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Title: | Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) Complex |
Author: | Barragán, Flavia López-Senín, Paula Salassa, Luca Betanzos-Lara, Soledad Habtemariam, Abraha Moreno Martínez, Virtudes Sadler, Peter Marchán Sancho, Vicente |
Keywords: | Quimioteràpia del càncer Pèptids Ruteni Oligonucleòtids Receptors cel·lulars Cancer chemotherapy Peptides Ruthenium Oligonucleotides Cell receptors |
Issue Date: | 2011 |
Publisher: | American Chemical Society |
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. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1021/ja205235m |
It is part of: | Journal of the American Chemical Society, 2011, vol. 133, num. 35, p. 14098-14108 |
URI: | http://hdl.handle.net/2445/44124 |
Related resource: | http://dx.doi.org/10.1021/ja205235m |
ISSN: | 0002-7863 |
Appears in Collections: | Articles publicats en revistes (Química Inorgànica i Orgànica) Publicacions de projectes de recerca finançats per la UE |
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File | Description | Size | Format | |
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599372.pdf | 1.69 MB | Adobe PDF | View/Open |
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