Center for Integrative Chemical Biology & Drug Discovery, Division of Chemical Biology & Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Future Med Chem. 2021 Apr;13(8):749-763. doi: 10.4155/fmc-2019-0274. Epub 2020 Jan 10.
The dynamic nature of histone post-translational modifications such as methylation or acetylation makes possible the alteration of disease associated epigenetic states through the manipulation of the associated epigenetic machinery. One approach is through small molecule perturbation. Chemical probes of epigenetic reader domains have been critical in improving our understanding of the biological consequences of modulating their targets, while also enabling the development of novel probe-based reagents. By appending a functional handle to a reader domain probe, a chemical toolbox of reagents can be created to facilitate chemiprecipitation of epigenetic complexes, evaluate probe selectivity, develop screening assays, visualize cellular target localization, enable target degradation and recruit epigenetic machinery to a site within the genome in a highly controlled fashion.
组蛋白翻译后修饰（如甲基化或乙酰化）的动态性质使得通过操纵相关的表观遗传机制来改变与疾病相关的表观遗传状态成为可能。一种方法是通过小分子干扰。表观遗传读码器结构域的化学探针在提高我们对调节其靶标的生物学后果的理解方面至关重要，同时也为新型基于探针的试剂的开发提供了可能。通过在读取器结构域探针上附加功能手柄，可以创建一个化学工具包试剂，以促进表观遗传复合物的化学沉淀、评估探针选择性、开发筛选测定、可视化细胞靶标定位、使靶标降解，并以高度可控的方式将表观遗传机制募集到基因组内的特定位置。
