Discipline of Natural Sciences, Indian Institute of Information Technology, Design, and Manufacturing, Khamaria, Jabalpur, India.
J Biomol Struct Dyn. 2023 Jan;41(1):366-376. doi: 10.1080/07391102.2021.2003863. Epub 2021 Nov 19.
To expand the existing genetic letters beyond the natural four nucleotides, such as G, C, A, and T, it is necessary to design robust nucleotides that can not only produce stable and unperturbed DNA but also function naturally in living cells. Although hydrophobic bases, such as d5SICS (2,6-dimethyl-2-isoquiniline-1-thione) and dNaM (2-methoxy-3-methylnaphthalene) were shown to be replicated in bacterial cells, the d5SICS:dNaM base-pair was found to perturb the structure of the duplex DNA. Therefore, it is necessary to design nucleobases that can form base pairs like the natural G:C and A:T pairs. Here, a reliable dispersion-corrected density functional theory has been used to design several nucleobases that can produce three-hydrogen-bonded base pairs like the G:C pair. In doing so, the Watson-Crick faces of d5SICS and dNaM were modified by replacing the hydrophobic groups with hydrogen bond donors and acceptors. As dNaM contains an unnatural -glycosidic bond (-dNaM), it was also modified to contain the natural -glycosidic bond (-dNaM). This technique produced 91 new bases (-d5SICS-X ( = 1-33), -dNaM-X ( = 1-35), and -dNaM-X ( = 1-23), where is the different types of modifications applied to d5SICS and dNaM) and 259 base-pairs. Among these base pairs, 76 base pairs are found to be more stable than the G:C pair. Interestingly, the -d5SICS-32:-dNaM-32 and -d5SICS-32:-dNaM-20 pairs are found to be the most stable with binding energies of about -28.0 kcal/mol. The base-pair patterns of these pairs are also analogous to that of the G:C pair. Hence, it is proposed that -d5SICS-32, -dNaM-32, and -dNaM-20 would act as efficient new genetic letters to produce stable and unperturbed artificial DNA.Communicated by Ramaswamy H. Sarma.
为了将现有的遗传字母扩展到天然的四个核苷酸（G、C、A 和 T）之外，有必要设计出能够不仅产生稳定且不受干扰的 DNA，而且还能在活细胞中自然发挥作用的稳健核苷酸。尽管疏水性碱基（如 d5SICS（2,6-二甲基-2-异喹啉-1-硫酮）和 dNaM（2-甲氧基-3-甲基萘））已被证明可在细菌细胞中复制，但 d5SICS:dNaM 碱基对被发现会干扰双链 DNA 的结构。因此，有必要设计出能够形成与天然 G:C 和 A:T 对类似的碱基对的核苷酸碱基。在这里，我们使用可靠的色散校正密度泛函理论来设计几种能够产生类似于 G:C 对的三氢键碱基对的核苷酸碱基。为此，通过用氢键供体和受体取代疏水性基团来修饰 d5SICS 和 dNaM 的 Watson-Crick 面。由于 dNaM 含有非天然的 -糖苷键（-dNaM），因此也对其进行了修饰以包含天然的 -糖苷键（-dNaM）。这种技术产生了 91 种新碱基（-d5SICS-X（=1-33）、-dNaM-X（=1-35）和 -dNaM-X（=1-23），其中 是应用于 d5SICS 和 dNaM 的不同类型修饰）和 259 种碱基对。在这些碱基对中，有 76 种碱基对比 G:C 对更稳定。有趣的是，-d5SICS-32：-dNaM-32 和 -d5SICS-32：-dNaM-20 对的结合能约为-28.0 kcal/mol，被发现是最稳定的。这些碱基对的碱基对模式也类似于 G:C 对。因此，我们提出 -d5SICS-32、-dNaM-32 和 -dNaM-20 将作为有效的新遗传字母，用于产生稳定且不受干扰的人工 DNA。由 Ramaswamy H. Sarma 传达。
