Development of a new strand-invader with artificial nucleotides

在本项目中，我们旨在通过结合未修饰的肽核酸（PNA）和修饰的DNA (TN -DNA)，开发一种新的链入侵者，其中涉及新的碱基替代物=苏氨酸-核苷酸（TN），该核苷酸将功能分子如插入物拴在d-苏氨酸上。作为一种可能的链入侵者，双工稳定性应按以下顺序排列；Dna / pna tn-dna / Dna > Dna / Dna > tn-dna / pna。首先，我们寻找了一种功能分子和将TN引入DNA的最佳方式，满足上述条件。我们发现带吸电子基团的平面分子（插层剂）能显著稳定DNA双链。此外，在DNA中每两个核苷酸处引入TN显著促进了与DNA的双链形成，并延缓了与PNA的杂交。在此基础上，我们将未修饰的PNA与含有蒽醌的TN-DNA结合作为链入侵者，成功侵入目标DNA双链。

In this project, we aimed at developing a new strand-invader by combining unmodified peptide nucleic acid (PNA) and modified DNA (TN -DNA) involving new base-surrogate=Threoninol-Nucleotide (TN) that tethers a functional molecule such as intercalator on D-threoninol. As a possible strand-invader, the duplex stability should be in the following order; DNA/PNA, TN-DNA/DNA > DNA/DNA > TN-DNA/PNA. First, we searched a functional molecule and optimum way of introducing TN into DNA that satisfies above requisites. We found that planar molecule (intercalator) with electron-withdrawing group could significantly stabilize the DNA duplex. Furthermore, introduction of TN at every two nucleotides into DNA remarkably facilitated the duplex formation with DNA and retarded hybridization with PNA. On the basis of these results, we combined unmodified PNA and TN-DNA involving anthraquinone as a strand-invader, which was successfully invaded into the target DNA duplex.