Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T-1Z1 (Canada).
Chemistry. 2014 Feb 3;20(6):1495-9. doi: 10.1002/chem.201303867. Epub 2014 Jan 17.
Janus bases are heterocyclic nucleic acid base analogs that present two different faces able to simultaneously hydrogen bond to nucleosides that form Watson-Crick base pairs. The synthesis of a Janus-AT nucleotide analogue, (N)JAT , that has an additional endocyclic ring nitrogen and is thus more capable of efficiently discriminating T/A over G/C bases when base-pairing in a standard duplex-DNA context is described. Conversion to a phosphoramidite ultimately afforded incorporation into an oligonucleotide. In contrast to the first generation of carbocyclic Janus heterocycles, it remains in its unprotonated state at physiological pH and, therefore, forms very stable Watson-Crick base pairs with either A or T bases. Biophysical and computational methods indicate that (N)JAT is an improved candidate for sequence-specific genome targeting.
双氮杂环戊烷碱基是杂环核酸碱基类似物，具有两个不同的面，能够同时与形成 Watson-Crick 碱基对的核苷形成氢键。本文描述了一种双氮杂环戊烷-AT 核苷酸类似物 (N)JAT 的合成，它具有额外的内环氮原子，因此在标准双链 DNA 环境中碱基配对时，能够更有效地区分 T/A 与 G/C 碱基。最终转化为磷酰胺，可掺入寡核苷酸中。与第一代碳环双氮杂环戊烷不同，它在生理 pH 值下仍保持非质子化状态，因此与 A 或 T 碱基形成非常稳定的 Watson-Crick 碱基对。生物物理和计算方法表明，(N)JAT 是一种用于序列特异性基因组靶向的改良候选物。
