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 |
DOI | 10.1021/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. |
入库方式: OAI收割
来源:化学研究所
浏览0
下载0
收藏0
其他版本
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。