Post-modification of triazole-linked analogues of DNA for positively charged variants

无磷电子中性DNA类似物最常见的问题之一是低聚物的溶解度低。尽管缺乏带负电荷的磷酸键有利于化学和生物稳定性，但电中性链缺乏静电支持的溶解性。当我们制备TLDNA的长低聚物时，这个溶解性问题也出现了。具体来说，TLDNA同源物的独特功能，如诱导逆转录酶的底物，促使我们探索更长的低聚物的进一步应用，但随着低聚物的延长，溶解性问题变得更加严重。我们报道了一种简洁的后修饰方法，用于制备带正电的变异TLDNA+。低胸腺嘧啶TLDNA的一步甲基化成功地提高了TLDNA+的溶解度和产率。除了汞介导的自双相外，五聚体TLDNA+与天然低聚腺嘌呤DNA形成三螺旋结构。

One of the most common problems accompanied with non-phosphorus, electroneutral DNA analogues is the low solubility of the oligomers. Despite the chemical and biological stability benefitted from the absence of the negatively charged phosphate linkages, the electroneutral strand lacks electrostatic supports for the solubility. This solubility issue also arose, when we prepared long oligomers of TLDNA. Specifically, unique functions of TLDNA congeners such as lure substrates for reverse-transcriptase prompted us to explore further applications with longer oligomers, but the solubility problem became severer as the oligomers lengthened. We reported a concise post-modification method for the preparation of positively charged variants, TLDNA+. A one-step methylation of oligothymine TLDNA successfully afforded TLDNA+ with an improved solubility in high yield. The pentamer TLDNA+ formed a triple helix with natural oligoadenine DNA in addition to a mercury-mediated self-duplex.