Double duplex invasion by peptide nucleic acid: A general principle for sequence-specific targeting of double-stranded DNA
Double duplex invasion by peptide nucleic acid: A general principle for sequence-specific targeting of double-stranded DNA
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DOI：
10.1073/pnas.96.21.11804
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发表时间：
1999-10-12
影响因子：
11.1
通讯作者：
Nielsen, PE
中科院分区：
文献类型：
--
作者：
Lohse, J;Dahl, O;Nielsen, PE
含有二氨基嘌呤硫尿嘧啶碱基对的伪互补 PNA 已被制备出来，并显示出通过一种称为“双链体入侵”的机制，以高特异性和效率与双链 DNA 中的互补靶标结合，其中双链体被解开，两条 DNA 链同时被两个伪互补肽核酸之一靶向 （PNAs）。根据我们的结果，我们预测（对于十聚体目标）超过 80% 的序列可以通过使用目前形式的这种方法通过简单的 Watson-Crick 碱基配对来定位。将假互补 PNA 靶向 T7 噬菌体 RNA 聚合酶的启动子可有效抑制转录起始。这些结果对于基因治疗剂的开发以及遗传诊断和分子生物学应用具有重要意义。
Pseudocomplementary PNAs containing diaminopurine thiouracil base pairs have been prepared and are shown to bind with high specificity and efficiency to complementary targets in double-stranded DNA by a mechanism termed "double duplex invasion" in which the duplex is unwound and both DNA strands are targeted simultaneously, each by one of the two pseudocomplementary peptide nucleic acids (PNAs). On the basis of our results we predict that (for decameric targets) more than 80% of all sequences can be targeted by straightforward Watson-Crick base pairing by using this approach in its present form. Targeting of pseudocomplementary PNAs to the promoter of the T7 phage RNA polymerase effectively inhibits transcription initiation. These results have important implications in the development of gene therapeutic agents as well as for genetic diagnostic and molecular biology applications.