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首页> 外文期刊>Journal of Molecular Biology >NMR solution structure of an oxaliplatin 1,2-d(GG) intrastrand cross-link in a DNA dodecamer duplex
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NMR solution structure of an oxaliplatin 1,2-d(GG) intrastrand cross-link in a DNA dodecamer duplex

机译：DNA dodecamer双链体中奥沙利铂1,2-d（GG）内链交联的NMR溶液结构

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摘要

We have determined, at high resolution, the NMF; solution structure of an oxaliplatin-GG DNA dodecamer in the A (G) under bar(G) under barC sequence context by 2D NMR studies. Homonuclear assignment strategies resulted in unambiguous assignment of 203 out of 249 protons, which corresponds to assignment of similar to81% of the protons. Assignments of H5' and H5" protons were tentative due to resonance overlap. The structure of the oxaliplatin duplex was calculated using the program CNS with a simulated annealing protocol. A total of 510 experimental restraints were employed in the structure calculation. Of 20 calculated structures, the 15 with the lowest energy were accepted. as a family. The RMSD of the 15 lowest energy structures was 0.68 Angstrom, indicating good structural convergence. The theoretical NOESY spectrum obtained by back-calculation from the final average structure showed excellent agreement with the experimental data, indicating that the final structure was in good agreement with the experimental NMR data. Significant conformational differences were observed between the oxaliplatin-GG 12-mer DNA we studied and all previous solution structures of cisplatin-GG DNA duplexes. For example, the oxaliplatin-GG adduct shows much less distortion at the A (G) under bar base-pair step than the cisplatin-GG adducts. In addition, the oxaliplatin-GG structure also has a narrow minor groove and an overall axis bend of about 31degrees, both of which are very different from the recent NMR structures for the cisplatin-GG adducts. These structural differences may explain some of the biological differences between oxaliplatin- and cisplatin-GG adducts. (C) 2004 Elsevier Ltd. All rights reserved.
机译：我们已经高分辨率确定了NMF; 2D NMR研究在barC序列背景下bar（G）下A（G）中奥沙利铂-GG DNA十二聚体的溶液结构。同源核分配策略导致249个质子中的203个明确分配，这对应于约81％的质子分配。由于共振重叠，H5'和H5“质子的分配暂定。使用具有模拟退火方案的CNS程序，计算了奥沙利铂双链体的结构。在结构计算中总共使用了510个实验约束。计算出20个结构，我们接受了能量最低的15个分子作为一个族，能量最低的15个结构的RMSD为0.68埃，表明具有良好的结构收敛性，通过最终平均结构的反算获得的理论NOESY光谱与该结构具有很好的一致性。实验数据表明最终结构与实验NMR数据吻合良好，我们研究的奥沙利铂-GG 12-mer DNA与以前的顺铂-GG DNA双链体溶液结构之间均存在明显的构象差异。奥沙利铂-GG加合物在棒碱基对步骤下在A（G）处的变形要比顺铂-GG加成少得多cts。此外，奥沙利铂-GG结构还具有较窄的小凹槽和约31度的总轴弯曲度，两者均与最近的顺铂-GG加合物的NMR结构有很大不同。这些结构差异可以解释奥沙利铂-和顺铂-GG加合物之间的某些生物学差异。 （C）2004 Elsevier Ltd.保留所有权利。

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