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

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Title: Inosine Can Increase DNA′s Susceptibility to Photo‐oxidation by a RuII Complex due to Structural Change in the Minor Groove
Authors: Keane, Páraic M.Hall, James P.Poynton, Fergus E.Quinn, Susan al.
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Date: 1-Aug-2017
Online since: 2020-09-30T16:58:26Z
Abstract: Weinheim 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.
Funding Details: Irish Research Council
Science Foundation Ireland
University College Dublin
Funding Details: Biotechnology and Biological Sciences Research Council
Royal Irish Academy/Royal Society
Type of material: Journal Article
Publisher: Wiley
Journal: Chemistry - A European Journal
Volume: 23
Issue: 43
Start page: 10344
End page: 10351
Copyright (published version): 2017 Wiley
Keywords: RutheniumGuanineDNAInosineIntercalating agentsPhotochemical oxidantsFourier transform infrared spectroscopyUltraviolet spectrophotometryBinding sitesBase SequenceStructure-activity relationshipElectron transportOxidation-reductionStereoisomerismThermodynamicsCoordination complexes
DOI: 10.1002/chem.201701447
Language: en
Status of Item: Peer reviewed
ISSN: 0947-6539
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Appears in Collections:Chemistry Research Collection

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