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首页> 外文期刊>Biochemistry >Platination of the (T_2G_4)_4 Telomeric Sequence:A Structural and Cross-Linking Study
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Platination of the (T_2G_4)_4 Telomeric Sequence:A Structural and Cross-Linking Study

机译:(T_2G_4)_4端粒序列的电镀:结构和交联研究

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The telomeric sequence (T 2G4)4 was platinated in aqueous solutions containing 50 mM LiC1O4, NaC1O4, or KC1O4. The identification of the guanines which reacted with [Pt(NH3)3(H20)r+ revealed that the same type of folding exists in the presence of the three cations and that the latter determine the relative stabilities of the G-quadruplex structures in the order K+ > Na+ ? Li+. The tri-ammine complex yielded ca. 40-90% of adducts, mono- and poly-platinated, bound to 4 guanines out of the 16 guanines in the sequence, in the decreasing amounts G9 > G 15 ? G3 > G21. The formation of these adducts was interpreted with a G-quadruplex structure obtained by restrained molecular dynamics (rMD) simulations which confirms the schematic model proposed by Williamson et al. [(1989) Cell 59, 871-880]. The bifunctional complexes cis- and trans-[Pt(NH3)2(H20)2r+ also first reacted with G9 and G15 and gave cross-linked adducts between two guanines, which did not exceed 5% each of the products formed. Both the cis and trans isomers formed a G3-G15 platinum chelate, and the second also formed bis-chelates at both ends of the G-quadruplex structure: G3-GI5/G9-G21 and G3-GI5/G9-G24. The rMD simulations showed that the cross-linking reactions by the trans complex can occur without disturbing the stacking of the three G-quartets.
机译:端粒序列(T 2G4)4在含50 mM LiClO4,NaClO4或KClO4的水溶液中铂化。与[Pt(NH3)3(H20)r +反应的鸟嘌呤的鉴定表明,在三个阳离子的存在下存在相同类型的折叠,并且后者按顺序确定了G-四链体结构的相对稳定性。 K +> Na +?李+。三胺配合物产生约。 40-90%的单铂和多铂加合物与序列中16个鸟嘌呤中的4个鸟嘌呤结合,其递减量G9> G 15? G3> G21。这些加合物的形成可以用通过约束分子动力学(rMD)模拟获得的G-四链体结构来解释,这证实了Williamson等人提出的示意​​性模型。 [(1989)Cell 59,871-880]。双功能复合物顺式和反式-[Pt(NH3)2(H20)2r +]也首先与G9和G15反应,并在两个鸟嘌呤之间产生交联的加合物,每种形成的产物均不超过5%。顺式和反式异构体均形成G3-G15铂螯合物,第二个也在G-四链体结构的两端分别形成双螯合物:G3-GI5 / G9-G21和G3-GI5 / G9-G24。 rMD模拟表明反式配合物可以发生交联反应,而不会干扰三个G四元组的堆积。

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