Department of Chemistry and RINS, Gyeongsang National University, Jinju, Gyeongnam 660-701, Molecular-Level Interface Research Center, Department of Chemistry, KAIST, Daejeon 305-701, Republic of Korea.
Nucleic Acids Res. 2011 Sep 1;39(16):7329-35. doi: 10.1093/nar/gkr360. Epub 2011 May 17.
Peptide nucleic acids (PNA) are one of the most widely used synthetic DNA mimics where the four bases are attached to a N-(2-aminoethyl)glycine (aeg) backbone instead of the negative-charged phosphate backbone in DNA. We have developed a chimeric PNA (chiPNA), in which a chiral GNA-like γ(3)T monomer is incorporated into aegPNA backbone. The base pair opening kinetics of the aegPNA:DNA and chiPNA:DNA hybrid duplexes were studied by NMR hydrogen exchange experiments. This study revealed that the aegPNA:DNA hybrid is much more stable duplex and is less dynamic compared to DNA duplex, meaning that base pairs are opened and reclosed much more slowly. The site-specific incorporation of γ(3)T monomer in the aegPNA:DNA hybrid can destabilize a specific base pair and its neighbors, maintaining the thermal stabilities and dynamic properties of other base pairs. Our hydrogen exchange study firstly revealed the unique kinetic features of base pairs in the aegPNA:DNA and chiPNA:DNA hybrids, which will provide an insight into the development of methodology for specific DNA recognition using PNA fragments.
肽核酸 (PNA) 是应用最广泛的人工合成 DNA 模拟物之一，其中四个碱基连接到 N-(2-氨乙基)甘氨酸 (aeg) 骨架上，而不是 DNA 中的带负电荷的磷酸骨架。我们开发了一种嵌合 PNA (chiPNA)，其中一个手性 GNA 样 γ(3)T 单体被整合到 aegPNA 骨架中。通过 NMR 氢交换实验研究了 aegPNA:DNA 和 chiPNA:DNA 杂交双链的碱基对打开动力学。这项研究表明，与 DNA 双链相比，aegPNA:DNA 杂交双链更加稳定，动态性更低，这意味着碱基对的打开和重新闭合速度要慢得多。γ(3)T 单体在 aegPNA:DNA 杂交双链中的特异性掺入可以使特定的碱基对及其相邻碱基对不稳定，同时保持其他碱基对的热稳定性和动态性质。我们的氢交换研究首次揭示了 aegPNA:DNA 和 chiPNA:DNA 杂交双链中碱基对的独特动力学特征，这将为使用 PNA 片段进行特定 DNA 识别的方法学发展提供深入了解。
