Insertion of a bulky rhodium complex into a DNA cytosine-cytosine mismatch: An NMR solution study
Insertion of a bulky rhodium complex into a DNA cytosine-cytosine mismatch: An NMR solution study
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DOI：
10.1021/ja0739436
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发表时间：
2007-10-10
影响因子：
15
通讯作者：
Barton, Jacqueline K.
中科院分区：
文献类型：
--
作者：
Cordier, Christine;Pierre, Valerie C.;Barton, Jacqueline K.
体积庞大的八面体配合物Rh(bpy)(2)chrysi(3+) （chrysi = 5,6- chrysenequinonedi亚胺）在DNA双链中结合单碱基错配，具有微摩尔结合亲和力和高选择性。在这里，我们提出了一项核磁共振溶液研究，以表征这种庞大的金属配合物的结合模式，其靶CC在寡核苷酸双链（5 '-CGGACTCCG-3 '）中不匹配(2)。NOESY和COSY研究均表明，Rh(bPY)(2)chrysi（3+）通过小槽深入DNA错配位点，并将两种不稳定的胞嘧啶射入相反的大槽。插入只会最小程度地扭曲结合位点上的寡核苷酸的构象。两侧匹配良好的碱基对彼此保持紧密的氢键，2D DQF-COSY实验表明，所有糖都保持其原始的C-2 '-endo构象。值得注意的是，P-31核磁共振显示，从B-I构象到B-II构象的磷酸角打开足以插入大块的金属配合物。这些结果证实了晶体学上得到的结果，重要的是，为这种特定的插入模式在溶液中提供了结构证据。
The bulky octahedral complex Rh(bpy)(2)chrysi(3+) (chrysi = 5,6-chrysenequinonediimine) binds single-base mismatches in a DNA duplex with micromolar binding affinities and high selectivity. Here we present an NMR solution study to characterize the binding mode of this bulky metal complex with its target CC mismatch in the oligonucleotide duplex (5 '-CGGACTCCG-3 ')(2). Both NOESY and COSY studies indicate that Rh(bPY)(2)chrysi(3+) inserts deeply in the DNA at the mismatch site via the minor groove and with ejection of both destabilized cytosines into the opposite major groove. The insertion only minimally distorts the conformation of the oligonucleotide local to the binding site. Both flanking, well-matched base pairs remain tightly hydrogen-bonded to each other, and 2D DQF-COSY experiments indicate that all sugars maintain their original C-2 '-endo conformation. Remarkably, P-31 NMR reveals that opening of the phosphate angles from a B-I to a B-II conformation is sufficient for insertion of the bulky metal complex. These results corroborate those obtained crystallographically and, importantly, provide structural evidence for this specific insertion mode in solution.