Wittung P, Nielsen P, Nordén B
Department of Physical Chemistry, Chalmers University of Technology, S-41296 Gothenburg, Sweden.
Biochemistry. 1997 Jul 1;36(26):7973-9. doi: 10.1021/bi963136b.
Peptide nucleic acid (PNA) is an oligonucleotide mimic in which the backbone of DNA has been replaced by a pseudopeptide. Thymine-rich homopyrimidine PNA oligomers have been found to recognize double-stranded DNA targets by displacement of the pyrimidine DNA strand and forming an internal Watson-Crick-Hoogsteen base-paired PNA(pyr)-DNA(pu)-PNA(pyr) triplex. We here show that cytosine-rich homopyrimidine PNA sequences instead add to double-stranded polynucleotide targets as Hoogsteen strands forming PNA(pyr)-DNA(pu)-DNA(pyr) triplexes. Furthermore, PNA strands with homopurine or alternating thymine-guanine sequences are shown to invade their respective DNA targets by displacing the identical DNA strands of the polynucleotides and forming new PNA-DNA duplexes. These results indicate distinct mechanistic variations as to how PNA interacts with a DNA target depending on choice of nucleobases, which could be of importance for future design of gene-specific diagnostic or therapeutic agents.
肽核酸（PNA）是一种寡核苷酸类似物，其中DNA的主链已被假肽取代。富含胸腺嘧啶的同嘧啶PNA寡聚物已被发现通过取代嘧啶DNA链并形成内部沃森-克里克-霍赫施泰因碱基配对的PNA（pyr）-DNA（pu）-PNA（pyr）三链体来识别双链DNA靶标。我们在此表明，富含胞嘧啶的同嘧啶PNA序列反而作为霍赫施泰因链添加到双链多核苷酸靶标上，形成PNA（pyr）-DNA（pu）-DNA（pyr）三链体。此外，具有同嘌呤或交替胸腺嘧啶-鸟嘌呤序列的PNA链通过取代多核苷酸中相同的DNA链并形成新的PNA-DNA双链体来侵入其各自的DNA靶标。这些结果表明，根据核碱基的选择，PNA与DNA靶标相互作用的机制存在明显差异，这可能对未来基因特异性诊断或治疗剂的设计具有重要意义。
