Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Department of Biochemistry, University of Oxford, 3 Parks Road, Oxford OX1 3QU, UK.
ACS Infect Dis. 2021 Aug 13;7(8):2238-2249. doi: 10.1021/acsinfecdis.0c00618. Epub 2020 Nov 17.
The () parasite is the cause of Chagas disease, a neglected disease endemic in South America. The life cycle of the parasite is complex and includes transitions between distinct life stages. This change in phenotype (without a change in genotype) could be controlled by epigenetic regulation, and might involve the bromodomain-containing factors 1-5 (BDF1-5). However, little is known about the function of the BDF1-5. Here we describe a fragment-based approach to identify ligands for bromodomain-containing factor 3 (BDF3). We expressed a soluble construct of BDF3 in , and used this to develop a range of biophysical assays for this protein. Fragment screening identified 12 compounds that bind to the BDF3 bromodomain. On the basis of this screen, we developed functional ligands containing a fluorescence or F reporter group, and a photo-crosslinking probe for BDF3. These tool compounds will be invaluable in future studies on the function of BDF3 and will provide insight into the biology of .
（）寄生虫是恰加斯病的病原体，这种被忽视的疾病在南美洲流行。寄生虫的生命周期很复杂，包括不同生命阶段之间的转变。这种表型的改变（基因型不变）可能受到表观遗传调控的控制，可能涉及包含溴结构域的因子 1-5（BDF1-5）。然而，关于 BDF1-5 的功能知之甚少。在这里，我们描述了一种基于片段的方法来鉴定 3 溴结构域包含因子（BDF3）的配体。我们在 中表达了 BDF3 的可溶性构建体，并利用它开发了一系列针对该蛋白的生物物理测定法。片段筛选鉴定出 12 种与 BDF3 溴结构域结合的化合物。基于该筛选，我们开发了包含荧光或 F 报告基团以及用于 BDF3 的光交联探针的功能性配体。这些工具化合物将对 BDF3 功能的未来研究非常有价值，并将深入了解 （）的生物学。
