Inosine Can Increase DNA′s Susceptibility to Photo‐oxidation by a RuIIComplex due to Structural Change in the Minor Groove
| Autor: | Christine J. Cardin, Ian P. Clark, Sarah P. Gurung, Bjørn la Cour Poulsen, Fergus E. Poynton, Michael Towrie, James P. Hall, Susan J. Quinn, Páraic M. Keane, Igor V. Sazanovich, Thorfinnur Gunnlaugsson, John M. Kelly |
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| Rok vydání: | 2017 |
| Předmět: |
Guanine
Binding sites Coordination complexes Intercalation (chemistry) chemistry.chemical_element Crystal structure 010402 general chemistry Photochemistry 01 natural sciences Ruthenium Catalysis Nucleobase Electron transfer chemistry.chemical_compound Photochemical oxidants Ultraviolet spectrophotometry medicine Binding site Inosine Base Sequence 010405 organic chemistry Electron transport Organic Chemistry Fourier transform infrared spectroscopy Stereoisomerism DNA General Chemistry Structure-activity relationship Oxidation-reduction 0104 chemical sciences chemistry Intercalating agents Thermodynamics medicine.drug |
| Zdroj: | Chemistry – A European Journal. 23:10344-10351 |
| ISSN: | 1521-3765 0947-6539 |
| Popis: | 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. Irish Research Council Science Foundation Ireland University College Dublin Biotechnology and Biological Sciences Research Council Royal Irish Academy/Royal Society |
| Databáze: | OpenAIRE |
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