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Competitive Binding Sites of a Ruthenium Arene Anticancer Complex on Oligonucleotides Studied by Mass Spectrometry: Ladder-Sequencing versus Top-Down

文献类型:期刊论文

作者Wu, Kui1; Hu, Wenbing1; Luo, Qun1; Li, Xianchan1; Xiong, Shaoxiang1; Sadler, Peter J.2; Wang, Fuyi1
刊名JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
出版日期2013-03-01
卷号24期号:3页码:410-420
关键词Mass Spectrometry Ladder-sequencing/top-down Ruthenium Anticancer Complexes Thymine/guanine Dna Oligonucleotide Binding Sites
ISSN号1044-0305
DOI10.1007/s13361-012-0539-z
英文摘要We report identification of the binding sites for an organometallic ruthenium anticancer complex [(eta (6)-biphenyl)Ru(en)Cl][PF6] (1; en = ethylenediamine) on the 15-mer single-stranded oligodeoxynucleotides (ODNs), 5'-CTCTCTX(7)G(8)Y(9)CTTCTC-3' [X = Y = T (I); X = C and Y = A (II); X = A and Y = T (III); X = T and Y = A (IV)] by electrospray ionization mass spectrometry (ESI-MS) in conjunction with enzymatic digestion or tandem mass spectrometry (top-down MS). ESI-MS combined with enzymatic digestion (termed MS-based ladder-sequencing), is effective for identification of the thermodynamically-favored G-binding sites, but not applicable to determine the thermodynamically unstable T-binding sites because the T-bound adducts dissociate during enzymatic digestion. In contrast, top-down MS is efficient for localization of the T binding sites, but not suitable for mapping ruthenated G bases, due to the facile fragmentation of G bases from ODN backbones prior to the dissociation of the phosphodiester bonds. The combination of the two MS approaches reveals that G(8) in each ODN is the preferred binding site for 1, and that the T binding sites of 1 are either T-7 or T-11 on I and IV, and either T-6 or T-11 on II and III, respectively. These findings not only demonstrate for the first time that T-bases in single-stranded oligonucleotides are kinetically competitive with guanine for such organoruthenium complexes, but also illustrate the relative merits of the combination of ladder-sequencing and top-down MS approaches to elucidate the interactions of metal anticancer complexes with DNA.
语种英语
WOS记录号WOS:000315515700013
出版者SPRINGER
源URL[http://ir.iccas.ac.cn/handle/121111/46567]  
专题中国科学院化学研究所
通讯作者Sadler, Peter J.
作者单位1.Chinese Acad Sci, Beijing Natl Lab Mol Sci, CAS Key Lab Analyt Chem Living Biosyst, Beijing Ctr Mass Spectrometry,Inst Chem, Beijing, Peoples R China
2.Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England
推荐引用方式
GB/T 7714
Wu, Kui,Hu, Wenbing,Luo, Qun,et al. Competitive Binding Sites of a Ruthenium Arene Anticancer Complex on Oligonucleotides Studied by Mass Spectrometry: Ladder-Sequencing versus Top-Down[J]. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY,2013,24(3):410-420.
APA Wu, Kui.,Hu, Wenbing.,Luo, Qun.,Li, Xianchan.,Xiong, Shaoxiang.,...&Wang, Fuyi.(2013).Competitive Binding Sites of a Ruthenium Arene Anticancer Complex on Oligonucleotides Studied by Mass Spectrometry: Ladder-Sequencing versus Top-Down.JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY,24(3),410-420.
MLA Wu, Kui,et al."Competitive Binding Sites of a Ruthenium Arene Anticancer Complex on Oligonucleotides Studied by Mass Spectrometry: Ladder-Sequencing versus Top-Down".JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 24.3(2013):410-420.

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来源:化学研究所

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