代体因子5作为抗莱什曼药物发现的目标
Catherine N Russell1, Jennifer L Carter2, Juliet M Borgia1
1York Structural Biology Laboratory and York Biomedical Research Institute, Department of Chemistry, University of York, York YO10 5DD, U.K.
ACS infectious diseases
|October 31, 2023
概括
研究人员探索了Leishmania donovani bromodomain factor 5 (LdBDF5) 作为一种新的药物标. LdBDF5基因与抑制剂结合,其中一种化合物对Leishmania寄生虫表现出活性.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 寄生虫学的寄生虫学
- 药物发现 药物发现 药物发现
背景情况:
- 莱什曼病是被忽视的热带疾病,治疗选择有限.
- 类人是表观遗传读者,在癌症和其他疾病中具有治疗潜力.
- 向寄生虫基组为抗莱什曼药物开发提供了一种新的策略.
研究的目的:
- 调查Leishmania donovani bromodomain factor 5 (LdBDF5) 作为治疗莱什曼病的潜在药物标.
- 为了描述 LdBDF5 原体的结合相互作用.
- 评估已知代胺抑制剂的抗莱什曼尼活性.
主要方法:
- 净化复合的LdBDF5原蛋白.
- 进行X射线晶体学以确定LdBDF5 BD5.2.2.的结构.
- 基斯顿微阵列和光极化测试以确定结合标.
- 生物物理测定 (热转移,NMR) 来确认抑制剂结合.
- 使用Leishmania promastigotes进行细胞活力测试.
主要成果:
- LdBDF5 含有两个原体 (BD5.1 和 BD5.2).
- LdBDF5 代蛋白与乙化组合素 (H2B,H4) 结合.
- BDF5 体蛋白与人类体蛋白抑制剂 (SGC-CBP30,体蛋白,I-BRD9) 相互作用.
- SGC-CBP30对莱什曼尼亚促进性菌体表现出活性.
结论:
- LdBDF5是抗莱什曼治疗的有希望的药物标.
- 鉴定的相互作用为开发针对LdBDF5.5的新药提供了基础.
- 进一步开发针对LdBDF5的化合物可能会导致利什曼病的有效治疗方法.
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