Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka Suita, Osaka, 565-0871, Japan.
Chembiochem. 2020 Mar 16;21(6):860-864. doi: 10.1002/cbic.201900536. Epub 2019 Nov 29.
1,3-Diaza-2-oxophenoxazine ("phenoxazine"), a tricyclic cytosine analogue, can strongly bind to guanine moieties and improve π-π stacking effects with adjacent bases in a duplex. Phenoxazine has been widely used for improving duplex-forming abilities. In this study, we have investigated whether phenoxazine and its analogue, 1,3,9-triaza-2-oxophenoxazine (9-TAP), could improve triplex-forming abilities. A triplex-forming oligonucleotide (TFO) incorporating a phenoxazine component was found to show considerably decreased binding affinity with homopurine/homopyrimidine double-stranded DNA, so the phenoxazine system was considered not to function as either a protonated cytosine or thymine analogue. Alternatively, a 9-TAP-containing artificial nucleobase developed by us earlier as a new phenoxazine analogue functioned as a thymine analogue with respect to AT base pairs in a parallel triplex DNA motif. The fluorescence of the 9-TAP moiety was maintained even in triplex (9-TAP:AT) formation, so 9-TAP might be useful as an imaging tool for various oligonucleotide nanotechnologies requiring triplex formation.
1,3-二氮杂-2-氧杂吩嗪（“吩嗪”）是一种三环胞嘧啶类似物，能够与鸟嘌呤部分强烈结合，并改善双链体中相邻碱基的π-π堆积效应。吩嗪已被广泛用于提高双链体形成能力。在这项研究中，我们研究了吩嗪及其类似物 1,3,9-三氮杂-2-氧杂吩嗪（9-TAP）是否能够提高三聚体形成能力。发现含有吩嗪部分的三聚体形成寡核苷酸（TFO）与同嘌呤/同嘧啶双链 DNA 的结合亲和力显著降低，因此吩嗪系统不能作为质子化胞嘧啶或胸腺嘧啶类似物发挥作用。另一方面，我们之前开发的作为新型吩嗪类似物的含有 9-TAP 的人工碱基在平行三聚体 DNA 基序中与 AT 碱基对表现出类似胸腺嘧啶的作用。9-TAP 部分的荧光在三聚体（9-TAP:AT）形成中得以保持，因此 9-TAP 可能是用于需要三聚体形成的各种寡核苷酸纳米技术的成像工具。
