Download MendeleyInosine Can Increase DNA's Susceptibility to Photo-oxidation by a Ru(II) Complex due to Structural Change in the Minor Groove.
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.(2017) Chemistry 23: 10344-10351
- PubMed: 28543779
- DOI: https://doi.org/10.1002/chem.201701447
- Primary Citation of Related Structures:
4QIO, 5ET2 - PubMed 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{T 1 C 2 G 3 G 4 C 5 G 6 C 7 C 8 G 9 A 10 } 2 (G9) or d{TCGGCGCCIA} 2 (I9), the X-ray crystal structures show the dppz intercalated at the terminal T 1 C 2 ;G 9 A 10 step or T 1 C 2 ;I 9 A 10 step. Thus substitution of the G 9 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 NH 2 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 C 2 G 3 ;C 8 I 9 or T 2 G 3 ;C 8 A 9 steps, respectively, with G 3 the likely target for photo-oxidation. This demonstrates how changes in the minor groove (in this case removal of an NH 2 group) can facilitate binding of Ru II 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.
Organizational Affiliation:
Department of Chemistry, University of Reading, Whiteknights, Reading, RG6 6AD, UK.
