Discovery metabolite profiling of the prolyl peptidases

阐明疾病背后的分子机制对于开发新药物至关重要 治疗剂。研究人员最近开发了许多方法来识别这些基因， 与疾病相关的蛋白质和代谢物。然而，定义连接的补充方法 这些分子之间的联系是疾病生物模型的基础， 医学已经证明更难发展。因此，仍然存在巨大的需求 创新的新方法，揭示了体内疾病分子成分之间的相互作用。的 下面的建议概述了继续发展和应用这样一种方法，称为发现 代谢物谱分析（METALITE PROPPING），用于将内源性底物分配给脯氨酰肽酶家族， 内切酶生物学整合了一系列生物学和化学方法，包括遗传学，药理学， 分析化学，以确定真正的生理酶底物相互作用。重要的是，通过使用 为了研究一个几乎缺乏已知内源性底物的酶家族， 表型的巨大生物医学利益，这项研究将开始实现令人难以置信的潜力， 脯氨酰肽酶在医学上的应用此外，将α-淀粉酶应用于肽酶将证明 这种方法的一般性，为未来的表征医学相关的酶和信号 途径。

Elucidation of the molecular mechanisms that underlie disease is crucial for the development of new therapeutic agents. Researchers have recently developed a number of methods to identify the genes, proteins, and metabolites associated with disease. However, complementary methods that define connections between these molecules—connections that are the foundation of biological models of disease and targeted medicine—have proven much more difficult to develop. As a result, there remains a tremendous need for innovative new approaches that reveal interactions between the molecular components of disease in vivo. The following proposal outlines the continued development and application of one such method, termed discovery metabolite profiling (DMP), for the assignment of endogenous substrates to the prolyl peptidase family of enzymes. DMP integrates an array of biological and chemical methods, including genetics, pharmacology, and analytical chemistry to identify bona fide physiological enzyme-substrate interactions. Importantly, by using DMP to study a family of enzymes that are virtually lacking in known endogenous substrates, but regulate phenotypes of tremendous biomedical interest, this research will begin to realize the incredible potential of the prolyl peptidases in medicine. Furthermore, the application of DMP to peptidases will demonstrate the generality of this approach for the future characterization of medically relevant enzymes and signaling pathways.