Liu Haibo, Gao Jianmin, Maynard Lystranne, Saito Y David, Kool Eric T
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA.
J Am Chem Soc. 2004 Feb 4;126(4):1102-9. doi: 10.1021/ja038384r.
We describe the design, preparation, and properties of two key building blocks of a size-expanded genetic system. Nucleoside analogues of the natural nucleosides dA and dT are reported in which the fusion of a benzo ring increases their size by ca. 2.4 A. The expanded dA analogue (dxA), having a tricyclic base, was first reported by Leonard nearly three decades ago. We describe a shortened and more efficient approach to this compound. The expanded dT analogue (dxT), a methylquinazolinedione C-glycoside, was previously unknown; we describe its preparation in eight steps from 5-methylanthranilic acid. The key glycoside bond formation employed Pd-mediated coupling of an aryl iodide precursor with a dihydrofuran derivative of deoxyribose. Both nucleosides are shown to be efficient fluorophores, emitting light in the blue-violet range. The base-protected phosphoramidite derivatives were prepared, and short oligonucleotides containing them were characterized. The two size-expanded nucleosides are key components of a new four-base genetic system designed to form helical paired structures having a diameter greater than that of natural DNA. Elements of the design of this expanded genetic molecule, termed xDNA, are discussed, including the possibility of up to eight base pairs of information storage capability.
我们描述了一种尺寸扩展的遗传系统的两个关键构建模块的设计、制备及性质。报道了天然核苷dA和dT的核苷类似物，其中苯环的融合使其尺寸增加了约2.4 Å。具有三环碱基的扩展dA类似物（dxA）早在近三十年前就由伦纳德首次报道。我们描述了一种更简短、更高效的合成该化合物的方法。扩展dT类似物（dxT），一种甲基喹唑啉二酮C-糖苷，此前并不为人所知；我们描述了从5-甲基邻氨基苯甲酸经八步反应制备它的方法。关键的糖苷键形成采用钯介导的芳基碘前体与脱氧核糖的二氢呋喃衍生物的偶联反应。两种核苷均显示为高效荧光团，在蓝紫色范围内发光。制备了碱基保护的亚磷酰胺衍生物，并对含有它们的短寡核苷酸进行了表征。这两种尺寸扩展的核苷是一种新的四碱基遗传系统的关键组成部分，该系统旨在形成直径大于天然DNA的螺旋配对结构。讨论了这种被称为xDNA的扩展遗传分子的设计要素，包括其具有存储多达八个碱基对信息的可能性。
