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Photocontrolled DNA binding of a receptor-targeted organometallic ruthenium(II) complex
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Barragán, Flavia, López-Senín, Paula, Salassa, Luca, Betanzos-Lara, Soledad, Habtemariam, Abraha, Moreno, Virtudes, Sadler, P. J. and Marchán, Vicente (2011) Photocontrolled DNA binding of a receptor-targeted organometallic ruthenium(II) complex. Journal of the American Chemical Society, Vol.133 (No.35). pp. 14098-14108. doi:10.1021/ja205235m ISSN 0002-7863.
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Official URL: http://dx.doi.org/10.1021/ja205235m
Abstract
A photoactivated ruthenium(II) arene complex has been conjugated to two receptor-binding peptides, a dicarba analogue of octreotide and the Arg-Gly-Asp (RGD) tripeptide. These peptides can act as “tumor-targeting devices” since their receptors are overexpressed on the membranes of tumor cells. Both ruthenium–peptide conjugates are stable in aqueous solution in the dark, but upon irradiation with visible light, the pyridyl-derivatized peptides were selectively photodissociated from the ruthenium complex, as inferred by UV–vis and NMR spectroscopy. Importantly, the reactive aqua species generated from the conjugates, [(η6-p-cym)Ru(bpm)(H2O)]2+, reacted with the model DNA nucleobase 9-ethylguanine as well as with guanines of two DNA sequences, 5′dCATGGCT and 5′dAGCCATG. Interestingly, when irradiation was performed in the presence of the oligonucleotides, a new ruthenium adduct involving both guanines was formed as a consequence of the photodriven loss of p-cymene from the two monofunctional adducts. The release of the arene ligand and the formation of a ruthenated product with a multidentate binding mode might have important implications for the biological activity of such photoactivated ruthenium(II) arene complexes. Finally, photoreactions with the peptide–oligonucleotide hybrid, Phac-His-Gly-Met-linker-p5′dCATGGCT, also led to arene release and to guanine adducts, including a GG chelate. The lack of interaction with the peptide fragment confirms the preference of such organometallic ruthenium(II) complexes for guanine over other potential biological ligands, such as histidine or methionine amino acids.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||
Library of Congress Subject Headings (LCSH): | Ruthenium, Aromatic compounds, Organometallic compounds -- Therapeutic use, Photochemistry, Cisplatin, Antineoplastic agents -- Development, DNA-drug interactions | ||||
Journal or Publication Title: | Journal of the American Chemical Society | ||||
Publisher: | American Chemical Society | ||||
ISSN: | 0002-7863 | ||||
Official Date: | 2011 | ||||
Dates: |
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Volume: | Vol.133 | ||||
Number: | No.35 | ||||
Number of Pages: | 11 | ||||
Page Range: | pp. 14098-14108 | ||||
DOI: | 10.1021/ja205235m | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Date of first compliant deposit: | 18 December 2015 | ||||
Date of first compliant Open Access: | 18 December 2015 | ||||
Funder: | Spain. Ministerio de Educación y Ciencia (MEC), Catalonia (Spain), Seventh Framework Programme (European Commission) (FP7) | ||||
Grant number: | CTQ2005-01834 (MEC), CTQ2007-68014 (MEC), CTQ2008-02064 (MEC), CTQ2010-21567 (MEC), 2009SGR208 (Catalonia), 247450 (ERC), 220281 (FP7) |
Data sourced from Thomson Reuters' Web of Knowledge
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