Mechanism of interstrand migration of organoruthenium anticancer complexes within a DNA duplex
文献类型：期刊论文
| 作者 | Wu, Kui1,2; Luo, Qun1,2; Hu, Wenbing1,2; Li, Xianchan1,2; Wang, Fuyi1,2; Xiong, Shaoxiang1,2; Sadler, Peter J.3 |
| 刊名 | METALLOMICS
 |
| 出版日期 | 2012 |
| 卷号 | 4期号:2页码:139-148 |
| ISSN号 | 1756-5901 |
| DOI | 10.1039/c2mt00162d |
| 英文摘要 | Organometallic ruthenium(II) anticancer complexes [(eta(6)-arene)Ru(en)Cl][PF6] (e.g. arene = biphenyl (bip, 1), indane (ind, 2); en = ethylenediamine) bind to N7 of guanine (G) in DNA selectively. The fragment {(eta(6)-bip)Ru(en)}(2+) (1') bound to N7 of one guanine residue at a 14-mer duplex DNA migrates readily to other guanine residues in both the same strand and the complementary strand when the strands are hybridized at elevated temperature. In this work, by applying HPLC coupled to mass spectrometry, the mechanism of such intra- and interstrand migration was investigated using a 15-mer duplex, in which one strand 5'-CTCTCTTG(8)TCTTCTC-3' (I) contained a single guanine (G(8)). The results show that the interstrand migration of complexes 1 and 2 within the duplex involves an SN1 pathway, firstly solvent-assisted dissociation of the initially G(8)-bound adducts I-G(8)-1' and I-G(8)-2' (2' = {(eta(6)-ind)Ru(en)}(2+)) as the rate-controlling step, and secondly the coordination of the dissociated 1' and 2' to guanine bases (G(21) for 1', either G(21) or G(18) for 2') on strand II. The high temperature used to anneal the single strands was found to increase the migration rate. The formation of the duplex acts as a key driving force to promote the dissociation of G(8)-bound 1' and 2' due to the competition of cytosine in II with the en-NH2 groups in 1' and 2' for H-bonding with C6O of guanine. Complex 2 (t(1/2) = 18 h) containing a mono-ringed arene ligand dissociates more readily from the initially binding site G(8) than complex 1 (t(1/2) = 23 h). The extended biphenyl arene ligand which is intercalated into DNA stabilizes the adduct I-G(8)-1'. These results provide new insight into this unusual metal migration, and are of significance for the design and development of more active organometallic ruthenium anticancer complexes. |
| 语种 | 英语 |
| WOS记录号 | WOS:000299793800002 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/49369]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Wang, Fuyi |
| 作者单位 | 1.Chinese Acad Sci, Inst Chem, CAS Key Lab Analyt Chem Living Biosyst, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Inst Chem, Beijing Natl Lab Mol Sci, Beijing 100190, Peoples R China 3.Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England |
| 推荐引用方式 GB/T 7714 | Wu, Kui,Luo, Qun,Hu, Wenbing,et al. Mechanism of interstrand migration of organoruthenium anticancer complexes within a DNA duplex[J]. METALLOMICS,2012,4(2):139-148. |
| APA | Wu, Kui.,Luo, Qun.,Hu, Wenbing.,Li, Xianchan.,Wang, Fuyi.,...&Sadler, Peter J..(2012).Mechanism of interstrand migration of organoruthenium anticancer complexes within a DNA duplex.METALLOMICS,4(2),139-148. |
| MLA | Wu, Kui,et al."Mechanism of interstrand migration of organoruthenium anticancer complexes within a DNA duplex".METALLOMICS 4.2(2012):139-148. |
入库方式： OAI收割
来源：化学研究所
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