Egholm M, Buchardt O, Christensen L, Behrens C, Freier S M, Driver D A, Berg R H, Kim S K, Norden B, Nielsen P E
Department of Organic Chemistry, H. C. Orsted Institute, Copenhagen, Denmark.
Nature. 1993 Oct 7;365(6446):566-8. doi: 10.1038/365566a0.
DNA analogues are currently being intensely investigated owing to their potential as gene-targeted drugs. 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 properties. 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 attached. 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 duplexes, and bind to double-stranded DNA by strand displacement. 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.
由于DNA类似物作为基因靶向药物的潜力，目前正在对其进行深入研究。此外，它们的性质以及与DNA和RNA的相互作用可以让人们更好地理解决定天然DNA独特化学、生物学和遗传特性的结构特征。我们最近设计了一种DNA类似物——肽核酸（PNA），其主链在结构上与脱氧核糖主链同形，由连接有核碱基的N-（2-氨基乙基）甘氨酸单元组成。我们发现，仅含有胸腺嘧啶和胞嘧啶的PNA寡聚物可以与互补寡核苷酸杂交，推测是通过形成沃森-克里克-霍赫施泰因（PNA）2-DNA三链体，这种三链体比相应的DNA-DNA双链体稳定得多，并且通过链置换与双链DNA结合。我们在此报告，含有所有四种天然核碱基的PNA按照沃森-克里克碱基配对规则与互补寡核苷酸杂交，因此就碱基对识别而言是一种真正的DNA模拟物。
