一个来自图书馆的 BZLF1 转录因子的抑制剂
Sarah K Madden1,2,3, Andrew Brennan1, Jody M Mason1
1Department of Life Sciences, University of Bath, Bath, UK.
概括
研究人员开发了一个新的选平台,以找到阻断转录因子 (TF) 功能的. 一个衍生的酸,AcidicW,通过稳定其二元并阻止DNA结合,强烈抑制BZLF1TF.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
背景情况:
- 转录因子 (TF) 失调与癌症等疾病有关.
- 基于的分子是细胞内蛋白质与蛋白质相互作用的有效调节剂.
- 目前的TF抑制剂选优先考虑结合亲和力而不是功能性抑制.
研究的目的:
- 调整转录块存活 (TBS) 选平台,用于高通量识别功能性TF抑制剂.
- 使用TBS平台推导一种针对BZLF1转录因子的强抑制剂.
主要方法:
- 利用转录块生存 (TBS) 选平台进行高通量选.
- 选的类库以识别阻止TF-DNA结合和功能的抑制剂.
- 描述了衍生 (AcidicW) 与BZLF1及其DNA结合部位的相互作用.
主要成果:
- 从选的库中确定了一个功能性抑制剂,AcidicW.
- 与BZLF1相比,AcidicW与本地BZLF1同位体 (Tm > 80°C) 形成了一个更稳定的二元体.
- 酸性W 强烈抑制 BZLF1:TRE DNA 相互作用,其 IC50 为 612 nM.
结论:
- TBS平台成功地识别了转录因子的功能性抑制剂.
- 酸是一种强大的BZLF1活性抑制剂,提供了潜在的治疗策略.
- 针对TF-DNA相互作用的基于的抑制剂代表了治疗疾病的有希望的方法.
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