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Inosine 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., Poulson, B. C., Gurung, S. P., Clark, I. P., Sazanovich, I. V., Towrie, M., Gunnlaugsson, T., Quinn, S. J., Cardin, C. J. and Kelly, J. M. (2017) Inosine can increase DNA's susceptibility to photo-oxidation by a Ru(II) complex due to structural change in the minor groove. Chemistry - A European Journal, 23 (43). pp. 10344-10351. ISSN 0947-6539

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To link to this item DOI: 10.1002/chem.201701447

Abstract/Summary

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+ (Ʌ-1) complex bound to either d{T1C2G3G4C5G6C7C8G9A10}2 (G9) or d{TCGGCGCCIA}2 (I9), the X- ray crystal structures shows 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 ps and ns 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 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.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
ID Code:70524
Publisher:Wiley-V C H Verlag GMBH

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