Huang Yu Chuan, Castor Katherine J, Sleiman Hanadi F, Sen Dipankar
Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Department of Chemistry, McGill University, Montréal, Québec H3A 2K6, Canada.
Bioorg Med Chem. 2014 Aug 15;22(16):4376-83. doi: 10.1016/j.bmc.2014.05.023. Epub 2014 May 22.
Contractile duplexes are DNA double helices that incorporate two strategically placed patches of guanine-guanine (G·G) base mismatches. Such duplexes are cation-driven mechatronic devices, able to toggle between states with distinct mechanical and charge conduction properties. In aqueous lithium chloride solution contractile duplexes have an extended (E) and poorly conductive conformation; however, potassium ions drive them to a relatively conductive and structurally contracted (C) conformation, via intramolecular G-quadruplex formation. Here, we report that even in the absence of K(+) ions, a known G-quadruplex binding ligand, Pt-PIP [phenylphenanthroimidazole ethylenediamine platinum(II)] efficiently promotes the E→C transition, while a poor binder, Pt-bpy [bipyridine ethylenediamine platinum(II)], does not promote this transition. An examination of E→C transitions within two different designs for DNA contractile helices found an unexpected complexity: the formation of distinct C states, both electrically conductive, but possessing dissimilar DNA topologies. Ligand-driven DNA mechatronic devices such as these may constitute prototypes for electronic biosensors that identify G-quadruplex binding ligands.
收缩双链体是一种DNA双螺旋结构，其中包含两个经策略性定位的鸟嘌呤 - 鸟嘌呤（G·G）碱基错配区域。这种双链体是阳离子驱动的机电装置，能够在具有不同机械和电荷传导特性的状态之间切换。在氯化锂水溶液中，收缩双链体具有伸展（E）且导电性差的构象；然而，钾离子通过分子内G-四链体的形成，将它们驱动到相对导电且结构收缩（C）的构象。在此，我们报告，即使在没有钾离子的情况下，一种已知的G-四链体结合配体Pt-PIP [苯基菲咯咪唑乙二胺铂（II）]也能有效地促进E→C转变，而一种结合能力较差的配体Pt-bpy [联吡啶乙二胺铂（II）]则不能促进这种转变。对两种不同设计的DNA收缩螺旋内的E→C转变进行研究发现了一个意想不到的复杂性：形成了不同的C状态，两者都具有导电性，但拥有不同的DNA拓扑结构。像这样的配体驱动的DNA机电装置可能构成识别G-四链体结合配体的电子生物传感器的原型。
