Foundation for Molecular Evolution, 13709 Progress Boulevard, No. 7, Alachua, Florida 32615, United States.
Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, Indiana 46202, United States.
J Am Chem Soc. 2022 Aug 31;144(34):15603-15611. doi: 10.1021/jacs.2c05255. Epub 2022 Aug 15.
A fundamental property of DNA built from four informational nucleotide units (GCAT) is its ability to adopt different helical forms within the context of the Watson-Crick pair. Well-characterized examples include A-, B-, and Z-DNA. For this study, we created an isoinformational biomimetic polymer, built (like standard DNA) from four informational "letters", but with the building blocks being artificial. This ALternative Isoinformational ENgineered (ALIEN) DNA was hypothesized to support two nucleobase pairs, the : pair matching 2-amino-imidazo-[1,2]-1,3,5-triazin-[8]-4-one with 6-amino-3-5-nitro-1-pyridin-2-one and the : pair matching 6-amino-4-hydroxy-5-1-purin-2-one with 3-methyl-6-amino-pyrimidin-2-one. We report two structures of ALIEN DNA duplexes at 1.2 Å resolution and a third at 1.65 Å. All of these are built from a single self-complementary sequence (5'-CTAG) that includes 12 consecutive ALIEN nucleotides. We characterized the helical, nucleobase pair, and dinucleotide step parameters of ALIEN DNA in these structures. In addition to showing that ALIEN pairs retain basic Watson-Crick pairing geometry, two of the ALIEN DNA structures are characterized as A-form DNA and one as B-form DNA. We identified parameters that map differences effecting the transition between the two helical forms; these same parameters distinguish helical forms of isoinformational natural DNA. Collectively, our analyses suggest that ALIEN DNA retains essential structural features of natural DNA, not only its information density and Watson-Crick pairing but also its ability to adopt two canonical forms.
一种由四个信息核苷酸单位（GCAT）组成的 DNA 的基本性质是，它能够在沃森-克里克碱基对的背景下采用不同的螺旋形式。其中包括 A 型、B 型和 Z 型 DNA 等特征明确的例子。在这项研究中，我们创建了一种等信息的仿生聚合物，它由四个信息“字母”组成（与标准 DNA 相同），但构建块是人工的。这种替代等信息工程（ALIEN）DNA 被假设支持两种碱基对，即：碱基对匹配 2-氨基咪唑-[1,2]-1,3,5-三嗪-[8]-4-酮与 6-氨基-3-5-硝基-1-吡啶-2-酮，以及：碱基对匹配 6-氨基-4-羟基-5-1-嘌呤-2-酮与 3-甲基-6-氨基嘧啶-2-酮。我们报道了在 1.2 Å分辨率下的两种 ALIEN DNA 双链结构和第三种在 1.65 Å分辨率下的结构。所有这些结构都是由一个包含 12 个连续的 ALIEN 核苷酸的单一自互补序列（5'-CTAG）构建而成。我们在这些结构中表征了 ALIEN DNA 的螺旋、碱基对和二核苷酸步长参数。除了表明 ALIEN 碱基对保留了基本的沃森-克里克配对几何形状外，其中两种 ALIEN DNA 结构被特征化为 A 型 DNA，一种被特征化为 B 型 DNA。我们确定了映射影响两种螺旋形式之间转变的参数；这些相同的参数也可以区分等信息天然 DNA 的螺旋形式。总的来说，我们的分析表明，ALIEN DNA 保留了天然 DNA 的基本结构特征，不仅保留了其信息密度和沃森-克里克配对，还保留了其采用两种规范形式的能力。
