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首页> 外文期刊>Biochemistry >Cross-links of quadruplex structures from human telomeric DNA by dinuclear platinum complexes show the flexibility of both structures
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Cross-links of quadruplex structures from human telomeric DNA by dinuclear platinum complexes show the flexibility of both structures

机译：双核铂配合物与人端粒DNA四链体结构的交联显示两种结构的灵活性

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The folding of AG(3)(T(2)AG(3))(3) was investigated in the presence of Na+ or K+ ions, by using the dinuclear platinum complexes [{trans-PtCl(NH3)(2)}(2)H2N(CH2)(n)NH2]Cl-2 (n = 2 or 6). AG(3)(T(2)AG(3))(3) has been previously found to adopt two different quadruplex structures: the antiparallel one in a solution containing Na+ and the parallel one in a K+-containing crystal. The two structures are strikingly distinct and are not expected to form the same platinum cross-links. Therefore, characterization of the cross-links formed with platinum complexes in solution allowed the predominant conformation(s) to be identified. The bases coordinating the platinum atoms were identified by chemical and 3'-exonuclease digestions. The observed cross-links showed that the parallel structure exists in solution whatever the cation and confirmed the existence of the antiparallel structure in the presence of both cations as previously reported from cross-linking experiments of AG(3)(T(2)AG(3))(3) by mononuclear platinum complexes. Furthermore, the major platinum cross-links were unexpectedly formed between two guanines belonging to the same G-quartet. Their formation was rationalized using molecular dynamics simulations in implicit solvent of the two quadruplex structures. It was shown that they were flexible, allowing some guanines to leave reversibly the top G-quartet and thus rendering their N-7 atom accessible to platinum complexes. Our results also suggest that the human telomere sequence could be a target for such platinum complexes.
机译：通过使用双核铂配合物[{trans-PtCl（NH3）（2）}（），在Na +或K +离子存在下研究了AG（3）（T（2）AG（3））（3）的折叠2）H2N（CH2）（n）NH2] Cl-2（n = 2或6）。以前已经发现AG（3）（T（2）AG（3））（3）采用两种不同的四重结构：在含有Na +的溶液中反平行的一种和在含有K +的晶体中平行的一种。两种结构截然不同，并且预期不会形成相同的铂交联。因此，在溶液中与铂络合物形成的交联的表征使得可以鉴定主要构象。通过化学和3'-核酸外切酶消化鉴定配位铂原子的碱基。观察到的交联表明，无论阳离子如何，溶液中均存在平行结构，并证实了这两种阳离子均存在反平行结构，如先前从AG（3）（T（2）AG（ 3））（3）的单核铂络合物。此外，主要的铂交联意外地在属于同一G四重奏的两个鸟嘌呤之间形成。使用分子动力学模拟在两个四链体结构的隐式溶剂中合理化了它们的形成。结果表明它们具有柔韧性，可以使一些鸟嘌呤可逆地离开顶部的G四重峰，从而使它们的N-7原子可与铂络合物接触。我们的结果还表明，人端粒序列可能是此类铂配合物的靶标。

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