使用化学蛋白质组学平台绘制反应性化学物质的全蛋白质组相互作用图谱。
Mapping proteome-wide interactions of reactive chemicals using chemoproteomic platforms.
作者信息
Counihan Jessica L, Ford Breanna, Nomura Daniel K
机构信息
Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, United States.
Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, United States.
出版信息
Curr Opin Chem Biol. 2016 Feb;30:68-76. doi: 10.1016/j.cbpa.2015.11.007. Epub 2015 Nov 30.
A large number of pharmaceuticals, endogenous metabolites, and environmental chemicals act through covalent mechanisms with protein targets. Yet, their specific interactions with the proteome still remain poorly defined for most of these reactive chemicals. Deciphering direct protein targets of reactive small-molecules is critical in understanding their biological action, off-target effects, potential toxicological liabilities, and development of safer and more selective agents. Chemoproteomic technologies have arisen as a powerful strategy that enable the assessment of proteome-wide interactions of these irreversible agents directly in complex biological systems. We review here several chemoproteomic strategies that have facilitated our understanding of specific protein interactions of irreversibly-acting pharmaceuticals, endogenous metabolites, and environmental electrophiles to reveal novel pharmacological, biological, and toxicological mechanisms.
大量药物、内源性代谢物和环境化学物质通过与蛋白质靶点的共价机制发挥作用。然而，对于大多数这些反应性化学物质而言，它们与蛋白质组的具体相互作用仍不清楚。解读反应性小分子的直接蛋白质靶点对于理解其生物学作用、脱靶效应、潜在毒理学风险以及开发更安全、更具选择性的药物至关重要。化学蛋白质组学技术已成为一种强大的策略，能够直接在复杂生物系统中评估这些不可逆试剂与蛋白质组的相互作用。我们在此综述了几种化学蛋白质组学策略，这些策略有助于我们理解不可逆作用药物、内源性代谢物和环境亲电试剂的特定蛋白质相互作用，以揭示新的药理、生物学和毒理学机制。
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