State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
J Med Chem. 2023 Aug 24;66(16):10934-10958. doi: 10.1021/acs.jmedchem.3c00881. Epub 2023 Aug 10.
Development of fluorescence polarization (FP) assays, especially in a competitive manner, is a potent and mature tool for measuring the binding affinities of small molecules. This approach is suitable for high-throughput screening (HTS) for initial ligands and is also applicable for further study of the structure-activity relationships (SARs) of candidate compounds for drug discovery. Buffer and tracer, especially rational design of the tracer, play a vital role in an FP assay system. In this perspective, we provided different kinds of approaches for tracer design based on successful cases in recent years. We classified these tracers by different types of ligands in tracers, including peptide, nucleic acid, natural product, and small molecule. To make this technology accessible for more targets, we briefly described the basic theory and workflow, followed by highlighting the design and application of typical FP tracers from a perspective of medicinal chemistry.
荧光偏振（FP）测定法的发展，特别是竞争型 FP 测定法，是一种强大而成熟的工具，可用于测量小分子的结合亲和力。这种方法适用于高通量筛选（HTS）初始配体，也适用于进一步研究候选化合物的结构-活性关系（SAR）以进行药物发现。缓冲液和示踪剂，尤其是示踪剂的合理设计，在 FP 测定系统中起着至关重要的作用。在这篇观点文章中，我们根据近年来的成功案例，提供了基于不同种类的示踪剂设计方法。我们根据示踪剂中配体的不同类型，将这些示踪剂进行了分类，包括肽、核酸、天然产物和小分子。为了使这项技术适用于更多的靶标，我们简要描述了基本理论和工作流程，然后从药物化学的角度重点介绍了典型 FP 示踪剂的设计和应用。
