ICCAS OpenIR
Penetrative DNA intercalation and G-base selectivity of an organometallic tetrahydroanthracene Ru-II anticancer complex
Liu, Hong-Ke1; Parkinson, John A.3; Bella, Juraj5; Wang, Fuyi4; Sadler, Peter J.2
2010
Source PublicationCHEMICAL SCIENCE
ISSN2041-6520
Volume1Issue:2Pages:258-270
AbstractThe organometallic Ru-II arene complex [(eta(6)-tha) Ru(en)Cl](+) (1), where tha tetrahydroanthracene and en = ethylenediamine, is potently cytotoxic towards cancer cells. We have used a combination of HPLC, ESI-MS, 1D- and 2D-NMR, including [H-1, H-1] ROESY, NOESY, [H-1, N-15] HSQC (using N-15-1), and [H-1, P-31] experiments to elucidate the role of the non-aromatic, bulky rings of tha in adducts with the DNA hexamer d(CGGCCG), since DNA is a potential target for this drug. Reactions of 1 with single-stranded d(CGGCCG) gave rise to ruthenation at each of the three G bases, whereas reactions of the duplex d(CGGCCG)(2) with 1 mol equiv. 1 led to exclusive ruthenation of G(3) and G(6) (and G(9), G(12)) and not G(2) (or G(8)). Addition of a second mol equiv. of 1 gave di-ruthenated adducts (major sites G(3)/G(6), G(6)/G(9), G(2)/G(6)), and on reaction with a third mol equiv. tri-ruthenation (G(2), G(3)/G(6)/G(12)). The NMR data are indicative of the coordinative binding of Ru-tha specifically to G(3) and G(6), together with penetrative intercalation of the bulky non-coordinated tha rings B and C of 1', selectively between two base pairs G(3)/C-10:C-4/G(9) and G(6)/C-7:C-5/G(8). Intercalation at GpC base steps by tha has a lower energy penalty compared to intercalation at GpG base steps, thereby allowing accommodation of tha. Mono-intercalation of tha reduced the strength of H-bonding between en-NH and GO6. These differences in structural distortions compared to cisplatin induced by the coordinative binding of Ru-tha to GN7 may contribute to the differences in mechanism of action, including protein recognition of the metallated lesions, and lack of cross resistance.
DOI10.1039/c0sc00175a
Indexed BySCI
Language英语
WOS IDWOS:000281436100017
PublisherROYAL SOC CHEMISTRY
Citation statistics
Cited Times:48[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.iccas.ac.cn/handle/121111/71268
Collection中国科学院化学研究所
Corresponding AuthorLiu, Hong-Ke
Affiliation1.Nanjing Normal Univ, Jiangsu Key Lab Biofunct Mat, Sch Chem, Nanjing, Peoples R China
2.Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England
3.Univ Strathclyde, WestCHEM Dept Pure & Appl Chem, Glasgow G1 1XL, Lanark, Scotland
4.Chinese Acad Sci, Beijing Natl Lab Mol Sci, Inst Chem, Beijing 100190, Peoples R China
5.Univ Edinburgh, Sch Chem, Edinburgh EH9 3JJ, Midlothian, Scotland
Recommended Citation
GB/T 7714
Liu, Hong-Ke,Parkinson, John A.,Bella, Juraj,et al. Penetrative DNA intercalation and G-base selectivity of an organometallic tetrahydroanthracene Ru-II anticancer complex[J]. CHEMICAL SCIENCE,2010,1(2):258-270.
APA Liu, Hong-Ke,Parkinson, John A.,Bella, Juraj,Wang, Fuyi,&Sadler, Peter J..(2010).Penetrative DNA intercalation and G-base selectivity of an organometallic tetrahydroanthracene Ru-II anticancer complex.CHEMICAL SCIENCE,1(2),258-270.
MLA Liu, Hong-Ke,et al."Penetrative DNA intercalation and G-base selectivity of an organometallic tetrahydroanthracene Ru-II anticancer complex".CHEMICAL SCIENCE 1.2(2010):258-270.
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