SSB-Assisted Duplex Invasion of Preorganized PNA into Double-Stranded DNA
SSB-Assisted Duplex Invasion of Preorganized PNA into Double-Stranded DNA
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DOI：
10.1002/cbic.200900381
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发表时间：
2009-11-02
期刊：
影响因子：
3.2
通讯作者：
Marchelli, Rosangela
中科院分区：
文献类型：
--
作者：
Ishizuka, Takumi;Tedeschi, Tullia;Marchelli, Rosangela
肽核酸（PNAs）是具有修饰骨架的DNA类似物，其中糖-磷酸部分被N-（2-氨基乙基）甘氨酸取代。[1]PNA是DNA链的非常好的结构模拟物，并且能够通过沃森-克里克规则形成非常稳定的双链体结构。这些双链体通常比相应DNA形成的双链体更稳定，而且PNA不会被酶降解。因此，PNA在化学、生物学和医学的许多领域都很受关注，包括药物发现、遗传诊断和分子识别。[2]为了改善PNA的良好结合特性，已经开发了具有骨架修饰的各种PNA衍生物。[3]研究最多的修饰之一是在PNA骨架内引入氨基酸衍生的立体中心，[4]例如D-赖氨酸a-PNA（DKa-PNA [5]）、L-丙氨酸g-PNA（LAg-PNA）[6]、L-丝氨酸g-PNA（LSg-PNA）[7]和L-赖氨酸g-PNA（LKg-PNA）。[8]此外，基于胍的PNA（GPNA，DRa-PNA）已被应用于体内实验以增加细胞摄取。[9]因此，修饰的PNA被广泛用作强有力的DNA识别工具。相比之下，dsDNA的识别更难实现，因为它需要置换DNA螺旋的一条链。识别双链DNA最成功的方法是通过使用假互补PNA（pcPNA），其中使用修饰的核碱基2，6-二氨基嘌呤（D）和2-硫氧嘧啶（Us）代替腺嘌呤（A）和胸腺嘧啶（T）;[10]这种技术用于各种生物学应用。[11]我们的小组已经报道了PNA的其他修饰。[12个]
Peptide nucleic acids (PNAs) are DNA analogues with modified backbones in which the sugar-phosphate moiety is replaced by N-(2-aminoethyl) glycine.[1] PNAs are extremely good structural mimics of the DNA strand and are able to form very stable duplex structures through the Watson–Crick rule. These duplexes are in general more stable than those formed by the corresponding DNA and, furthermore, PNAs are not enzymatically degraded. Therefore, PNAs are of interest in many areas of chemistry, biology, and medicine including drug discovery, genetic diagnostics, and molecular recognition.[2] In order to improve the favorable binding properties of PNAs, various PNA derivatives with backbone modifications have been developed.[3] One of the most studied modifications is the introduction of amino-acid-derived stereogenic centers within the PNA backbone,[4] such as D-lysine a-PNA (DKa-PNA [5]), L-alanine g-PNA (LAg-PNA),[6] L-serine g-PNA (LSg-PNA)[7] and L-lysine g-PNA (LKg-PNA).[8] Moreover, the guanidine-based PNA (GPNA, DRa-PNA) has been applied to in vivo experiments in order to increase cellular uptake.[9] Therefore, modified PNAs are widely used as a powerful DNA recognition tool. In contrast, recognition of dsDNA is more difficult to achieve, because it is necessary to displace one strand of the DNA helix. The most successful way to recognize dsDNA is through the use of pseudo-complementary PNA (pcPNA) in which the modified nucleobases 2, 6-diaminopurine (D) and 2-thiouracil (Us) are used in place of adenine (A) and thymine (T);[10] this technique is used for various biological applications.[11] Other modifications of PNA have been reported by our group.[12]