Inosine Can Increase DNA's Susceptibility to Photo-oxidation by a RuII Complex due to Structural Change in the Minor Groove
File Type:
PDFItem Type:
Journal ArticleDate:
2017Access:
openAccessCitation:
Keane P.M, Hall J.P, Poynton F.E, Poulsen B.C, Gurung S.P, Clark I.P, Sazanovich I.V, Towrie M, Gunnlaugsson T, Quinn S.J, Cardin C.J, Kelly J.M, Inosine Can Increase DNA's Susceptibility to Photo-oxidation by a RuII Complex due to Structural Change in the Minor Groove, Chemistry - A European Journal, 23, 43, 2017, 10344-10351Download Item:
Abstract:
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{T1 C2 G3 G4 C5 G6 C7 C8 G9 A10 }2 (G9) or d{TCGGCGCCIA}2 (I9), the X-ray crystal structures show the dppz intercalated at the terminal T1 C2 ;G9 A10 step or T1 C2 ;I9 A10 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 C2 G3 ;C8 I9 or T2 G3 ;C8 A9 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 RuII dppz 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.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
13/IA/1865
Science Foundation Ireland (SFI)
10/IN.1/B2999
Author's Homepage:
http://people.tcd.ie/gunnlauthttp://people.tcd.ie/jmkelly
Description:
PUBLISHED
Author: Gunnlaugsson, Thorfinnur; Kelly, John
Type of material:
Journal ArticleCollections
Series/Report no:
Chemistry - A European Journal23
43
Availability:
Full text availableKeywords:
DNA, Electron transfer, Inosine, Minor groove, Photooxidation, RutheniumDOI:
http://dx.doi.org/10.1002/chem.201701447Metadata
Show full item recordLicences: