设计基本的金属依赖DNA识别和细胞内化
Soraya Learte-Aymamí1, Natalia Curado1, Jéssica Rodríguez1
1Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS) and Departamento de Química Orgánica, Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain.
Journal of the American Chemical Society
|October 24, 2017
概括
研究人员设计了一种可选择性地将DNA与结合的. 这种金属促进的相互作用是可逆的,并使进入细胞.
科学领域:
- 生物化学
- 分子生物学
- 化学生物学
背景情况:
- GCN4 bZIP转录因子在基因调节中起作用.
- 为特定的DNA相互作用设计是分子生物学的一个关键领域.
研究的目的:
- 设计一种具有选择性DNA结合能力的.
- 研究金属依赖性和可逆性DNA相互作用.
- 探索金属诱导的细胞内化.
主要方法:
- 修改GCN4基本区域 (br) 以包括胺残留物 (brHis2).
- 使用共识目标DNA位点 (5'-GTCAT-3') 评估DNA结合亲和力和选择性.
- 使用 (Pd) 复合物 (Cl2) 促进-DNA相互作用.
- 研究可逆复合物分解与合剂.
- 评估带有或没有试剂的的细胞膜转位.
主要成果:
- 单独修改的 (brHis2) 没有与目标DNA序列结合.
- 添加Pd(en) Cl2导致brHis2与DNA的高度亲和和选择性结合.
- 与DNA的相互作用是可逆的,可以使用复合物和化剂多次切换.
- 帕拉治疗诱导了brHis2的有效细胞内化.
结论:
- 一个设计的可以实现选择性,主要沟DNA结合.
- 金属依赖相互作用提供了可逆控制DNA结合的机制.
- 可以促进细胞中基本的内化.
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