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首页> 外文期刊>Inorganic Chemistry: A Research Journal that Includes Bioinorganic, Catalytic, Organometallic, Solid-State, and Synthetic Chemistry and Reaction Dynamics >Cisplatin (cis-Pt(NH3)(2)Cl-2) and cis-[Pt(NH3)(2)(H2O)(2)](2+) intrastrand cross-linking reactions at the telomere GGGT DNA sequence embedded in a duplex, a hairpin, and a bulged duplex: Use of Mg2+ and Zn2+ to convert a hairpin to a bulged duplex
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Cisplatin (cis-Pt(NH3)(2)Cl-2) and cis-[Pt(NH3)(2)(H2O)(2)](2+) intrastrand cross-linking reactions at the telomere GGGT DNA sequence embedded in a duplex, a hairpin, and a bulged duplex: Use of Mg2+ and Zn2+ to convert a hairpin to a bulged duplex

机译：顺铂（cis-Pt（NH3）（2）Cl-2）和cis- [Pt（NH3）（2）（H2O）（2）]（2+）链内交联反应在端粒GGGT DNA序列中嵌入双链体，发夹和凸起的双链体：使用Mg2 +和Zn2 +将发夹转变为凸起的双链体

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In the past, we showed that metal species have a high affinity fur the central G in the GGG sequence of the duplex d(A(1)T(2)G(3)G(4)G(5)T(6)A(7)C(8)C(9)C(10)A(11)T(12))(2) (G3-D) and that cisplatin (cis-Pt(NH3)(2)Cl-2) and G3-D formed an N7-Pt-N7 G(4),G(5) intrastrand cross-link preferentially over the G(3),G(4) adduct (similar to 25:1). Thus, a putative G(4) monoadduct was postulated to cross-link in the 3'- rather than the normally more favorable 5'-direction. To evaluate this hypothesis and also to explore why the G3-D G(4),G(5) adduct had atl unusual hairpin structure, we have now introduced the use of N,N'-dimethylthiourea (DMTU) as a monoadduct trap and have extended the study to a G3-D analogue with a hairpin form, d(A(1)T(2)G(3)G(4)G(5)T(6)T(7)C(8)C(9)C(10)A(11)T(12)) (G3-H). Chemical shift and 2D H-1 and C-13 NMR data indicated that the G3-H hairpin has a stem region with B-form structure and a nonhelical loop region. Zn2+ or Mg2+ ions transformed G3-H into a bulged duplex. Downfield shifts of G(4)H(8) and G(4)C(8) NMR signals indicated that Zn2+ binds preferentially to G(4)N7. Reaction of cisplatin or cis-[Pt(NH3)(2)(H2O)(2)](2+) with the bulged duplex and hairpin forms of G3-H gave a similar intrastrand cross-link ratio, G(4),G(5):G(3),G(4) = 7:3. This ratio is insensitive to DNA form or Pt leaving group. For G3-D this ratio is lower in the cis- [Pt(NH3)(2)(H2O)(2)](2+) reaction (similar to 1:1) than in the cisplatin reaction (25:1), indicating that the leaving group influences the cross-linking step for G3-D. The G(4) monoadducts of the cis-Pt(NH3)(2)Cl-2-G3-H and -G3-D and the cis-[Pt(NH3)(2)(H2O)(2)](2+)-G3-D reactions were trapped with DMTU, but no monoadduct was trapped in the cis- [Pt(NH3)(2)(H2O)(2)](2+)-G3-H reaction. The results suggest that the respective monoadducts are more long-lived for G3-D. We postulate that the G(5) in the G3-D Cl-G(4) monoadduct is placed in a favorable position to form the cross-link because of a prior conformational change induced by G(4)-A(7) stacking. This accounts for the very high selectivity for 3'-cross-linking. Nevertheless, in all other cases, regardless of the form or conformation, 3'-direction cross-linking is unusually favored at GGGT sequences, suggesting that the sequence itself contributes greatly to the 3'-cross-linking preference; since telomeres have multiple repeats of this GGGT sequence, this finding may have biological relevance. [References: 71]
机译：过去，我们表明金属物种对双链体d（A（1）T（2）G（3）G（4）G（5）T（6）的GGG序列中的中心G具有高亲和力A（7）C（8）C（9）C（10）A（11）T（12））（2）（G3-D）和顺铂（cis-Pt（NH3）（2）Cl-2） G3-D优先于G（3），G（4）加合物形成N7-Pt-N7 G（4），G（5）内链交联（类似于25：1）。因此，假定一个假定的G（4）单加合物在3'-交联而不是通常更有利的5'-方向交联。为了评估此假设并探讨G3-D G（4），G（5）加合物为何具有不寻常的发夹结构，我们现在介绍了使用N，N'-二甲基硫脲（DMTU）作为单加合物捕集剂和已将研究扩展到发夹形式的G3-D类似物d（A（1）T（2）G（3）G（4）G（5）T（6）T（7）C（8）C （9）C（10）A（11）T（12））（G3-H）。化学位移和2 H-1和C-13 NMR数据表明，G3-H发夹具有带B型结构的茎区域和非螺旋环区域。 Zn2 +或Mg2 +离子将G3-H转化为凸起的双链体。 G（4）H（8）和G（4）C（8）NMR信号的场下偏移表明Zn2 +优先结合G（4）N7。顺铂或顺式[Pt（NH3）（2）（H2O）（2）]（2+）与凸出的双链体和发夹形式的G3-H反应得到相似的链内交联比G（4）， G（5）：G（3），G（4）= 7：3。该比例对DNA形式或Pt离去基团不敏感。对于G3-D，该比率在顺-[Pt（NH3）（2）（H2O）（2）]（2+）反应（类似于1：1）中比在顺铂反应（25：1）中更低，表示离去基团影响G3-D的交联步骤。顺式-Pt（NH3）（2）Cl-2-G3-H和-G3-D与顺式-[Pt（NH3）（2）（H2O）（2）]（2）的G（4）单加合物+）-G3-D反应用DMTU捕获，但顺式[Pt（NH3）（2）（H2O）（2）]（2 +）-G3-H反应中没有捕获单加合物。结果表明，对于G3-D，各个单加合物的寿命更长。我们假设G3-D Cl-G（4）单加合物中的G（5）处于有利位置以形成交联，这是由于G（4）-A（7）堆积引起的先前构象变化。这说明了3'-交联的非常高的选择性。然而，在所有其他情况下，无论是何种形式或构象，GGGT序列都异常偏爱3'方向交联，这表明该序列本身对3'交联偏好做出了巨大贡献。由于端粒具有该GGGT序列的多个重复，因此该发现可能具有生物学意义。 [参考：71]

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