Competition between glutathione and DNA oligonucleotides for ruthenium(II) arene anticancer complexes
文献类型：期刊论文
| 作者 | Wang, Fuyi1,2; Xu, Jingjing2; Wu, Kui1; Weidt, Stefan K.2; Mackay, C. Logan2; Langridge-Smith, Pat R. R.2; Sadler, Peter J.3 |
| 刊名 | DALTON TRANSACTIONS
 |
| 出版日期 | 2013 |
| 卷号 | 42期号:9页码:3188-3195 |
| ISSN号 | 1477-9226 |
| DOI | 10.1039/c2dt32091f |
| 英文摘要 | The organometallic anticancer complex [(eta(6)-bip)Ru(en)Cl](+) (1; bip = biphenyl, en = ethylenediamine) selectively binds to N7 of guanine bases of oligonucleotides and native DNA. However, under physiologically relevant conditions (micromolar Ru concentrations, pH 7, 22 mM NaCl, 310 K), the tripeptide glutathione (gamma-L-Glu-L-Cys-Gly; GSH) is kinetically competitive with guanine (as guanosine 3',5'-cyclic monophosphate, cGMP) for coordination with complex 1, and gives rise to a ruthenium thiolato adduct. This thiolato adduct can subsequently undergo oxidation to a sulfenate intermediate, providing a facile route for the formation of a final cGMP adduct via the displacement of S-bound glutathione by G N7 (F. Y. Wang, J. J. Xu, A. Habtemariam, J. Bella and P. J. Sadler, J. Am. Chem. Soc., 2005, 127, 17734). In this work, the competition between GSH and the single-stranded 14-mer oligonucleotide 5'-TATGTACCATGTAT-3' (I) and duplex III (III = I + II, II = 5'-ATACATGGTACATA) for complex 1 and its analogue [(eta(6)-tha)Ru(en)Cl](+) (2, tha = tetrahydroanthracene) under physiologically relevant conditions was investigated using conventional ESI-MS and high resolution ESI-FTICR-MS coupled to conventional HPLC and nanoscale HPLC, respectively. The results indicate that whether there was high excess of GSH or not in the reaction mixtures, the reaction of complex 1 or 2 with single-stranded oligonucleotide I always gave rise to mono-ruthenated oligonucleotide, and the reaction of complex 1 or 2 with duplex III gave rise to the mono-ruthenated duplex oligonucleotide. Furthermore, the ruthenation of duplex III by complex 1 showed no significant discrimination between the complementary strands I and II, but complex 2 appeared to bind preferentially to strand II compared to strand I as revealed by the high resolution FTICR-MS analysis. GSH is highly abundant in cells at millimolar concentrations and is well known to be involved in the deactivation of the clinical drug cisplatin and in platinum resistance. Our findings reveal a potentially contrasting role for GSH in the mechanism of action of these ruthenium anticancer complexes that may contribute to the lack of cross-resistance with platinum drugs. |
| 语种 | 英语 |
| WOS记录号 | WOS:000314608700020 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/54555]  |
| 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, Inst Chem, CAS Key Lab Analyt Chem Living Biosyst, Beijing Natl Lab Mol Sci, Beijing 100190, Peoples R China 2.Univ Edinburgh, Sch Chem, SIRCAMS, Edinburgh EH9 3JJ, Midlothian, Scotland 3.Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England |
| 推荐引用方式 GB/T 7714 | Wang, Fuyi,Xu, Jingjing,Wu, Kui,et al. Competition between glutathione and DNA oligonucleotides for ruthenium(II) arene anticancer complexes[J]. DALTON TRANSACTIONS,2013,42(9):3188-3195. |
| APA | Wang, Fuyi.,Xu, Jingjing.,Wu, Kui.,Weidt, Stefan K..,Mackay, C. Logan.,...&Sadler, Peter J..(2013).Competition between glutathione and DNA oligonucleotides for ruthenium(II) arene anticancer complexes.DALTON TRANSACTIONS,42(9),3188-3195. |
| MLA | Wang, Fuyi,et al."Competition between glutathione and DNA oligonucleotides for ruthenium(II) arene anticancer complexes".DALTON TRANSACTIONS 42.9(2013):3188-3195. |
入库方式： OAI收割
来源：化学研究所
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