亲和标记(PAL)、基于活性的蛋白质图谱(ABPP)和药物亲和反应靶标(DARTS)图谱来研究基于杀虫剂的探针分子，以识别与代谢抗性有关的酶。抗性机制的阐明将支持基于假设的下一代分子的设计，这些分子不受这种抗性机制的影响。

Metabolic resistance is commonly a result of either elevated expression of detoxifying enzymes (e.g. cytochrome P450s) or a shift in substrate specificity in those enzymes leading to an increased capacity to detoxify insecticide(s). The responsible enzyme(s) can often not be identified rapidly since insects encode >100 detoxification enzymes. We hypothesize that a chemical proteomic approach can accelerate candidate gene/protein identification. This project aims to investigate insecticide based probe molecules to identify enzymes involved in metabolic resistance by comparing photoaffinity labeling (PAL), activity based protein profiling (ABPP) and drug affinity responsive target stability (DARTS) profiling. The elucidation of resistance mechanisms will support hypothesis based-design of next generation molecules which are not affected by this resistance mechanism.