Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) Complex

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 cel...

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Authors: Barragán, Flavia, López-Senín, Paula, Salassa, Luca, Betanzos-Lara, Soledad, Habtemariam, Abraha, Moreno Martínez, Virtudes, Sadler, Peter, Marchán Sancho, Vicente
Format: article
Status:Versión aceptada para publicación
Publication Date:2011
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/44124
Online Access:https://hdl.handle.net/2445/44124
Access Level:Open access
Keyword:Quimioteràpia del càncer
Pèptids
Ruteni
Oligonucleòtids
Receptors cel·lulars
Cancer chemotherapy
Peptides
Ruthenium
Oligonucleotides
Cell receptors
id ES_d178ea731be2afc2f08beed11bf3b1b9
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spelling Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) ComplexBarragán, FlaviaLópez-Senín, PaulaSalassa, LucaBetanzos-Lara, SoledadHabtemariam, AbrahaMoreno Martínez, VirtudesSadler, PeterMarchán Sancho, VicenteQuimioteràpia del càncerPèptidsRuteniOligonucleòtidsReceptors cel·lularsCancer chemotherapyPeptidesRutheniumOligonucleotidesCell receptorsA 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.American Chemical Society2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/44124Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: http://dx.doi.org/10.1021/ja205235mJournal of the American Chemical Society, 2011, vol. 133, num. 35, p. 14098-14108http://dx.doi.org/10.1021/ja205235minfo:eu-repo/grantAgreement/EC/FP7/220281info:eu-repo/grantAgreement/EC/FP7/247450(c) American Chemical Society , 2011info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/441242026-05-27T06:46:51Z
dc.title.none.fl_str_mv Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) Complex
title Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) Complex
spellingShingle Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) Complex
Barragán, Flavia
Quimioteràpia del càncer
Pèptids
Ruteni
Oligonucleòtids
Receptors cel·lulars
Cancer chemotherapy
Peptides
Ruthenium
Oligonucleotides
Cell receptors
title_short Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) Complex
title_full Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) Complex
title_fullStr Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) Complex
title_full_unstemmed Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) Complex
title_sort Photocontrolled DNA Binding of a Receptor-Targeted Organometallic Ruthenium(II) Complex
dc.creator.none.fl_str_mv Barragán, Flavia
López-Senín, Paula
Salassa, Luca
Betanzos-Lara, Soledad
Habtemariam, Abraha
Moreno Martínez, Virtudes
Sadler, Peter
Marchán Sancho, Vicente
author Barragán, Flavia
author_facet Barragán, Flavia
López-Senín, Paula
Salassa, Luca
Betanzos-Lara, Soledad
Habtemariam, Abraha
Moreno Martínez, Virtudes
Sadler, Peter
Marchán Sancho, Vicente
author_role author
author2 López-Senín, Paula
Salassa, Luca
Betanzos-Lara, Soledad
Habtemariam, Abraha
Moreno Martínez, Virtudes
Sadler, Peter
Marchán Sancho, Vicente
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Quimioteràpia del càncer
Pèptids
Ruteni
Oligonucleòtids
Receptors cel·lulars
Cancer chemotherapy
Peptides
Ruthenium
Oligonucleotides
Cell receptors
topic Quimioteràpia del càncer
Pèptids
Ruteni
Oligonucleòtids
Receptors cel·lulars
Cancer chemotherapy
Peptides
Ruthenium
Oligonucleotides
Cell receptors
description 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.
publishDate 2011
dc.date.none.fl_str_mv 2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/44124
url https://hdl.handle.net/2445/44124
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: http://dx.doi.org/10.1021/ja205235m
Journal of the American Chemical Society, 2011, vol. 133, num. 35, p. 14098-14108
http://dx.doi.org/10.1021/ja205235m
info:eu-repo/grantAgreement/EC/FP7/220281
info:eu-repo/grantAgreement/EC/FP7/247450
dc.rights.none.fl_str_mv (c) American Chemical Society , 2011
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Chemical Society , 2011
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420265605169152
score 15.300719

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