Inosine Can Increase DNA′s Susceptibility to Photo‐oxidation by a RuII Complex due to Structural Change in the Minor Groove

DC FieldValueLanguage
dc.contributor.authorKeane, Páraic M.-
dc.contributor.authorHall, James P.-
dc.contributor.authorPoynton, Fergus E.-
dc.contributor.authorQuinn, Susan J.-
dc.contributor.authoret al.-
dc.date.accessioned2020-09-30T16:58:26Z-
dc.date.available2020-09-30T16:58:26Z-
dc.date.copyright2017 Wileyen_US
dc.date.issued2017-08-01-
dc.identifier.citationChemistry - A European Journalen_US
dc.identifier.issn0947-6539-
dc.identifier.urihttp://hdl.handle.net/10197/11614-
dc.description.abstractWeinheim Key to the development of DNA-targeting phototherapeutic drugs is determining the interplay between the photoactivity of the drug and its binding preference for a target sequence. For the photo-oxidising lambda-[Ru(TAP)2(dppz)]2+ (Λ-1) (dppz=dipyridophenazine) complex bound to either d{T1C2G3G4C5G6C7C8G9A10}2 (G9) or d{TCGGCGCCIA}2 (I9), the X-ray crystal structures show the dppz intercalated at the terminal T1C2;G9A10 step or T1C2;I9A10 step. Thus substitution of the G9 nucleobase by inosine does not affect intercalation in the solid state although with I9 the dppz is more deeply inserted. In solution it is found that the extent of guanine photo-oxidation, and the rate of back electron-transfer, as determined by pico- and nanosecond time-resolved infrared and transient visible absorption spectroscopy, is enhanced in I9, despite it containing the less oxidisable inosine. This is attributed to the nature of the binding in the minor groove due to the absence of an NH2 group. Similar behaviour and the same binding site in the crystal are found for d{TTGGCGCCAA}2 (A9). In solution, we propose that intercalation occurs at the C2G3;C8I9 or T2G3;C8A9 steps, respectively, with G3 the likely target for photo-oxidation. This demonstrates how changes in the minor groove (in this case removal of an NH2 group) can facilitate binding of RuIIdppz complexes and hence influence any sensitised reactions occurring at these sites. No similar enhancement of photooxidation on binding to I9 is found for the delta enantiomer.en_US
dc.description.sponsorshipIrish Research Councilen_US
dc.description.sponsorshipScience Foundation Irelanden_US
dc.description.sponsorshipUniversity College Dublinen_US
dc.format.mediumPrint-Electronic-
dc.language.isoenen_US
dc.publisherWileyen_US
dc.rightsThis is the peer reviewed version of the following article: P. M. Keane, J. P. Hall, F. E. Poynton, B. C. Poulsen, S. P. Gurung, I. P. Clark, I. V. Sazanovich, M. Towrie, T. Gunnlaugsson, S. J. Quinn, C. J. Cardin, J. M. Kelly, Chem. Eur. J. 2017, 23, 10344-10351., which has been published in final form at https://doi.org/10.1002/chem.201701447. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.en_US
dc.subjectRutheniumen_US
dc.subjectGuanineen_US
dc.subjectDNAen_US
dc.subjectInosineen_US
dc.subjectIntercalating agentsen_US
dc.subjectPhotochemical oxidantsen_US
dc.subjectFourier transform infrared spectroscopyen_US
dc.subjectUltraviolet spectrophotometryen_US
dc.subjectBinding sitesen_US
dc.subjectBase Sequenceen_US
dc.subjectStructure-activity relationshipen_US
dc.subjectElectron transporten_US
dc.subjectOxidation-reductionen_US
dc.subjectStereoisomerismen_US
dc.subjectThermodynamicsen_US
dc.subjectCoordination complexesen_US
dc.titleInosine Can Increase DNA′s Susceptibility to Photo‐oxidation by a RuII Complex due to Structural Change in the Minor Grooveen_US
dc.typeJournal Articleen_US
dc.internal.authorcontactothersusan.quinn@ucd.ieen_US
dc.statusPeer revieweden_US
dc.identifier.volume23en_US
dc.identifier.issue43en_US
dc.identifier.startpage10344en_US
dc.identifier.endpage10351en_US
dc.identifier.doi10.1002/chem.201701447-
dc.neeo.contributorKeane|Páraic M.|aut|-
dc.neeo.contributorHall|James P.|aut|-
dc.neeo.contributorPoynton|Fergus E.|aut|-
dc.neeo.contributorQuinn|Susan J.|aut|-
dc.neeo.contributoret al.||aut|-
dc.description.othersponsorshipBiotechnology and Biological Sciences Research Councilen_US
dc.description.othersponsorshipRoyal Irish Academy/Royal Societyen_US
dc.date.updated2020-09-21T14:31:05Z-
dc.identifier.grantidBB/M004635/1-
dc.identifier.grantid10/IN.1/B2999-
dc.identifier.grantid13/IA/1865-
dc.rights.licensehttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/en
item.fulltextWith Fulltext-
item.grantfulltextopen-
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