The characterization of specific metabolite–protein interactions is important in chemical biology and drug discovery. For example, nuclear receptors (NRs) are a family of ligand-activated transcription factors that regulate diverse physiological processes in animals and are key targets for therapeutic development. However, the identification and characterization of physiological ligands for many NRs remains challenging, because of limitations in domain-specific analysis of ligand binding in cells. To address these limitations, we developed a domain-specific covalent chemical reporter for peroxisome proliferator-activated receptors (PPARs) and demonstrated its utility to screen and characterize the potency of candidate NR ligands in live cells. These studies demonstrate targeted and domain-specific chemical reporters provide excellent tools to evaluate endogenous and exogenous (diet, microbiota, therapeutics) ligands of PPARs in mammalian cells, as well as additional protein targets for further investigation.

中文翻译：

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核受体化学报告基因可对哺乳动物细胞中的配体进行域特异性分析。

特定代谢物-蛋白质相互作用的表征在化学生物学和药物发现中很重要。例如，核受体 (NR) 是配体激活的转录因子家族，可调节动物的多种生理过程，是治疗开发的关键靶标。然而，许多 NR 的生理配体的鉴定和表征仍然具有挑战性，因为细胞中配体结合的域特异性分析存在局限性。为了解决这些限制，我们开发了一种针对过氧化物酶体增殖物激活受体 (PPAR) 的域特异性共价化学报告基因，并展示了其在活细胞中筛选和表征候选 NR 配体效力的效用。