The Structure of a TNA-TNA Complex in Solution: NMR Study of the Octamer Duplex Derived from α-(L)-Threofuranosyl-(3′-2′)-CGAATTCG

The Structure of a TNA-TNA Complex in Solution: NMR Study of the Octamer Duplex Derived from α-(L)-Threofuranosyl-(3′-2′)-CGAATTCG
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DOI:
10.1021/ja8041959
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发表时间:
2008-11-12
影响因子:
15
通讯作者:
Jaun, Bernhard
Jaun, Bernhard
中科院分区:
化学1区
文献类型:
--
作者:
Ebert, Marc-Olivier;Mang, Christian;Jaun, Bernhard

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TNA(α-(L)-苏呋喃糖基-(3 '-2')核酸)是其中天然核酸RNA的呋喃核糖结构单元被呋喃四糖α-(L)-苏糖取代的核酸。与天然系统相比,这将主链的重复单元缩短了一个键。在我们的实验室迄今为止在病因学背景下研究的替代核酸结构中,TNA是唯一一种不仅与自身而且与DNA,甚至更强烈地与RNA表现出沃森-克里克配对的核酸结构。使用NMR光谱,我们已经确定了完全由TNA核苷酸组成的双链体的结构。TNA八聚体(3 '-2')-CGAATTCG形成具有根据沃森-克里克模式配对的反平行链的右手双螺旋。糖单元的主要构象在准双轴位置具有2 '-和3'-磷酸二酯取代基,并且对应于4 '-外折叠。在5.85埃的情况下,TNA的平均顺序P-i-Pi+1距离比A型DNA(6.2埃)短。螺旋参数,特别是滑动和x位移,以及浅而宽的小沟,将TNA双链体置于A型DNA和RNA的结构附近。
TNA (alpha-(L)-threofuranosyl-(3'-2') nucleic acid) is a nucleic acid in which the ribofuranose building block of the natural nucleic acid RNA is replaced by the tetrofuranose alpha-(L)-threose. This shortens the repetitive unit of the backbone by one bond as compared to the natural systems. Among the alternative nucleic acid structures studied so far in our laboratories in the etiological context, TNA is the only one that exhibits Watson-Crick pairing not only with itself but also with DNA and, even more strongly, with RNA. Using NMR spectroscopy, we have determined the structure of a duplex consisting entirely of TNA nucleotides. The TNA octamer (3'-2')-CGAATTCG forms a right-handed double helix with antiparallel strands paired according to the Watson-Crick mode. The dominant conformation of the sugar units has the 2'- and 3'-phosphodiester substituents in quasi-diaxial position and corresponds to a 4'-exo puckering. With 5.85 angstrom, the average sequential P-i-Pi+1 distances of TNA are shorter than for A-type DNA (6.2 angstrom). The helix parameters, in particular the slide and x-displacement, as well as the shallow and wide minor groove, place the TNA duplex in the structural vicinity of A-type DNA and RNA.