中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Thymines in Single-Stranded Oligonucleotides and G-Quadruplex DNA Are Competitive with Guanines for Binding to an Organoruthenium Anticancer Complex

文献类型:期刊论文

作者Wu, Kui1,2; Liu, Suyan1,2; Luo, Qun1,2; Hu, Wenbing1,2; Li, Xianchan1,2; Wang, Fuyi1,2; Zheng, Renhui1,3; Cui, Jie1; Sadler, Peter J.4; Xiang, Junfeng1
刊名INORGANIC CHEMISTRY
出版日期2013-10-07
卷号52期号:19页码:11332-11342
ISSN号0020-1669
DOI10.1021/ic401606v
英文摘要Organometallic ruthenium(II) complexes [(eta(6)-arene)-Ru(en)Cl](+) (arene = e.g., biphenyl (1), dihydrophenanthrene, tetrahydroanthracene) show promising anticancer activity both in vitro and in vivo and are cytotoxic to cisplatin-resistant cancer cells, implying that these monofunctional complexes have a different mechanism of action from that of bifunctional cisplatin. We demonstrate here that complex 1 binds selectively to the guanine base in the 15-mer single-stranded oligodeoxynucleotides (ODNs) 5'-CTCTCTX(7)G(8)Y(9)CTTCTC-3' [X = Y = T; X = C, Y = A; X = A, Y = T; X = T, Y = A] to form thermodynamically stable adducts, but thymine bases (T-7/T-11 or T-6/T-11) compete kinetically with guanine for binding to 1. The T-bound monoruthenated species eventually convert to diruthenated products via a second step of binding at G or/and to G-bound monoruthenated species through dissociation of the diruthenated adducts. Complex 1 was further shown to bind preferentially to the middle T in a sequence rather than to a T near the terminus and favor coordination to a 5'-T compared to a 3'-T. Interestingly, the T bases in the human telomeric G-quadruplex sequence (5'-AGGGTTAGGGTTAGGGTTAGGG-3') were found to be more competitive both kinetically and thermodynamically with G bases for binding to 1. These results suggest that thymine bases play a unique role in the pathways of ruthenation of DNA by organoruthenium anticancer complexes and illustrate that kinetic studies can provide new insight into the mechanism of action of metallodrugs in addition to study of the structures and functions of the thermodynamically stable end products.
语种英语
WOS记录号WOS:000326319800076
出版者AMER CHEMICAL SOC
源URL[http://ir.iccas.ac.cn/handle/121111/42235]  
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, Beijing Natl Lab Mol Sci, Beijing 100190, Peoples R China
2.Beijing Ctr Mass Spectrometry, CAS Key Lab Analyt Chem Living Biosyst, Beijing 100190, Peoples R China
3.State Key Lab Struct Chem Unstable & Stable Speci, Beijing 100190, Peoples R China
4.Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England
推荐引用方式
GB/T 7714
Wu, Kui,Liu, Suyan,Luo, Qun,et al. Thymines in Single-Stranded Oligonucleotides and G-Quadruplex DNA Are Competitive with Guanines for Binding to an Organoruthenium Anticancer Complex[J]. INORGANIC CHEMISTRY,2013,52(19):11332-11342.
APA Wu, Kui.,Liu, Suyan.,Luo, Qun.,Hu, Wenbing.,Li, Xianchan.,...&Xiong, Shaoxiang.(2013).Thymines in Single-Stranded Oligonucleotides and G-Quadruplex DNA Are Competitive with Guanines for Binding to an Organoruthenium Anticancer Complex.INORGANIC CHEMISTRY,52(19),11332-11342.
MLA Wu, Kui,et al."Thymines in Single-Stranded Oligonucleotides and G-Quadruplex DNA Are Competitive with Guanines for Binding to an Organoruthenium Anticancer Complex".INORGANIC CHEMISTRY 52.19(2013):11332-11342.

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来源:化学研究所

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