Design of artificial transcriptional activators with rigid poly-L-proline linkers
Design of artificial transcriptional activators with rigid poly-L-proline linkers
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DOI：
10.1021/ja0208355
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发表时间：
2002-11-06
影响因子：
15
通讯作者：
Dervan, PB
中科院分区：
文献类型：
--
作者：
Arora, PS;Ansari, AZ;Dervan, PB
典型的真核转录激活因子由不同的功能结构域组成，包括DNA结合结构域和激活结构域。已经设计了人工转录因子，其中DNA结合结构域是小沟DNA结合发夹聚酰胺，其通过柔性系链连接到短活化肽，通常大小为16-20个残基。在这项研究中，聚酰胺和肽之间的接头以递增的方式使用18-45埃长度范围内的刚性低聚脯氨酸“分子标尺”改变。我们发现，存在一个最佳的连接子长度，它将DNA和转录激活区分开。
Typical eukaryotic transcriptional activators are composed of distinct functional domains, including a DNA binding domain and an activating domain. Artificial transcription factors have been designed wherein the DNA binding domain is a minor groove DNA binding hairpin polyamide linked by a flexible tether to short activating peptides, typically 16-20 residues in size. In this study, the linker between the polyamide and the peptide was altered in an incremental fashion using rigid oligoproline "molecular rulers" in the 18-45 Angstrom length range. We find that there is an optimal linker length which separates the DNA and the activation region for transcription activation.