期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 133, 期 35, 页码 14098-14108出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja205235m
关键词
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资金
- Ministerio de Educacion y Ciencia [CTQ2005-01834, CTQ2007-68014, CTQ2008-02064, CTQ2010-21567]
- Generalitat de Catalunya [2009SGR208]
- Programa d'Intensificacio de la Recerca (UB)
- European Community [220281]
- ERC BIOINCMED [247450]
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, [(eta(6)-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-P(5')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.
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