PNA HYBRIDIZES TO COMPLEMENTARY OLIGONUCLEOTIDES OBEYING THE WATSON-CRICK HYDROGEN-BONDING RULES
PNA HYBRIDIZES TO COMPLEMENTARY OLIGONUCLEOTIDES OBEYING THE WATSON-CRICK HYDROGEN-BONDING RULES
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DOI：
10.1038/365566a0
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发表时间：
1993-10-07
期刊：
影响因子：
64.8
通讯作者：
NIELSEN, PE
中科院分区：
文献类型：
--
作者：
EGHOLM, M;BUCHARDT, O;NIELSEN, PE
由于DNA类似物作为基因靶向药物的潜力，目前正受到广泛的研究[1-3]。此外，它们的性质和与DNA和RNA的相互作用可以更好地理解自然DNA的结构特征，这些结构特征决定了其独特的化学、生物和遗传特性3,4。我们最近设计了一种DNA类似物PNA，其主链在结构上与脱氧核糖主链是同构的，并由核碱基连接的N-（2-氨基乙基）甘氨酸单元组成[5-9]。我们发现，仅含有胸腺嘧啶和胞嘧啶的PNA低聚物可以与互补的寡核苷酸杂交，可能是通过形成沃森-克里克- hoogsteen (PNA)2-DNA三联体，这比相应的DNA-DNA双联体更稳定5-7，并通过链位移与双链DNA结合5,8。我们在这里报告含有所有四种天然核碱基的PNA与遵循沃森-克里克碱基配对规则的互补寡核苷酸杂交，因此在碱基对识别方面是一个真正的DNA模拟物。
DNA ANALOGUES are currently being intensely investigated owing to their potential as gene-targeted drugs1-3. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties3,4. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to which the nucleobases are attached5-9. We showed that PNA oligomers containing solely thymine and cytosine can hybridize to complementary oligonucleotides, presumably by forming Watson-Crick-Hoogsteen (PNA)2-DNA triplexes, which are much more stable than the corresponding DNA-DNA duplexes5-7, and bind to double-stranded DNA by strand displacement5,8. We report here that PNA containing all four natural nucleobases hybridizes to complementary oligonucleotides obeying the Watson-Crick base-pairing rules, and thus is a true DNA mimic in terms of base-pair recognition.